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Sample records for first-line restaging modality

  1. Modality

    DEFF Research Database (Denmark)

    Klinge, Alex; Müller, Henrik Høeg

    Modality: Studies in Form and Function reflects the diversity of theoretical frameworks and the heterogeneity of linguistic phenomena under the general heading of modality. Researchers in the fields of logic, philosophy and linguistics have for many years been pondering the elusive nature...

  2. FDG PET scan strategies and long-term outcomes after first-line therapy in Hodgkin's Disease

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    Poulou, Loukia S. [Department of Computed Tomography, ' Sotiria' General Hospital for Chest Diseases, Athens (Greece); Karianakis, George [Bone Marrow Transplantation Unit, ' Hygeia' Diagnostic and Therapeutic Centre, 4 Erythrou Stavrou Street, 151 23 Athens (Greece); Ziakas, Panayiotis D. [Bone Marrow Transplantation Unit, ' Hygeia' Diagnostic and Therapeutic Centre, 4 Erythrou Stavrou Street, 151 23 Athens (Greece)], E-mail: zpanos@otenet.gr

    2009-06-15

    Background: The use of positron emission tomography with fluoro-deoxy-glucose (FDG PET) in Hodgkin's disease (HD) is continuing to expand worldwide, with response assessment after completion of therapy being its most widely utilized application. A positive scan has been associated with high relapse rates and disease progression. Methods: A decision analysis was performed to determine the long-term impact of FDG PET restaging both with and without computed tomography (CT) in terms of the 5-year progression-free survival (5yrPFS). Outcomes and utilities were based on published data. The first strategy involved CT restaging after first-line therapy, with or without subsequent FDG PET, while Second strategy used FDG PET scan alone. All positive test required histological examination. Upon histological confirmation of active lymphoma, patients were considered candidates for autologous transplantation and long-term outcomes were retrieved. The expected clinical benefit of the two strategies was calculated and depicted, along with the mean costs. One-way and two-way sensitivity analyses were performed to ensure the validity of the results. Results: CT restaging plus FDG PET when residual mass is detected, results in a 2% benefit at 5yrPFS at baseline compared to FDG PET-alone restaging and remains positive for a wide range of probabilities. This strategy reduces the average cost by Euro 1863 per patient, including costs of biopsy and autologous transplantation. Conclusion: A more conservative approach that includes CT restaging after first-line therapy and FDG PET scan only on residual mass, is the preferred strategy in HD. Furthermore it appears to confer the maximal diagnostic yield along with a substantial reduction in the mean cost.

  3. Managing first-line failure.

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    Cooper, David A

    2014-01-01

    WHO standard of care for failure of a first regimen, usually 2N(t)RTI's and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(t)RTI's. Until recently, there was no evidence to support these recommendations which were based on expert opinion. Two large randomized clinical trials, SECOND LINE and EARNEST both showed excellent response rates (>80%) for the WHO standard of care and indicated that a novel regimen of a boosted protease inhibitor with an integrase inhibitor had equal efficacy with no difference in toxicity. In EARNEST, a third arm consisting of induction with the combined protease and integrase inhibitor followed by protease inhibitor monotherapy maintenance was inferior and led to substantial (20%) protease inhibitor resistance. These studies confirm the validity of the current recommendations of WHO and point to a novel public health approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those failing first-line treatments. Protease inhibitor monotherapy is not suitable for a public health approach in low- and middle-income countries.

  4. Managing first-line failure

    Directory of Open Access Journals (Sweden)

    David A Cooper

    2014-11-01

    Full Text Available WHO standard of care for failure of a first regimen, usually 2N(tRTI's and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(tRTI's. Until recently, there was no evidence to support these recommendations which were based on expert opinion. Two large randomized clinical trials, SECOND LINE and EARNEST both showed excellent response rates (>80% for the WHO standard of care and indicated that a novel regimen of a boosted protease inhibitor with an integrase inhibitor had equal efficacy with no difference in toxicity. In EARNEST, a third arm consisting of induction with the combined protease and integrase inhibitor followed by protease inhibitor monotherapy maintenance was inferior and led to substantial (20% protease inhibitor resistance. These studies confirm the validity of the current recommendations of WHO and point to a novel public health approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those failing first-line treatments. Protease inhibitor monotherapy is not suitable for a public health approach in low- and middle-income countries.

  5. First line management in the public sector

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    Voxted, Søren

    The paper will examines and discusses the results from a structured observational study, wherein 50 first-line managers from the public sector in Denmark in five areas of employment where observed. These observational studies are a key contribution in the ‘greenhouse for management’ project......, the study explores which tasks the managers primarily perform, divided into eight categories of activities. Third, it is examined how the manager’s usage of time is divided among the individual tasks. The results of the above data can be used both to provide a comprehensive characterization of municipal...... first-line managers’ work and to illuminate differences between first-line managers from different occupational groups. The second question relates to current debate about the degree of professionalized management among the municipal first-line managers. In both the international and Danish management...

  6. Prognostic value of interim and restaging PET/CT in Hodgkin lymphoma. Results of the CHEAP (Chemotherapy Effectiveness Assessment by PET/CT) study - long term observation.

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    Miltenyi, Z; Barna, S; Garai, I; Simon, Z; Jona, A; Magyari, F; Gergely, M; Nagy, Z; Keresztes, K; Pettendi, P; Illes, A

    2015-01-01

    Very few studies have determined the prognostic value of interim and restaging PET/CT in patients with Hodgkin lymphoma using current standard of care therapy outside clinical trials. We analyzed the effect of the results of interim and restaging PET/CT on the survival (overall- and relapse-free) in patients who received standard first-line treatment based on the stage of disease and risk factors. We investigated the differences between the relapse and non-relapse groups based on the clinical pathological characteristics of patients who had positive interim PET/CT results.Between January 1, 2007 and December 31, 2011, the staging, interim and restaging PET/CT scans of patients with Hodgkin lymphoma were analyzed. The Deauville criteria were used for the evaluation of interim PET/CT scans. One hundred and thirteen Hodgkin lymphoma patients underwent staging, interim and restaging PET/CT scans. None of the therapy was modified based on the interim PET/CT results. The median follow-up time was 43.5 months. A total of 62 early stage patients and 51 advanced stage patients were identified. The five-year overall survival rates were 93.4% in the interim PET negative group and 58% in the interim PET positive group (pinterim PET positive group, patients over 40 years of age had a significantly higher probability of relapse (p=0.057).The routine clinical use of interim PET/CT is highly recommended based on our investigation. However, patients with positive interim PET/CT results required frequent additional evaluations.

  7. Moving Shadows, Moving Sun. Early Modem Sundials Restaging Miracles.

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    Mersmann, Jasmin

    2015-01-01

    Irrespective of geo- or heliocentric presuppositions, the functioning of sundials is based on the observation of moving shadows or light spots. Even though the cast shadow was often simply used to indicate the time, it could also remind the users of the ephemerality of earthly things or function as an index of planetary movements. This article examines the various ways in which early modem sundials visually interpret the moving shadow or light spot. The instruments address the shadow in inscriptions, integrate it into their design (e.g., in cruciform dials) or even manipulate its course (as in the so-called Horologium Ahaz). Both the crucifix and the Ahaz dials not only refer to astronomical miracles but actually restage them. Even though by means of the horologium it was not possible to explain the Old Testament miracle of the shadow moving backward, adepts were able to recreate it on a terrestrial scale.

  8. Is diagnostic accuracy of 18F - FDG PET/CT different according to anatomical levels of cervical lymph node in restaging of papillary thyroid cancer?

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    Ha, J. M.; Kwon, S. Y.; Seo, Y. S.; Chong, A. R.; Jeong, S. Y.; Jeong, Y. Y.; Min, J. J.; Song, H. C.; Bom, H. S. [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2007-07-01

    To restage of thyroid papillary cancer, accurate detection of metastatic cervical lymph node (LN) is important. Therefore, we assessed the diagnostic accuracy of restaging 18F-FDG PET/CT according to anatomical levels of cervical LN. Thirty patients (F 19, M 11, mean age 49.2 y) with total thyroidectomy and regional LN dissection were included for restaging thyroid papillary carcinoma. We analyzed lymph node metastases according to anatomical level by AJCC 1996. Sixty nine LNs from these patients were analyzed by comparing PET/CT results with surgical pathology. We determined the cut-off value as maxSUV = 3.0 using ROC curve analysis. Overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of PET/CT was 81.1%, 59.4%, 69.8%, 73.1% and 71.1%, respectively. In each LN levels, level II showed 72.7%, 50%, 44.4%, 76.9%, 58%, level III 100%, 50%, 90%, 100%, 90.9%, level IV, 80%, 66.7%, 88.9%, 50%, 77%, level V 100%, 66.7%, 75%, 100%, 83.3%. Level I showed specificity of 100%, NPV of 80%, diagnostic accuracy of 80%. Level VI showed sensitivity of 100%, PPV of 100%, diagnostic accuracy of 100%. Out of total 14 false-positive, 10 was located in level II. There was no significant difference of maxSUV between benign and malignant lesion in level II LN group (p>0.05). But there were significant difference of maxSUV in other LN levels (p<0.01). PET/CT was useful for detecting metastatic or recurred cervical LNs in restaging of thyroid papillary cancer. However, because there can be many false-positive lesions in level II as compared to other levels, we need to apply different cut-off value of FDG uptake or consider other imaging modalities when we evaluate level II LNs.

  9. Endobronchial ultrasound with transbronchial needle aspiration for restaging the mediastinum in lung cancer

    DEFF Research Database (Denmark)

    Herth, F.J.F.; Annema, J.T.; Eberhardt, R.

    2008-01-01

    Purpose To investigate the sensitivity and accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for restaging the mediastinum after induction chemotherapy in patients with non-small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty......-four consecutive patients with tissue-proven stage IIIA-N2 disease who were treated with induction chemotherapy and who had undergone mediastinal restaging by EBUS-TBNA were reviewed. On the basis of computed tomography, 58 patients were classified as having stable disease and 66 were judged to have had a partial......-TBNA for mediastinal restaging after induction chemotherapy were 76%, 100%, 100%, 20%, and 77%, respectively. Conclusion EBUS-TBNA is a sensitive, specific, accurate, and minimally invasive test for mediastinal restaging of patients with NSCLC. However, because of the low negative predictive value, tumor...

  10. New modalities (setting, fractionation) of radioimmunotherapy by {sup 90}Y-ibritumomab tiuxetan ({sup 90}Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach; Nouvelles modalites (consolidation, fractionnement) de radioimmunotherapie par {sup 90}Y-ibritumomab tiuxetan (Zevalin) en traitement de premiere ligne des lymphomes malin non hodgkiniens de type folliculaire: efficacite, toxicite et approche dosimetrique personnalisee

    Energy Technology Data Exchange (ETDEWEB)

    Morschhauser, F

    2008-12-15

    Rationale: radioimmunotherapy (R.I.T.) with {sup 90}Y-ibritumomab tiuxetan ([{sup 90}Y] Zevalin ) is a new treatment option for patients with relapsed/refractory non Hodgkin follicular lymphoma (F.L.). Efficacy increases when Zevalin is used earlier in the disease course. Currently, Zevalin dosage is based on weight and not dosimetry. This most likely results in a wide range of absorbed dose to critical organs and tumor, which in turn translates in unpredictable efficacy and toxicity. Optimizing R.I.T. with [{sup 90}Y] Zevalin will require its use as part of first-line therapy and implementation of patient-specific dosimetry methods in clinical trials. Objectives and methods: we have consecutively studied 2 new modalities of using Zevalin in first line therapy of F.L.. First, we conducted an international, randomized, phase 3 trial to evaluate the efficacy and safety of consolidation with Zevalin(15 MBq/Kg) in patients with advanced-stage F.L. achieving at least a partial response after induction immuno chemotherapy. A second approach consisted of evaluating a fractionated schedule with 2 doses of Zevalin (11.1 MBq/kg each), 9 to 13 weeks apart, as front line therapy in F.L. patients with high tumor burden. As part of this second approach, we designed a refined imaging-based (planar and 3-dimensional) dosimetry protocol to improve prediction of dose efficacy and toxicity after each dose of zevalin. Data acquisition was performed in 3 centers (Lille, Nantes and Manchester) while data treatment and specific dose calculations for major organ, tumor masses and bone marrow were centralized. Conclusion: Consolidation of first remission with {sup 90}Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging P.F.S. by 2 years and resulting in high P.R.-to-C.R. conversion rates regardless of type of first-line induction treatment. Preliminary data show the feasibility of front line fractionated R.I.T. with

  11. First Line Treatment of Meniere’s Disease

    OpenAIRE

    Anup Acharya; Madan Mohan Singh; Arati Shrestha

    2016-01-01

    Introduction: There is no consensus on the first line medical treatment of Meniere disease to produce symptomatic improvement and slow the disease progress. Dietary salt restriction, diuretics, and vasodilators like betahistine are among the first line drugs that have been used for long. There is lack of evidence due to paucity of quality studies to support their effectiveness and advocate their use. This study is done to evaluate the effectiveness of three first line treatment of Meniere dis...

  12. Local Methotrexate Injection as the First-line Treatment for Cesarean Scar Pregnancy: Review of the Literature.

    Science.gov (United States)

    Cheung, Vincent Y T

    2015-01-01

    The objective of this study was to determine the outcome of using ultrasound-guided local methotrexate injection as the first-line treatment of cesarean scar pregnancy (CSP). A literature review was performed on all eligible reports using this modality as the first-line treatment of CSP. Relevant publications were obtained from the PubMed electronic database from inception to December 2014. Ninety-six cases from 95 women reported in 17 articles were reviewed. The success rate was 73.9% after a single local methotrexate injection. An accumulated success rate of 88.5% could be achieved after additional local or intramuscular methotrexate administration. Eleven cases (11.5%) failed methotrexate treatment and required surgical interventions. Except for women with serum human chorionic gonadotropin levels higher than 100 000 IU/L, ultrasound-guided local methotrexate injection could be considered as a first-line treatment modality for CSP.

  13. PET/CT: First-Line Examination to Assess Disease Extent of Disseminated Coccidioidomycosis.

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    Foerter, Jason; Sundell, John; Vroman, Penny

    2016-09-01

    Coccidioidomycosis is an infection caused by inhalation of the Coccidioides fungus. Most infections remain subclinical or are confined to the pulmonary system. Disseminated disease is rare. Traditionally, a combination of imaging modalities has been used to determine disease extent. We suggest (18)F-FDG PET/CT as a single first-line imaging examination to assess disease extent. We present a case of disseminated coccidioidomycosis to the lung, mediastinum, soft tissues, and skeletal system. To our knowledge, no prior case reports demonstrate such widespread disease using PET/CT. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Diagnostic value of PET/CT for the staging and restaging of pediatric tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kleis, Margit [University of California (UCSF), Department of Radiology, San Francisco, CA (United States)]|[Technical University of Munich, Department of Radiology, Munich (Germany); Daldrup-Link, Heike; Lu, Ying; Schreck, Carole; Chu, Philip W.; Hawkins, Randall A.; Franc, Benjamin L. [University of California (UCSF), Department of Radiology, San Francisco, CA (United States); Matthay, Katherine [University of California, Department of Pediatrics, Division of Pediatric Hemato-Oncology, San Francisco, CA (United States); Goldsby, Robert [University of California, Department of Pediatric Oncology, San Francisco, CA (United States); Schuster, Tibor [Technical University of Munich, Department of Biostatistics and Epidemiology, Munich (Germany)

    2009-01-15

    The objective of this retrospective study was to compare the diagnostic value of 2-[{sup 18}F]fluoro-2-deoxy-d-glucose positron emission tomography ({sup 18}F-FDG PET)/CT versus {sup 18}F-FDG PET and CT alone for staging and restaging of pediatric solid tumors. Forty-three children and adolescents (19 females and 24 males; mean age, 15.2 years; age range, 6-20 years) with osteosarcoma (n = 1), squamous cell carcinoma (n = 1), synovial sarcoma (n = 2), germ cell tumor (n = 2), neuroblastoma (n = 2), desmoid tumor (n = 2), melanoma (n = 3), rhabdomyosarcoma (n = 5), Hodgkin's lymphoma (n = 7), non-Hodgkin-lymphoma (n = 9), and Ewing's sarcoma (n = 9) who had undergone {sup 18}F-FDG PET/CT imaging for primary staging or follow-up of metastases were included in this study. The presence, location, and size of primary tumors was determined separately for PET/CT, PET, and CT by two experienced reviewers. The diagnosis of the primary tumor was confirmed by histopathology. The presence or absence of metastases was confirmed by histopathology (n = 62) or clinical and imaging follow-up (n = 238). The sensitivities for the detection of solid primary tumors using integrated {sup 18}F-FDG PET/CT (95%), {sup 18}F-FDG PET alone (73%), and CT alone (93%) were not significantly different (p > 0.05). Seventeen patients showed a total of 153 distant metastases. Integrated PET/CT had a significantly higher sensitivity for the detection of these metastases (91%) than PET alone (37%; p < 0.05), but not CT alone (83%; p > 0.05). When lesions with a diameter of less than 0.5 cm were excluded, PET/CT (89%) showed a significantly higher specificity compared to PET (45%; p < 0.05) and CT (55%; p < 0.05). In a sub-analysis of pulmonary metastases, the values for sensitivity and specificity were 90%, 14%, 82% and 63%, 78%, 65%, respectively, for integrated PET/CT, stand-alone PET, and stand-alone CT. For the detection of regional lymph node metastases, {sup 18}F-FDG PET/CT, {sup 18}F

  15. Role of {sup 18F} FDG PET/CT, {sup 123I} MIBG SPECT, and CT in Restaging patients Affected by Malignant Pheochromocytoma

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    Cantalamessa, Antonio; Caobelli, Antonio; Vavassori, Francesca [Habilita Istituto Clinico, Bergamo (Italy); Caobelli, Federico [Univ. of Brescia, Brescia (Italy); Paghera, Barbara [Spedali Civili, Brescia (Italy)

    2011-06-15

    Pheochromocytoma (PH) is a rare catecholamine secreting tumor that arises from chromaffin tissue within the adrenal medulla and extra adrenal sites; commonly it is sporadic, and malignant PH accounts for about 10% of all cases. Several imaging modalities have been used for the diagnosis and staging og this tumor: functional imaging using radio labelled metaiodobenzylguanidine and, more recently, {sup 18F} fluorodeoxyglucose positron emission tomography ({sup 18F} FDG PET/CT), which offers substantial sensitivity and specificity to correctly detect metastatic PH and helps to identify patients suitable for treatment with radiopharmaceuticals. The aim of our study was to compare CT, {sup 18F} FDG PET/CT, and {sup 123I} metaiodobenzylguanidine single photon emission tomography ({sup 123I} MIBG SPECT) as feasible methods to restage patients diagnosed histologically with PH. We retrospectively evaluated 38 patients (27 females and 11 males; mean age: 44{+-}15 years) with malignant PH documented histologically after surgical intervention. These patients underwent CT, {sup 18F} FDG PET/CT, and {sup 123I} MIBG SPECT. {sup 18F} FDG PET/CT showed positive results for neoplastic tissue in 33/38 patients (86.8%) and negative in 5/38 (13.2%), in concordance with CT alone. {sup 123I} MIBG SPECT was positive in 30/38 patients (78.9%) and negative in 8/38 (21.1%). No differences in lesion numbers were found between {sup 18F} FDG PET/CT and {sup 123I} MIBG SPECT. {sup 18F} FDG PET/CT could more accurately restage patients with PH than CT and {sup 123I} MIBG SPECT, also in the absence of a staging study.

  16. Bilingual Cancer Information: Access Is the First Line of Defense

    Science.gov (United States)

    Boudreault, Patrick; Palmer, Christina

    2015-01-01

    Information about cancer, the disease that kills more Americans than any other except heart disease, is essential. In some ways, information is our first line of defense. It allows us to identify individual risk factors, to note when a problem means we should see a professional, and to avoid activities that might put us at risk. However,…

  17. The role of MRI with diffusion-weighted imaging in restaging rectal cancers after neoadjuvant chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Irem Bayram

    2016-03-01

    Full Text Available Background: It is challenging to restage rectal cancer at MRI, in patients who have had neoadjuvant chemoradiotherapy.Objective: To investigate the accuracy of MRI with diffusion-weighted imaging (DWI in the restaging of rectal cancer.Materials and methods: Pre- and post-neoadjuvant chemoradiotherapy MRI examinations of 35 patients diagnosed with locally advanced rectal cancer were evaluated and subsequently compared with post-operative pathology results.Results: The accuracy of MRI with DWI to determine the T-stage status was calculated as 54.28%. Kappa statistics revealed poor concordance with pathology results, with a κ value of 0.212 ± 0.114 (p = 0.028. The apparent diffusion coefficient (ADC values measured after the neoadjuvant chemotherapy revealed a significant increase when compared with pre-treatment ADC values (p < 0.000001. MRI accuracy rate for lymph node involvement was calculated as 57.14% with a κ value of 0.001 (p = 0.989. MRI had 80% sensitivity and 100% specificity in determining mesorectal fascia involvement, with a calculated positive predictive value of 100% and a calculated negative predictive value of 96%. The accuracy of MRI in overall staging according to the TNM staging system was 28%.Conclusion: The accuracy of MRI in restaging rectal cancer is not yet sufficient and is not on par with the accuracy of MRI in the primary staging of the disease. This is attributed to post-treatment changes. Adding DWI to the protocol is promising, but more expanded data are required.

  18. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension.

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    Xue, Hao; Lu, Zhuang; Tang, Wen Lu; Pang, Lu Wei; Wang, Gan Mi; Wong, Gavin W K; Wright, James M

    2015-01-11

    Renin-angiotensin system (RAS) inhibitors are widely prescribed for treatment of hypertension, especially for diabetic patients on the basis of postulated advantages for the reduction of diabetic nephropathy and cardiovascular morbidity and mortality. Despite widespread use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for hypertension in both diabetic and non-diabetic patients, the efficacy and safety of RAS inhibitors compared to other antihypertensive drug classes remains unclear. To evaluate the benefits and harms of first-line RAS inhibitors compared to other first-line antihypertensive drugs in patients with hypertension. We searched the Cochrane Hypertension Group's Specialised Register, MEDLINE, MEDLINE In-Process, EMBASE and ClinicalTrials.gov for randomized controlled trials up to November 19, 2014 and the Cochrane Central Register of Controlled Trials (CENTRAL) up to October 19, 2014. The WHO International Clinical Trials Registry Platform (ICTRP) is searched for inclusion in the Cochrane Hypertension Group's Specialised Register. We included randomized, active-controlled, double-blinded studies with at least six months follow-up in people with primary elevated blood pressure (≥130/85 mmHg), which compared first-line RAS inhibitors with other first-line antihypertensive drug classes and reported morbidity and mortality or blood pressure outcomes. Patients with proven secondary hypertension were excluded. Two authors independently selected the included trials, evaluated the risk of bias and entered the data for analysis. We included 42 studies, involving 65,733 participants, with a mean age of 66 years. Much of the evidence for our key outcomes is dominated by a small number of large studies at a low risk of bias for most sources of bias. Imbalances in the added second-line antihypertensive drugs in some of the studies were important enough for us to downgrade the quality of the evidence.Primary outcomes were

  19. First Line Treatment of Meniere’s Disease

    Directory of Open Access Journals (Sweden)

    Anup Acharya

    2016-12-01

    Full Text Available Introduction: There is no consensus on the first line medical treatment of Meniere disease to produce symptomatic improvement and slow the disease progress. Dietary salt restriction, diuretics, and vasodilators like betahistine are among the first line drugs that have been used for long. There is lack of evidence due to paucity of quality studies to support their effectiveness and advocate their use. This study is done to evaluate the effectiveness of three first line treatment of Meniere disease i.e. salt restriction, oral diuretics, and betahistine.   Methods: Double blind randomized controlled trial was carried out in out-patient clinic of Ear Nose and Throat department of Lumbini Medical College Teaching Hospital. Cases were randomized into three groups; dietary salt restriction, diuretics as amiloride and furosemide, and vasodilator as betahistine. Pre and post treatment evaluation was done in terms of number and severity of vertigo, tinnitus, and hearing outcome.   Results: There were a total of 97 cases with F:M ratio of 1.1:1. Mean age of patients was 47.86 yr (SD=12.7. Twenty-nine (30% were treated with dietary sodium restriction alone (Group A, 35 (36% were treated with diuretics (Group B and the rest 33 (34% were treated with vasodilator (betahistine, Group C. There was no significant difference in hearing outcome in any group. Tinnitus was significantly improved in Group B. Number of vertigo attack was significantly decreased in Group B and Group C. Severity of vertigo was significantly decreased in Group B.   Conclusion: Dietary salt restriction alone was not effective in controlling any aspect of the disease whereas diuretics were effective in reducing tinnitus and number and severity of vertigo. Betahistine was effective in reducing the number of vertigo attacks but not effective on other aspects of the disease.

  20. First-Line Treatment of Metastatic Pancreatic Cancer

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    Mohammed Tokh

    2012-03-01

    Full Text Available Metastatic pancreatic cancer is an aggressive malignancy that is difficult to treat. Gemcitabine monotherapy has been used first line and many contemporary treatment approaches have focused on gemcitabine plus experimental agents. The 2012 ASCO Gastrointestinal Cancers Symposium Abstract #213 is a study of gemcitabine with IPI-926, a novel hedgehog pathway inhibitor. Abstract #227 is a study of gemcitabine with 90Y-hPAM4 radioimmunotherapy with yttrium labeled anti-mucin humanized antibody. Abstract #296 is a study of gemcitabine with temsirolimus, an mTOR inhibitor. Gemcitabine and erlotinib has shown slight advantages to gemcitabine alone. Abstract #253 takes this one step further and evaluates gemcitabine and erlotinib with apricoxib, a COX-2 inhibitor. FOLFIRINOX has shown superiority to gemcitabine; however, doing so at the cost of significantly greater toxicity. Abstract #199, is a study which examines the cost effectiveness of first line FOLFIRINOX approaches. Another cost effective study is portrayed in Abstract #372, a study evaluating the survival of unresectable pancreatic cancer patients treated with gemcitabine and the disease course is followed clinically without radiographic follow-up.

  1. First-line antiretroviral drug discontinuations in children

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    Fortuin-de Smidt, Melony; de Waal, Reneé; Cohen, Karen; Technau, Karl-Günter; Stinson, Kathryn; Maartens, Gary; Boulle, Andrew; Igumbor, Ehimario U.; Davies, Mary-Ann

    2017-01-01

    Introduction There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010. Methods We included children (<16 years at ART initiation) who initiated ≥3 antiretrovirals between 2004–2014 with ≥1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity. Results We included 3579 children with median follow-up duration of 41 months (IQR 14–72). At ART initiation, median age was 44 months (IQR 13–89) and median CD4 percent was 15% (IQR 9–21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2–55.4), 1.6 (0.5–4.8), 2.0 (1.2–3.3), and 1.3 (0.6–2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively. Conclusions While stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health

  2. Diagnostic value of combined {sup 18}F-FDG PET/MRI for staging and restaging in paediatric oncology

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    Pfluger, Thomas; Melzer, Henriette I.; Mueller, Wolfgang P.; Bartenstein, Peter [Ludwig Maximilians University of Munich, Department of Nuclear Medicine, Munich (Germany); Coppenrath, Eva [Ludwig Maximilians University of Munich, Department of Radiology, Munich (Germany); Albert, Michael H.; Schmid, Irene [Ludwig Maximilians University of Munich, Department of Paediatric Oncology/Haematology, Munich (Germany)

    2012-11-15

    The present study compares the diagnostic value of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and MRI to combined/registered {sup 18}F-FDG PET/MRI for staging and restaging in paediatric oncology. Over 8 years and 2 months, 270 {sup 18}F-FDG PET and 270 MRI examinations (mean interval 5 days) were performed in 132 patients with proven (n = 117) or suspected (n = 15) malignant disease: solid tumours (n = 64), systemic malignancy (n = 53) and benign disease (n = 15). A total of 259 suspected tumour lesions were analysed retrospectively during primary diagnosis and 554 lesions during follow-up. Image analysis was performed separately on each modality, followed by analysis of combined and registered {sup 18}F-FDG PET/MRI imaging. A total of 813 lesions were evaluated and confirmed by histopathology (n = 158) and/or imaging follow-up (n = 655) after 6 months. In the separate analysis of {sup 18}F-FDG PET and MRI, sensitivity was 86 %/94 % and specificity 85 %/38 %. Combined/registered {sup 18}F-FDG PET/MRI led to a sensitivity of 97 %/97 % and specificity of 81 %/82 %. False-positive results ({sup 18}F-FDG PET n = 69, MRI n = 281, combined {sup 18}F-FDG PET/MRI n = 85, registered {sup 18}F-FDG PET/MRI n = 80) were due to physiological uptake or post-therapeutic changes. False-negative results ({sup 18}F-FDG PET n = 50, MRI n = 20, combined {sup 18}F-FDG PET/MRI n = 11, registered {sup 18}F-FDG PET/MRI n = 11) were based on low uptake or minimal morphological changes. Examination-based evaluation during follow-up showed a sensitivity/specificity of 91 %/81 % for {sup 18}F-FDG PET, 93 %/30 % for MRI and 96 %/72 % for combined {sup 18}F-FDG PET/MRI. For the detection of single tumour lesions, registered {sup 18}F-FDG PET/MRI proved to be the methodology of choice for adequate tumour staging. In the examination-based evaluation, MRI alone performed better than {sup 18}F-FDG PET and combined/registered imaging during primary diagnosis. At follow

  3. First-line therapy in ovarian cancer trials.

    Science.gov (United States)

    Thigpen, Tate; duBois, Andreas; McAlpine, Jessica; DiSaia, Philip; Fujiwara, Keiichi; Hoskins, William; Kristensen, Gunnar; Mannel, Robert; Markman, Maurie; Pfisterer, Jacobus; Quinn, Michael; Reed, Nick; Swart, Ann Marie; Berek, Jonathan; Colombo, Nicoletta; Freyer, Gilles; Gallardo, Dolores; Plante, Marie; Poveda, Andres; Rubinstein, Lawrence; Bacon, Monica; Kitchener, Henry; Stuart, Gavin C E

    2011-05-01

    At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today?

  4. Considering tapentadol as a first-line analgesic: 14 questions.

    Science.gov (United States)

    Pergolizzi, Joseph V; Breve, Frank; Taylor, Robert; Raffa, Robert B; Strasburger, Stephani E; LeQuang, Jo Ann

    2017-07-01

    Tapentadol is the newest centrally acting analgesic to be approved by the US FDA and regulatory bodies in other countries. It has been called the first-in-class of a novel-acting analgesic mechanism of action that combines µ-opioid receptor agonist activity with neuronal norepinephrine-reuptake inhibition in a single molecule. This duality of action should combine inhibition of ascending (afferent) pain-transmitting signals with activation of descending (efferent) pain-attenuating systems (e.g., diffuse noxious inhibitory controls). However, not all novel mechanisms of action impart the characteristics needed for an analgesic to be considered for first-line therapy. These key questions may help inform clinical decision making.

  5. Pentoxifylline: A first line treatment option for severe alcoholic hepatitis and hepatorenal syndrome?

    Institute of Scientific and Technical Information of China (English)

    Stelios F Assimakopoulos; Konstantinos C Thomopoulos; Chrisoula Labropoulou-Karatza

    2009-01-01

    Although favourable results of pentoxifylline (PTX) used in treatment of severe alcoholic hepatitis patients with a Maddrey discriminant function score ≥ 32 have been previously reported, it is not currently recommended as a first line treatment for alcoholic hepatitis owing to lack of evidence for its efficacy as compared to the standard treatment with corticosteroids. In a very recent issue of World Journal of Gastroenterology, Dr. De BK and colleagues compared for the first time the two treatment modalities head to head in a randomized controlled study, demonstrating the advantage of PTX over corticosteroids in terms of patients' survival and risk-benefit profile. The advantage of PTX over corticosteroids in survival of patients with severe alcoholic hepatitis was found to be related to the prevention of hepatorenal syndrome in their study. This study raises the question of the use of PTX as a standard treatment for severe alcoholic hepatitis. Considering the fact that PTX presented a spectacular efficiency in prevention of hepatorenal syndrome in their study as well as that previous studies have shown that this effect is possibly related to a primary renoprotective action because it is irrelevant of tumor necrosis factor-α synthesis inhibition or improved liver function, we tempted to speculate that PXT might be an effective option for prevention and/or treatment of hepatorenal syndrome complicating other forms of advanced liver disease. This attractive theory remains to be elucidated by pressing future studies in view of the lack of effective treatment modalities for hepatorenal syndrome.

  6. What Modals Are: Modal Verbs, Modal Words, and Auxiliary Modals

    Directory of Open Access Journals (Sweden)

    Fazira A. Kakzhanova

    2013-01-01

    Full Text Available The modals are a complicated grammatical phenomenon. As of today, the status of modals is still not precisely defined in the linguistics literature, and they are described under different names: modal verbs, modal words, auxiliary modals, or defective verbs. Modals express the result of the conversion of thought processes (deep structure about the realization of actions into surface structure. As articles determine the status of nouns as indefinite or definite things, modals determine the relation of a person to actions or the quality of an action as realizable or unrealizable. Modals cannot truly be ‘modal verbs’, because they lack the morphological characteristics of verbs (aspect, voice, mood, and tense, and the term ‘defective verb’ is flawed for the same reason. Furthermore, they cannot be ‘auxiliary modals’, because they don’t neutralize their main meanings when they become auxiliary. Thus, I propose to refer to these elements only as modals or modal words.

  7. First-line pharmacotherapy approaches for generalized anxiety disorder.

    Science.gov (United States)

    Davidson, Jonathan R

    2009-01-01

    Many patients with generalized anxiety disorder (GAD) do not receive adequate treatment. Several classes of drugs, including benzodiazepines, azapirones, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, antihistamines, alpha(2)delta Ca++ channel modulators, and atypical antipsychotics are consistently beneficial in patients with GAD. Cognitive therapy is also effective as a first-line treatment. When individualizing treatment, drug dose ranges and side effect profiles need to be considered, as well as the patient's comorbid conditions. Doses may need to be reduced for elderly or medically ill patients or those taking other medications. Doses may need to be increased for refractory cases. Common comorbid conditions with GAD include depression, alcohol or drug abuse, social anxiety disorder, and panic disorder. In patients with significant depression, an antidepressant is more likely to succeed than a benzodiazepine. Generalized anxiety disorder is a chronic illness that requires long-term treatment. Remission is attainable but can take several months, and stopping medication increases the risk of relapse within the first year of initiating treatment.

  8. Patient persistence with first-line antiglaucomatous monotherapy

    Directory of Open Access Journals (Sweden)

    Alfonso Arias

    2010-04-01

    .6% (P < 0.001 and 48.6% (P < 0.001, respectively.Conclusions: Latanoprost shows higher patient persistence compared with travoprost, bimatoprost, and timolol in routine clinical practice, and could lead to better control of intraocular pressure and lower associated economic costs.Keywords: first-line monotherapy, glaucoma, treatment, persistence, Spain

  9. Changing modalities

    NARCIS (Netherlands)

    Renardel de Lavalette, Gerard R.

    2004-01-01

    The dynamic modal logic DML is presented, featuring actions that change the interpretation of a propositional variable or a modality. The semantics is defined both in terms of modal structures and of labelled transition systems (Kripke models). The extension µDML with recursively defined actions aim

  10. {sup 18}F-FDG-PET/CT in staging, restaging, and treatment response assessment of male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Groheux, David, E-mail: dgroheux@yahoo.fr [Department of Nuclear Medicine, Saint-Louis Hospital, Paris (France); Doctoral School of Biology and Biotechnology, University Institute of Hematology, University of Paris VII, Paris (France); Hindié, Elif [Department of Nuclear Medicine, Haut-Lévêque Hospital, CHU Bordeaux, University Bordeaux-Segalen, Bordeaux (France); Marty, Michel [Breast Diseases Unit and Department of Medical Oncology, Saint-Louis Hospital, Paris (France); Centre for Therapeutic Innovation, Saint-Louis Hospital, Paris (France); Espié, Marc [Breast Diseases Unit and Department of Medical Oncology, Saint-Louis Hospital, Paris (France); Rubello, Domenico [Department of Nuclear Medicine, Santa Maria della Misericordia, Rovigo Hospital, Rovigo (Italy); Vercellino, Laetitia [Department of Nuclear Medicine, Saint-Louis Hospital, Paris (France); Doctoral School of Biology and Biotechnology, University Institute of Hematology, University of Paris VII, Paris (France); Bousquet, Guilhem [Breast Diseases Unit and Department of Medical Oncology, Saint-Louis Hospital, Paris (France); INSERM U728, University Institute of Hematology, University of Paris VII, Paris (France); Ohnona, Jessica; Toubert, Marie-Elisabeth [Department of Nuclear Medicine, Saint-Louis Hospital, Paris (France); Merlet, Pascal [Department of Nuclear Medicine, Saint-Louis Hospital, Paris (France); Doctoral School of Biology and Biotechnology, University Institute of Hematology, University of Paris VII, Paris (France); Misset, Jean-Louis [Breast Diseases Unit and Department of Medical Oncology, Saint-Louis Hospital, Paris (France)

    2014-10-15

    Purpose: Male breast cancer (BC) is a rare disease, with patterns different from those found in women. Most tumors are detected at more advanced stages than in women. The aim of this study was to analyze the performance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) in staging, restaging, and therapy response assessment. Methods: We performed a systematic analysis in the database of Saint-Louis Hospital to identify male patients with BC referred for PET/CT. {sup 18}F-FDG-PET/CT findings considered suspicious for malignancy were compared to biopsy results, further work-up and/or patient follow-up of at least 6 months. Performances of {sup 18}F-FDG-PET/CT were compared to that of conventional imaging (CI) using the McNemar test. The impact of PET/CT on management was evaluated. Results: During 6 consecutive years, among 12,692 {sup 18}F-FDG-PET/CT oncology studies, 30 were performed in 15 men with BC: 7 examinations for initial staging, 11 for restaging, and 12 for response assessment. Tumors profile was ER+ and one had HER2 overexpression. PET/CT sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect distant metastases were 100%, 67%, 86%, 100% and 89%, respectively. PET/CT was more informative than CI in 40% of studies (p = 0.03; 95% confidence interval: 3.26 – 40%). Findings from {sup 18}F-FDG-PET/CT led to modification in the planned treatment in 13/30 cases (43%). Conclusion: Although all the tumors were ER+, primary lesions and metastases were diagnosed with high sensitivity. {sup 18}F-FDG-PET/CT seems to be a powerful imaging method to perform staging, restaging and treatment response assessment in male patients with BC.

  11. Accuracy of whole-body 18F-FDP-PET for restaging malignant lymphoma.

    Science.gov (United States)

    Mikosch, P; Gallowitsch, H J; Zinke-Cerwenka, W; Heinisch, M; Pipam, W; Eibl, M; Kresnik, E; Unterweger, O; Linkesch, W; Lind, P

    2003-01-01

    The aim of this retrospective study was to evaluate the accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) images, which were interpreted under daily routine conditions, in patients with Hodgkin's disease (HD) or non-Hodgkin lymphoma (NHL) for restaging after chemotherapy and/or radiotherapy. For this purpose, 18F-FDG-PET results were compared with morphological imaging methods and the patients' clinical background. 121 PET images of 93 lymphoma patients (44 HD, 49 NHL) were investigated after chemotherapy/radiotherapy. For PET imaging, 160-200 MBq 18F-FDG was administered intravenously, followed by an infusion of 20 mg Furosemid in 250 mL saline. Whole-body 18F-FDG-PET images were obtained using a partial-ring PET scanner without attenuation correction. The morphological imaging consisted in computed tomography and ultrasound (CT/US) in all patients, additional MRI in some patients, and iliac crest biopsy in cases of suspicious bone marrow involvement. The standard of reference was composed of biopsy data, clinical status at the time of investigation, and follow-up of at least 12 months. The PET images were evaluated for their sensitivity, specificity and accuracy based on written reports, which were compiled from other imaging data and the clinical history of the patients. Sensitivity, specificity, and accuracy of 18F-FDG-PET was 91 %, 81 %, and 85 %; of CT/US, 88 %, 35 %, 56 %, respectively. Major sources of error in 18F-FDG-PET were due to asymmetric muscular hypermetabolism and inflammatory lesions misinterpreted as persistent viable lymphoma tissue. Furthermore, secondary malignancies other than lymphomas were another reason for misinterpretations of 18F-FDG-PET studies. 18F-FDG-PET showed a comparable sensitivity but a higher specificity and accuracy compared with CT/US. To achieve a high accuracy in 18F-FDG-PET, the nuclear medicine specialist needs imaging and clinical data as background information, which can only be

  12. Defeasible modalities

    CSIR Research Space (South Africa)

    Britz, K

    2013-01-01

    Full Text Available with a preference ordering on worlds in Kripke models. The resulting family of modal logics allow for the elegant expression of defeasible modalities. We also propose a tableau calculus which is sound and complete with respect to our preferential...

  13. Implementing Human Resource Management Successfully: A First-Line Management Challenge

    NARCIS (Netherlands)

    Bos-Nehles, Anna Christina; van Riemsdijk, Maarten; Looise, Jan C.

    2006-01-01

    In this paper we will address the success of Human Resource Management (HRM) implementation, concentrating not on the HR function but on first-line managers. First-line managers find implementing HR practices at the operational level difficult and show reluctance with their HR responsibilities.

  14. Restaging of locally advanced carcinoma of the rectum with MR imaging after preoperative radio-chemotherapy plus regional hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, K.T.; Wust, P.; Stroszczynski, C.; Felix, R. [Dept. of Radiology and Radiation Oncology, Campus Virchow-Klinikum, Charite (Germany); Rau, B.; Huenerbein, M. [Div. of Surgery and Surgical Oncology, Robert-Roessle Hospital and Tumor Inst., Humboldt Univ. Berlin (Germany); Schneider, U. [Inst. of Pathology, Campus Buch, Charite, Robert-Roessle Hospital and Tumor Inst., Humboldt Univ. Berlin (Germany)

    2002-07-01

    Background: The restaging accuracy of MR imaging in advanced primary rectal carcinoma after preoperative radiochemotherapy and regional hyperthermia was evaluated and compared with the histopathologically verified degree of tumor remission after a course of radio-chemo-thermotherapy. Patients and Methods: 35 patients with primary rectal carcinoma (uT3/uT4) underwent MRI using a surface coil 4-6 weeks after radiochemotherapy (n=35), regional hyperthermia (n=23), and before curative surgery. We defined as gold standard for the remission status the comparison of pretherapeutic endosonography with the histopathology of the resected specimen. Results: T category was correctly restaged after preoperative treatment in only 19 (54%) of 35 patients. Nine of 20 responders were overstaged and seven of 15 non-responders were understaged. Concurrently, the N category was correctly restaged in 19 (54%) of 35 patients (twelve responders and seven non-responders). Overstaging occurred in four responders and two non-responders, understaging occurred in four responders and six non-responders. Conclusions: MRI proved independent of the response status as not suitable to restage locally advanced rectal carcinoma after preoperative radiochemotherapy despite optimized imaging technique and spatial resolution. Basically, imaging the morphology of a tumor cannot clearly differentiate between vital and devitalized tissue after a treatment. Functional imaging such as PET (positron emission tomography) appears more feasible for restaging after radio-chemo-thermotherapy. (orig.) [German] Hintergrund: Die Genauigkeit der Stadienbestimmung mittels MR-Bildgebung wurde bei primaer fortgeschrittenen Rektumkarzinomen nach praeoperativer Radiochemotherapie und regionaler Hyperthermie gepueft und mit der histopathologisch ermittelten Tumorremission nach praeoperativer Behandlung verglichen. Patienten und Methode: 35 Patienten mit primaeren Rektumkarzinomen (uT3/uT4) wurden MR-tomographisch mittels

  15. First-Line First? Trends in Thiazide Prescribing for Hypertensive Seniors

    Directory of Open Access Journals (Sweden)

    Morgan Steve

    2005-01-01

    Full Text Available Background Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. Methods and Findings British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. Conclusions Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the most

  16. First-line first? Trends in thiazide prescribing for hypertensive seniors.

    Directory of Open Access Journals (Sweden)

    Steve Morgan

    2005-04-01

    Full Text Available BACKGROUND: Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. METHODS AND FINDINGS: British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. CONCLUSIONS: Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the

  17. First-line managers: scope of responsibility in a time of fiscal restraint.

    Science.gov (United States)

    Acorn, S; Crawford, M

    1996-01-01

    Fiscal restraint and government cost control have contributed to the downsizing and restructuring of Canadian health care organizations. As key players in the hospital sector, the role and responsibilities of first-line nurse managers have been significantly affected by these changes. This paper presents data from a survey of 200 first-line nurse managers in British Columbia which investigated the current scope of the first-line manager's role, the number of hierarchical levels within nursing departments, and views on managerial union membership.

  18. Comparison of EUS-guided fine needle aspiration and integrated PET-CT in restaging after treatment for locally advanced non-small cell lung cancer

    NARCIS (Netherlands)

    Stigt, Jos A.; Oostdijk, Ad H.; Timmer, Paul R.; Shahin, Ghada M.; Boers, James E.; Groen, HarryJ. M.

    2009-01-01

    Background: After induction treatment restaging of mediastinal disease in patients with stage III non-small cell lung cancer (NSCLC) may lead to selection of candidates for further surgical treatment. Nodal down-staging is the best predictive characteristic for proceeding with surgery. We report our

  19. Restaging oesophageal cancer after neoadjuvant therapy with {sup 18}F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, John M. [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Churchill Hospital, NIHR Oxford Biomedical Research Centre, Oxford (United Kingdom); Gillies, Richard S.; Maynard, Nicholas D. [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Franklin, James M.; Teoh, Eugene J.; Gleeson, Fergus V.; Bradley, Kevin M. [Churchill Hospital, Department of Nuclear Medicine, Oxford (United Kingdom); Jones, Greg E. [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Royal Berkshire Hospital, Reading (United Kingdom); Di Carlo, Sara [Churchill Hospital, Oxford OesophagoGastric Centre, Oxford (United Kingdom); Queen' s Medical Centre, Nottingham (United Kingdom); Middleton, Mark R. [Churchill Hospital, NIHR Oxford Biomedical Research Centre, Oxford (United Kingdom)

    2016-10-15

    It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk. This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by {sup 18}F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014). Three hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91 %) and PET-CT in 17 (6.07 %). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1 %). PET-CT was more sensitive than CT (p = 0.005, McNemar's test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0 %; both risk factors), medium (22.4 %; either), and low risk (3.87 %; neither) groups (p < 0.001). Decision theory supported restaging PET-CT. PET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply. (orig.)

  20. Analysis on Modals and Semi-Modals

    Institute of Scientific and Technical Information of China (English)

    陈力

    2014-01-01

    The modal is a type of auxiliary verb that is used to indicate modality. There are thirteen modal auxiliaries including some past tense forms. In this paper, the modals and semi-modals will be studied through analyzing fifteen sample sentences and referring some grammar books. At last, some suggestions for ESL or ESL teacher to teach modals will be provided.

  1. First-Line Nursing Home Managers in Sweden and their Views on Leadership and Palliative Care.

    Science.gov (United States)

    Håkanson, Cecilia; Cronfalk, Berit Seiger; Henriksen, Eva; Norberg, Astrid; Ternestedt, Britt-Marie; Sandberg, Jonas

    2014-01-01

    The aim of this study was to investigate first-line nursing home managers' views on their leadership and related to that, palliative care. Previous research reveals insufficient palliation, and a number of barriers towards implementation of palliative care in nursing homes. Among those barriers are issues related to leadership quality. First-line managers play a pivotal role, as they influence working conditions and quality of care. Nine first-line managers, from different nursing homes in Sweden participated in the study. Semi-structured interviews were conducted and analysed using qualitative descriptive content analysis. In the results, two categories were identified: embracing the role of leader and being a victim of circumstances, illuminating how the first-line managers handle expectations and challenges linked to the leadership role and responsibility for palliative care. The results reveal views corresponding to committed leaders, acting upon demands and expectations, but also to leaders appearing to have resigned from the leadership role, and who express powerlessness with little possibility to influence care. The first line managers reported their own limited knowledge about palliative care to limit their possibilities of taking full leadership responsibility for implementing palliative care principles in their nursing homes. The study stresses that for the provision of high quality palliative care in nursing homes, first-line managers need to be knowledgeable about palliative care, and they need supportive organizations with clear expectations and goals about palliative care. Future action and learning oriented research projects for the implementation of palliative care principles, in which first line managers actively participate, are suggested.

  2. Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.

    Directory of Open Access Journals (Sweden)

    Susana Monge

    Full Text Available BACKGROUND: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR defined by the 2009 update of the WHO SDRM list. METHODS: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant". RESULTS: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9 vs. 3.6% (2.9-4.3 by the WHO list] and PIs [0.8% (0.4-1.1 vs. 1.7% (1.2-2.2], while it was higher for NNRTIs [4.6% (3.8-5.3 vs. 3.7% (3.0-4.7]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02. CONCLUSIONS: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

  3. Developing a predictive risk model for first-line antiretroviral therapy failure in South Africa

    Directory of Open Access Journals (Sweden)

    Julia K Rohr

    2016-09-01

    Full Text Available Introduction: A substantial number of patients with HIV in South Africa have failed first-line antiretroviral therapy (ART. Although individual predictors of first-line ART failure have been identified, few studies in resource-limited settings have been large enough for predictive modelling. Understanding the absolute risk of first-line failure is useful for patient monitoring and for effectively targeting limited resources for second-line ART. We developed a predictive model to identify patients at the greatest risk of virologic failure on first-line ART, and to estimate the proportion of patients needing second-line ART over five years on treatment. Methods: A cohort of patients aged ≥18 years from nine South African HIV clinics on first-line ART for at least six months were included. Viral load measurements and baseline predictors were obtained from medical records. We used stepwise selection of predictors in accelerated failure-time models to predict virologic failure on first-line ART (two consecutive viral load levels >1000 copies/mL. Multiple imputations were used to assign missing baseline variables. The final model was selected using internal-external cross-validation maximizing model calibration at five years on ART, and model discrimination, measured using Harrell's C-statistic. Model covariates were used to create a predictive score for risk group of ART failure. Results: A total of 72,181 patients were included in the analysis, with an average of 21.5 months (IQR: 8.8–41.5 of follow-up time on first-line ART. The final predictive model had a Weibull distribution and the final predictors of virologic failure were men of all ages, young women, nevirapine use in first-line regimen, low baseline CD4 count, high mean corpuscular volume, low haemoglobin, history of TB and missed visits during the first six months on ART. About 24.4% of patients in the highest quintile and 9.4% of patients in the lowest quintile of risk were predicted

  4. Complete Genome Sequences of Neisseria gonorrhoeae with Coresistance to First-Line Antimicrobials

    Science.gov (United States)

    Bharat, Amrita; Martin, Irene; Demczuk, Walter; Allen, Vanessa; Haldane, David; Hoang, Linda

    2016-01-01

    Neisseria gonorrhoeae strains with coresistance to the first-line antimicrobial treatments azithromycin and ceftriaxone are an emerging public health threat. Here, we present the complete genome sequences of three strains of N. gonorrhoeae, including one susceptible strain and two strains with coresistance to ceftriaxone and azithromycin. PMID:27609929

  5. First-line treatment of chronic lymphocytic leukemia with three combined chemotherapy regimens

    Directory of Open Access Journals (Sweden)

    Matevž Škerget

    2012-12-01

    Conclusions: RFC is the first-line treatment of choice for younger fit patients without deletion 17. For older and frail patients, alternative newer chemotherapy regimens should be sought. Patients with deletion 17 should receive alemtuzumab treatment, and allogeneic bone marrow transplantation should be considered.

  6. Complete Genome Sequences of Neisseria gonorrhoeae with Coresistance to First-Line Antimicrobials

    OpenAIRE

    Bharat, Amrita; Martin, Irene; Demczuk, Walter; Allen, Vanessa; Haldane, David; Hoang, Linda; Mulvey, Michael R.

    2016-01-01

    Neisseria gonorrhoeae strains with coresistance to the first-line antimicrobial treatments azithromycin and ceftriaxone are an emerging public health threat. Here, we present the complete genome sequences of three strains of N. gonorrhoeae, including one susceptible strain and two strains with coresistance to ceftriaxone and azithromycin.

  7. Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Marthin, J K; Nielsen, K G

    2011-01-01

    as first-line tests for PCD. Healthy subjects, confirmed PCDs, consecutive referrals with PCD-like symptoms and patients with cystic fibrosis (CF) had nNO sampled during breath hold (BH-nNO), oral exhalation against resistance (OE-R-nNO) and tidal breathing (TB-nNO) aiming to expand age range into infancy...

  8. Clonidine as a First-Line Sedative Agent After Neonatal Cardiac Surgery: Retrospective Cohort Study

    NARCIS (Netherlands)

    Kleiber, N.; Wildt, S.N. de; Cortina, G.; Clifford, M.; Ducruet, T.; Tibboel, D.; Millar, J.

    2016-01-01

    OBJECTIVES: To determine the cardiovascular tolerance of clonidine used as a first-line sedative after cardiac surgery in small infants. DESIGN: Retrospective chart review. SETTING: A tertiary and quaternary referral cardiac PICU. PATIENTS: All infants younger than 2 months who received a clonidine

  9. Factors impacting treatment choice in the first-line treatment of colorectal cancer

    NARCIS (Netherlands)

    Bloem, L.T.; De Abreu Lourenco, Richard; Chin, Melvin; Ly, Brett; Haas, Marion

    2016-01-01

    Introduction To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC). Methods Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in

  10. Managerial work behavior and hierarchical level: implications for the managerial training of first-line supervisors.

    Science.gov (United States)

    Rodela, E S

    1991-04-01

    Mintzberg proposed that managers at all levels enact ten roles. There is, however, a relative importance ascribed to the various roles given the manager's location in the hierarchy. Like Mintzberg's ideas on the utility of ten roles, we found that managers at all levels, to varying degrees, need the three skills proposed by Katz. We have argued that a variety of roles and skills describe what managers do. At the same time, the predominance of one role or skill over another may be influenced by the location of the manager in the hierarchy. The question is not whether roles would be enacted at different levels or whether skills will be required, but whether one role or skill or a set of roles and skills will be predominant for the first-line supervisor. The first-line supervisor's work requires that he or she be predominantly proficient in the areas of human and technical skills in order to fulfill supervisory responsibilities. Current empirical research supports this assertion; however, the continuing study of managerial roles and skills and other variables such as functional specialty will offer other opportunities for the study of first-line supervisors. For example, will the predominance of the roles and skills that we have discussed vary if the supervisor is a line or staff manager or if the supervisor works in a production or service related organization? Organizations adapt to change to meet the expectations of those within and outside the organization with something at stake. Organizations need managers to facilitate the realization of organizational goals, so organizations need to continuously train managers, targeting appropriate roles and skills given each manager's location in the hierarchy. The preceding pages should provide resource materials to individuals and organizations interested in evaluating and designing the training and development of first-line supervisors. This roles-and-skills information can be productively utilized to assist the

  11. Shock treatment: using immersive digital realism to restage and re-examine milgram's 'obedience to authority' research.

    Science.gov (United States)

    Haslam, S Alexander; Reicher, Stephen D; Millard, Kathryn

    2015-01-01

    Attempts to revisit Milgram's 'Obedience to Authority' (OtA) paradigm present serious ethical challenges. In recent years new paradigms have been developed to circumvent these challenges but none involve using Milgram's own procedures and asking naïve participants to deliver the maximum level of shock. This was achieved in the present research by using Immersive Digital Realism (IDR) to revisit the OtA paradigm. IDR is a dramatic method that involves a director collaborating with professional actors to develop characters, the strategic withholding of contextual information, and immersion in a real-world environment. 14 actors took part in an IDR study in which they were assigned to conditions that restaged Milgrams's New Baseline ('Coronary') condition and four other variants. Post-experimental interviews also assessed participants' identification with Experimenter and Learner. Participants' behaviour closely resembled that observed in Milgram's original research. In particular, this was evidenced by (a) all being willing to administer shocks greater than 150 volts, (b) near-universal refusal to continue after being told by the Experimenter that "you have no other choice, you must continue" (Milgram's fourth prod and the one most resembling an order), and (c) a strong correlation between the maximum level of shock that participants administered and the mean maximum shock delivered in the corresponding variant in Milgram's own research. Consistent with an engaged follower account, relative identification with the Experimenter (vs. the Learner) was also a good predictor of the maximum shock that participants administered.

  12. Noninvasive nodal restaging in clinically node positive breast cancer patients after neoadjuvant systemic therapy: A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Schipper, R.J., E-mail: info@rjschipper.nl [Department of Radiology, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Moossdorff, M. [Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Beets-Tan, R.G.H. [Department of Radiology, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Smidt, M.L. [Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Lobbes, M.B.I. [Department of Radiology, Maastricht University Medical Center+, Maastricht (Netherlands)

    2015-01-15

    Objective: To provide a systematic review of studies comparing the diagnostic performance of noninvasive techniques and axillary lymph node dissection in the identification of initially node positive patients with pathological complete response of axillary lymph nodes to neoadjuvant systemic therapy. Methods: PubMed and Embase databases were searched until May 21st, 2014. First, duplicate studies were eliminated. Next, study abstracts were read by two readers to assess eligibility. Studies were selected based on predefined inclusion criteria. Of these, data extraction was performed by two readers independently. Results: Of the 987 abstracts that were considered for inclusion, four were eligible for final analysis, which included a total of 572 patients. The diagnostic performance of clinical examination, axillary ultrasound, breast MRI, whole body {sup 18}F-FDG PET-CT, and a prediction model to identify patients with pathological complete response were investigated. Studies were often limited by small sample size. Furthermore, systemic therapy regimens and definitions of clinical and pathological complete response were variable, refraining further pooling of data. The reported positive predictive value of different techniques to identify patients with axillary pathological complete response after neoadjuvant systemic therapy varied between 40% and 100%. Conclusion: At present, there is no accurate noninvasive restaging technique able to identify patients with complete axillary response after neoadjuvant systemic therapy.

  13. Modal Indicators for Operational Modal Identification

    DEFF Research Database (Denmark)

    Zhang, L.; Brincker, Rune; Andersen, P.

    2001-01-01

    Modal validation is of paramount importance for all two-stage time domain modal identification algorithms. However, due to a higher noise/signal ratio in operational/ambient modal analysis, being able to determine the right model order and to distinguish between structural modes and computational...... modes become more significant than in traditional modal analysis. The two major modal indicators, i.e. Modal Confidence Factor (MCF) and Modal Amplitude Coherence (MAmC) are extended to two-stage time domain modal identification algorithms, together with a newly developed indicator, named as Modal...... Participation Indicator (MPI). The application of the three indicators is illustrated on different cases of operational/ambient modal identification. Three major time domain modal identification algorithms are used the Polyreference Complex Exponential (PRCE), Extended Ibrahim Time Domain (EITD), Eigensystem...

  14. Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Eboua, François T; Malateste, Karen

    2015-01-01

    BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric Ie......DEA clinical centres in five West-African countries. We estimated the incidence of switch (at least one a drug class change) within 24 months of ART and associated factors were identified in a multinomial logistic regression. Among children with clinical-immunological failure, we estimated the 24-month...... probability of switching to a second-line and associated factors, using competing risks. Children who switched to second-line ART following the withdrawal of nelfinavir in 2007 were excluded. RESULTS: Overall, 2820 children initiated ART at a median age of 5 years; 144 (5%) were on nelfinavir. At 24-month...

  15. Serum tumour marker CA 125 in monitoring of ovarian cancer during first-line chemotherapy

    DEFF Research Database (Denmark)

    Tuxen, M K; Sölétormos, G; Dombernowsky, P

    2001-01-01

    of this study was to assess the ability of CA 125 to monitor patients with ovarian cancer during postoperative chemotherapy. 255 patients with stage IC-IV ovarian cancer were allocated to the tumour marker monitoring study. The evaluation of CA 125 information was based on the analytical imprecision, the normal...... for identifying progression and non-progression during first-line chemotherapy was 91.9%. The median lead time for true positive results was 41 days. Using the new elaborated criterion the efficiency of CA 125 for identifying progression and non-progression during first-line chemotherapy was 90.5%. The median...... lead time for true positive results was 35 days. CA 125 gave reliable prediction of progressive disease during postoperative chemotherapy. The results indicate a high applicability of the presented progression criteria during CA 125 monitoring of patients with changing activity of ovarian cancer....

  16. Hormonal therapy for acne: why not as first line therapy? facts and controversies.

    Science.gov (United States)

    Katsambas, Andreas D; Dessinioti, Clio

    2010-01-01

    Standard systemic therapeutic agents used in acne include oral antimicrobials, isotretinoin, and hormonal agents. Appropriate patient selection is the key to decide when to use hormonal agents as first-line therapy as well as to achieve optimal results. Indications of hormonal therapy in acne in girls and women include proven ovarian or adrenal hyperandrogenism, recalcitrant acne, acne not responding to repeated courses of oral isotretinoin, acne tarda, polycystic ovary syndrome, or the presence of clinical signs of hyperandrogenism such as androgenic alopecia or the presence of the seborrhea, acne, hirsutism, alopecia syndrome. We describe the hormonal agents currently available for acne treatment, discuss their indications and contraindications, and address the question of whether they may be used as a first-line therapy in acne.

  17. Bevacizumab-based therapies in the first-line treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Strickler, John H; Hurwitz, Herbert I

    2012-01-01

    Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting.

  18. Exploiting Tumor Activated Testes Proteins To Enhance Efficacy of First Line Chemotherapeutics in NSCLC

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0428 TITLE: Exploiting Tumor -Activated Testes Proteins To Enhance Efficacy of First-Line Chemotherapeutics in NSCLC...Annual 3. DATES COVERED 30 Sep 2015 – 29 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Exploiting Tumor -Activated Testes Proteins To Enhance...hypothesize that CTAs promote repair of these DSB in NSCLC and are essential for tumor cell survival. To evaluate this hypothesis, we are investigating the

  19. First-line managers' experiences of alternative modes of funding in elderly care in Sweden.

    Science.gov (United States)

    Antonsson, Helen; Korjonen, Susanne Eriksson; Rosengren, Kristina

    2012-09-01

    The aim of this study was to describe first-line managers' experiences of alternative modes of funding elderly care in two communities in western Sweden. A growing elderly population demands alternative modes of funding elderly care for better outcomes for patients and better efficiency as it is publicly funded through taxation. The study comprised a total of eight semi-structured interviews with first-line managers working within elderly care. The interviews were analysed using manifest qualitative content analysis. Respect for the individuals was a main concern in the study. One category, quality improvement, and four subcategories freedom of choice, organisational structure, quality awareness and market forces effects were identified to describe first-line managers' experiences of the operation of elderly care. Quality improvement was an important factor to deal with when elderly care was operated in different organisational perspectives, either private or public. The first-line manager is a key person for developing a learning organisation that encourages both staff, clients and their relatives to improve the organisation. Moreover, person-centred care strengthens the client's role in the organisation, which is in line with the government's goal for the quality improvement of elderly care. However, further research is needed on how quality improvement could be developed when different caregivers operate in the same market in order to improve care from the elderly perspective. This study highlights alternative modes of funding elderly care. The economical perspectives should not dominate without taking care of quality improvement when the operation of elderly care is planned and implemented. Strategies such as a learning organisational structure built on person-centred care could create quality improvement in elderly care. © 2012 Blackwell Publishing Ltd.

  20. Is zidovudine first-line therapy virologically comparable to tenofovir in resource-limited settings?

    Science.gov (United States)

    Labhardt, Niklaus D; Bader, Joëlle; Lejone, Thabo Ismael; Ringera, Isaac; Puga, Daniel; Glass, Tracy R; Klimkait, Thomas

    2015-07-01

    To compare virologic success between adult patients on tenofovir (TDF) and zidovudine (AZT)-containing first-line antiretroviral (ART) regimens in 10 rural clinics in Lesotho, Southern Africa. Multicentre cross-sectional study, patients ≥16 years, on first-line ART ≥6 months, receiving AZT/lamivudine (3TC) or TDF/3TC combined with efavirenz (EFV) or nevirapine (NVP). Patient characteristics and clinical/therapeutic history were collected on the day of blood draw for viral load (VL). Analysis was stratified for non-nucleoside reverse transcriptase inhibitor (EFV or NVP). A logistic regression model weighted for patients' baseline characteristics was used to assess the likelihood of virologic success (<80 copies/ml) in patients with TDF- as compared to AZT-backbones. In total 1539 patients were included in the analysis. Most were clinically and immunologically stable (clinical failure: 2.7% (AZT) and 2.8% (TDF); immunological failure: 4.6% (AZT) and 4.8% (TDF)). In EFV-based regimens (n = 1162), TDF was significantly associated with higher rates of virologic suppression than AZT (93.8% vs. 88.1%; weighted odds ratio: 2.15 (95% CI: 1.29-3.58; P = 0.003)). In NVP-based regimens, a similar trend was observed, but not significant (89.4% vs. 86.7%; 1.99 (0.83-4.75, P = 0.121)). These findings support the WHO recommendation to use TDF/3TC/EFV as first-line regimen. They do, however, not support the recommendation that patients who are clinically stable on AZT should continue on this first-line regimen. © 2015 John Wiley & Sons Ltd.

  1. Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer

    OpenAIRE

    Feliu Batlle, Jaime; Safont, María José; Salud, Antonieta T.; Losa, Ferrán C.; García-Girón, Carlos; Bosch, Carles J A; Escudero, Pilar; López Manzanera, Rafael; Madroñal, C; Bolaños, Margarita; Gil, Mireia; Llombart, Antonio C.; Castro-Carpeño, J; González Barón, Manuel

    2010-01-01

    BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mgm 2 (or 950 mgm 2 for patients with a creatinine clearance of 30–50ml min 1) twice daily on days 1–14 and bevacizumab (7.5 m...

  2. Factors Impacting Treatment Choice in the First-Line Treatment of Colorectal Cancer

    OpenAIRE

    Bloem, L.T.; De Abreu Lourenco, Richard; Chin, Melvin; Ly, Brett; Haas, Marion

    2016-01-01

    Introduction To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC). Methods Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital?s database MOSAIQ?. The electronic medical record of each patient was manually reviewed to extract...

  3. First-line nurse leaders' health-care change management initiatives.

    Science.gov (United States)

    Macphee, Maura; Suryaprakash, Nitya

    2012-03-01

    To examine nurse leaders' change management projects within British Columbia, Canada. British Columbia Nursing Leadership Institute 2007-10 attendees worked on year-long change management initiatives/projects of importance to their respective health-care institutions. Most leaders were in first-line positions with Change management, a universal competency, must be included in leadership development programmes. © 2011 Blackwell Publishing Ltd.

  4. Benzodiazepines should still be first-line treatment for alcohol withdrawal

    DEFF Research Database (Denmark)

    Askgaard, Gro; Pottegård, Anton; Fink-Jensen, Anders

    2017-01-01

    In this review, we summarize the evidence for benzodiazepines and barbiturates as alcohol withdrawal treatment and outline a treatment guideline. A number of randomized controlled trials (RCTs) indicate that benzodiazepine treatment decreases alcohol withdrawal seizures and is safe....... For barbiturates, only a few RCTs have been undertaken, and barbiturates were not found to be superior to benzodiazepines. Consequently, we suggest that benzodiazepines should still be first-line treatment for alcohol withdrawal....

  5. Resilience and work-life balance in first-line nurse manager.

    Science.gov (United States)

    Kim, Miyoung; Windsor, Carol

    2015-03-01

    The aim of this study was to explore how first-line nurse managers constructed the meaning of resilience and its relationship to work-life balance for nurses in Korea. Participants were 20 first-line nurse managers working in six university hospitals. Data were collected through in-depth interviews from December 2011 to August 2012, and analyzed using Strauss and Corbin's grounded theory method. Analysis revealed that participants perceived work-life balance and resilience to be shaped by dynamic, reflective processes. The features consisting resilience included "positive thinking", "flexibility", "assuming responsibility", and "separating work and life". This perception of resilience has the potential to facilitate a shift in focus from negative to positive experiences, from rigidity to flexibility, from task-centered to person-centered thinking, and from the organization to life. Recognizing the importance of work-life balance in producing and sustaining resilience in first-line nurse managers could increase retention in the Korean nursing workforce. Copyright © 2015. Published by Elsevier B.V.

  6. Outcomes in achalasia from a surgical unit where pneumatic dilatation is first-line therapy.

    Science.gov (United States)

    Howard, J M; Mongan, A-M; Manning, B J; Byrne, P; Lawler, P; Ravi, N; Reynolds, J V

    2010-08-01

    The management of achalasia remains controversial, with little consensus on the optimal patient treatment pathway. In our own esophageal unit, we offer pneumatic dilatation as the initial therapy in most patients as first-line therapy. In this study, we aimed to examine the safety and efficacy of our own approach to the management of patients with a diagnosis of achalasia, examining symptomatic outcomes, patient satisfaction, and need for further intervention, as well as examining patient factors associated with treatment failure. Sixty-seven consecutive patients underwent pneumatic dilatation as first-line therapy (53% male, mean age 46 years). All attended regular outpatient follow-up (mean 37, range 3-132 months). Twenty-five percent of patients required a second intervention because of symptom recurrence, at a median period of 4.5 months. Symptomatic outcomes were excellent or good in 80%. Significant predictors of treatment failure and poor symptom score included a younger age at the time of diagnosis and increased esophageal diameter on barium swallow. This study suggests that pneumatic dilatation is a safe and effective approach as first-line therapy in patients with newly diagnosed achalasia.

  7. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib

    Directory of Open Access Journals (Sweden)

    Rafiyath Shamudheen

    2010-11-01

    Full Text Available Abstract Imatinib, a tyrosine kinase inhibitor (TKI of BCR-ABL, was the standard first-line therapy for chronic myeloid leukemia (CML for almost 10 years. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have each shown superior efficacy compared with imatinib for first-line treatment of chronic-phase CML in randomized phase 3 trials. With 14 months follow-up time, available data suggest no obvious differences in efficacy between dasatinib and nilotinib. Compared with imatinib, dasatinib is associated with higher rates of pleural effusion and thrombocytopenia, but lower rates of edema, gastrointestinal AEs, musculoskeletal AEs, and rash. Nilotinib is associated with higher rates of dermatologic toxicity, headache, and biochemical abnormalities associated with hepatic and pancreatic toxicity compared with imatinib, but lower rates of edema, gastrointestinal AEs, muscle spasm, and neutropenia. Several studies have shown that poor adherence to imatinib detrimentally affects responses and should be considered in patients with a suboptimal response. The different dosing requirements of dasatinib (once daily with or without food and nilotinib (twice daily with fasting may be an additional factor in selecting frontline agents. This review compares and contrasts the three FDA approved first line TKI agents.

  8. Capecitabine Maintenance Therapy after First-Line Chemotherapy in Patients with Metastatic Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Jing Li; Ming Lu; Xi-cheng Wang; Lin Shen

    2010-01-01

    Objective:To evaluate the efficacy and toxicity of capecitabine maintenance therapy in metastatic colorectal cancer(mCRC)patients.Methods:From June 2001 to November 2006,after they had achieved clinical response from first-line chemotherapy,patients with mCRC in our hospital received two different treatment strategies.Thirty-three patients non-maintenance group did not receive any further chemotherapy.Results:Patients in maintenance group and non-maintenance group both received FOLFOX,FOLFIRI and XELOX as first-line therapy.The median chemotherapy cycles the two groups received were the same(6 vs 6).The response rates of first-line chemotherapy were 33.3% in maintenance group and 32.7% in non-maintenance group.Patients in maintenance group received 3-9 cycles of capecitabine therapy(median cycle 4).29/33(87.9%)patients in maintenance group and 47/52(90.4%)in non-maintenance group received following second-line chemotherapy,and no patients underwent targeted therapy.The median survival time and TTP were 40.4 months(95%CI:24.2-56.6)and 9.0 months(95%CI:6.7-11.3)in maintenance group,as compared with 21.5 months(95%CI:14.9-28.0,P=0.015)and 6.5 months(95%CI:4.4-8.5,P=0.007)in non-maintenance group.No severe adverse event was observed in the capecitabine maintenance group.Conclusion:mCRC patients could benefit from capecitabine maintenance therapy by prolonging survival time and TTP.

  9. Primary HIV drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing.

    Science.gov (United States)

    Oette, Mark; Kaiser, Rolf; Däumer, Martin; Petch, Ruth; Fätkenheuer, Gerd; Carls, Horst; Rockstroh, Jürgen Kurt; Schmalöer, Dirk; Stechel, Jürgen; Feldt, Torsten; Pfister, Herbert; Häussinger, Dieter

    2006-04-15

    Primary HIV drug resistance has been associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART) in several trials. The aim of the study was to assess the efficacy of first-line HAART guided by resistance testing. In a prospective multicenter study in the state of Nordrhein-Westfalen, Germany, chronically HIV-infected patients underwent genotypic resistance testing and were monitored for 48 weeks after initiation of HAART. Primary drug resistance was found in 30 of 269 patients entering the study between January 2001 and December 2003 [11.2%; 95% confidence interval, 7.4-14.9]. In intent-to-treat analysis, the proportion of patients with viral load below 50 copies/mL after 24 and 48 weeks was 70.0% and 66.7%, respectively, in patients with resistance and 74.1% and 73.6%, respectively, in patients without (P = 0.66 and 0.51). In on-treatment analysis, the proportions were 80.8% and 83.3%, respectively, in patients with resistance and 81.9% and 85.0%, respectively, in patients without (P= 0.79 and 0.77). These results were also valid considering a detection limit of 400 copies/mL. The prevalence of primary drug resistance was 11.2% in chronically HIV-infected patients. HAART guided by resistance testing had similar efficacy in patients with primary drug resistance as compared with patients with wild-type virus. Based on these facts, resistance-adapted first-line HAART is suggested as routine practice.

  10. Outcomes of first-line treatment for chronic lymphocytic leukemia with 17p deletion.

    Science.gov (United States)

    Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Ferrajoli, Alessandra; Burger, Jan; Faderl, Stefan; Tambaro, Francesco Paolo; Jain, Nitin; Wierda, William G

    2014-08-01

    Although uncommon in treatment-naive patients with chronic lymphocytic leukemia, deletion 17p is a high-risk disease characteristic. We analyzed and reported outcomes for 63 patients with deletion 17p chronic lymphocytic leukemia who received first-line therapy at our institution; at time of first treatment, 81% had unmutated immunoglobulin heavy chain variable gene and 58% had complex karyotype. Forty-nine patients (76%) received first-line fludarabine, cyclophosphamide, rituximab-based therapy, 6 (11%) received rituximab-based and 8 (13%) received lenalidomide-based treatment. Overall, the complete plus nodular partial remission rate was 33%; on multivariable model, higher complete plus nodular partial remission rate was observed in patients with less than 50% cells positive for deletion 17p, and a higher probability of achieving at least a partial remission was observed with fludarabine, cyclophosphamide, rituximab-based treatment. After a median follow up of 33 months (range 1-89 months), the estimated median progression-free survival was 14 months (95% confidence interval 10-18) and estimated median overall survival was 63 months (95% confidence interval 43-83). In multivariable analysis, factors independently associated with longer progression-free survival were response to treatment and absence of complex karyotype. Achievement of complete plus nodular partial remission rate and mutated immunoglobulin heavy chain variable gene were independently associated with longer overall survival in multivariable model. Complex karyotype was associated with increased risk for Richter's transformation. New first-line strategies and agents must aim at both improving response and maintaining remission in patients with deletion 17p, particularly in the presence of complex karyotype.

  11. Factors Impacting Treatment Choice in the First-Line Treatment of Colorectal Cancer.

    Science.gov (United States)

    Bloem, Lourens T; De Abreu Lourenço, Richard; Chin, Melvin; Ly, Brett; Haas, Marion

    2016-01-01

    To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC). Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital's database MOSAIQ(®). The electronic medical record of each patient was manually reviewed to extract factors potentially affecting treatment choice. Logistic regression was used to assess which patient and/or treatment factors could explain the choice between 5-FU or capecitabine. Where it was available in the medical correspondence, the explicit reason for the choice made was extracted. 170 CRC patients were included; 119 on 5-FU, and 51 on capecitabine. The odds of receiving capecitabine as a first-line treatment were positively associated with giving patients a choice in the decision (OR = 17.51, 95% CI: 5.37-57.08). Qualitative data suggest treatment choices were motivated by convenience (oral administration) and tolerability. Time from diagnosis to treatment commencement (OR = 1.02 per month, 95% CI 1.00-1.04) was also found to be positively associated with the choice of capecitabine. The odds of being treated with capecitabine were lower for patients who lived further from the treating hospital (OR = 0.22, 95% CI 0.05-0.94). This study suggests that patient choice, favoring oral capecitabine over i.v. 5-FU, was a key factor influencing first-line treatment for CRC in this cohort. To respect their autonomy, patients should be involved in the clinical decision making process.

  12. Autologous stem cell transplantation as first line treatment after incomplete excision of pancreatoblastoma.

    Science.gov (United States)

    Meneses, Clarice Franco; Osório, Carolina Dame; de Castro Junior, Claudio Galvão; Brunetto, Algemir Lunardi

    2013-01-01

    Pancreatoblastoma is a rare tumor and surgery with complete resection is the main treatment approach. Prognosis for patients with residual disease after surgery is usually dismal. A 14-year-old girl with pancreatoblastoma in the pancreatic body and tail was submitted to preoperative chemotherapy. She underwent surgery and the tumor was resected with microscopic margins. Postoperative chemotherapy was followed by high dose chemotherapy and autologous hematopoietic stem cell transplantation. After four years she remains very well with no evidence of disease. This is the first case reported of pancreatoblastoma that was treated with autologous hematopoietic stem cell transplantation as first line treatment without radiotherapy at the site of the microscopic disease.

  13. First-line treatment with cephalosporins in spontaneous bacterial peritonitis provides poor antibiotic coverage

    DEFF Research Database (Denmark)

    Novovic, Srdan; Semb, Synne; Olsen, Henrik

    2012-01-01

    Abstract Objective. Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial...... resistance in Denmark. Material and Methods. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study. Results. One...

  14. Vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice.The standard chemotherapy of pancreatic cancer has been gemcitabine,but the response rate is low.Therefore,it is in urgent need to explore an effective clinical therapy for this cancer.This paper,a case report,is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer.Methods A 52-year-old female pati...

  15. Can Propranolol be used as the first line treatment in infantile hemangioma?

    Directory of Open Access Journals (Sweden)

    Yasemin Altuner Torun

    2011-03-01

    Full Text Available Hemangiomas are the most common tumors of infancy. Most of them require no treatment, but treatment is needed if dramatic aesthetic, and/or functional impairment as visual or airway obstruction or ulceration arises. We reported a 6-month-old infant presented with a 6-week history of a rapidly growing cutaneus hemangioma on the right eyelid and caused visual impairment. The patient was successfully treated with the use of oral propranolol therapy. We suggest that propranolol can be considered as a first line treatment in a patient with infantil hemangioma.

  16. Interventions to improve adherence to first-line antibiotics in respiratory tract infections

    DEFF Research Database (Denmark)

    Llor, Carl; Monedero, María José; García, Guillermo

    2015-01-01

    Background: Many interventions aimed at improving the quality of antibiotic prescribing have been investigated, but more knowledge is needed regarding the impact of different intensity interventions. Objectives: To compare the effect of two interventions, a basic intervention (BI) and intensive....... In the group of GPs following the BI, first-line antibiotics accounted for 23.8% of antibiotics before the intervention and 29.4% after (increase 5.6%, 95% confidence interval (CI): 1.2-10%), while in the group of GPs following the II these figures were 26.2% and 48.6% (increase 22.4%, 95% CI: 18...

  17. Experimental modal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ibsen, Lars Bo; Liingaard, M.

    2006-12-15

    This technical report concerns the basic theory and principles for experimental modal analysis. The sections within the report are: Output-only modal analysis software, general digital analysis, basics of structural dynamics and modal analysis and system identification. (au)

  18. First-line treatment of chronic lymphocytic leukemia: role of alemtuzumab

    Directory of Open Access Journals (Sweden)

    Carmen Diana Schweighofer

    2010-03-01

    Full Text Available Carmen Diana Schweighofer1, Clemens-Martin Wendtner21Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA; 2Department of Internal Medicine I, University of Cologne, Cologne, GermanyAbstract: The CD52-targeting antibody alemtuzumab is established in clinical practice with convincing activity in relapsed and refractory chronic lymphocytic leukemia (CLL, particularly in patients with high-risk features and adverse prognosis. In the CAM307 study alemtuzumab was tested and finally approved as a first-line single agent, even though the hurdle with chlorambucil as the contender was not set very high. Within clinical trials, the drug demonstrated an excellent ability to eliminate minimal residual disease in blood and bone marrow, which has been correlated with a corresponding survival advantage in patients. However, in the maintenance setting, infectious complications due to severe T cell suppression have been highlighted and do not allow clinicans to use alemtuzumab outside of clinical trials. This review discusses potential therapeutic niches and future applications of alemtuzumab with a focus on CLL front-line treatment.Keywords: CLL, alemtuzumab, Campath, front-line, first-line treatment

  19. Efficacy and Safety of Topiramate as the First - Line Drug in the Treatment of Infantile Spasms

    Directory of Open Access Journals (Sweden)

    Razieh Fallah

    2011-05-01

    Full Text Available AbstractObjectiveInfantile Spasms (IS is one of the catastrophic epileptic syndromes of infancy.The purpose of this study was to evaluate clinical efficacy and safety oftopiramate (TPM as the first -line drug in the treatment of infantile spasms.Materials and MethodsIn a quasi- experimental study, efficacy and safety of TPM in rteatment of fortychildren with IS who were referred to pediatric neurology clinic of ShahidSadoughi University of Medical Sciences in Yazd, Iran, from September 2008to 2010 was evaluated.ResultsTwenty two girls (55% and 18 boys (45% with a mean age of 9.2 ± 3.9 months(range= 3-20 months were evaluated. Ninety percent of the patients hadsymptomatic IS. At the end of three months of TPM treatment, 40% of thepatients became seizure free, 27.5% had more than 50% reduction in seizurefrequency, 27.5% had no notable change in seizure frequency and 5% had anincreased frequency of seizures.Transient and mild side effects, which were seen in 32.5% of the patients,included drowsiness in 15%, hypotonia and hyperthermia (each one in 7.5%and anorexia and weight loss in 2.5%. All side effects disappeared in two orthree weeks of treatment.ConclusionTopiramate is an effective and safe drug in the treatment of IS and could beconsidered as the first line of treatment.

  20. Efficacy and Safety of Topiramate as the First - Line Drug in the Treatment of Infantile Spasms

    Directory of Open Access Journals (Sweden)

    Razieh FALLAH

    2011-05-01

    Full Text Available ObjectiveInfantile Spasms (IS is one of the catastrophic epileptic syndromes of infancy.The purpose of this study was to evaluate clinical efficacy and safety oftopiramate (TPM as the first -line drug in the treatment of infantile spasms.Materials and MethodsIn a quasi- experimental study, efficacy and safety of TPM in rteatment of fortychildren with IS who were referred to pediatric neurology clinic of ShahidSadoughi University of Medical Sciences in Yazd, Iran, from September 2008to 2010 was evaluated.ResultsTwenty two girls (55% and 18 boys (45% with a mean age of 9.2 ± 3.9 months(range= 3-20 months were evaluated. Ninety percent of the patients hadsymptomatic IS. At the end of three months of TPM treatment, 40% of thepatients became seizure free, 27.5% had more than 50% reduction in seizurefrequency, 27.5% had no notable change in seizure frequency and 5% had anincreased frequency of seizures.Transient and mild side effects, which were seen in 32.5% of the patients,included drowsiness in 15%, hypotonia and hyperthermia (each one in 7.5%and anorexia and weight loss in 2.5%. All side effects disappeared in two orthree weeks of treatment.ConclusionTopiramate is an effective and safe drug in the treatment of IS and could beconsidered as the first line of treatment.Keywords: Infantile spasms; Topiramate; Epilepsy.    

  1. Role of cetuximab in first-line treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Sotelo, Miguel Jhonatan; García-Paredes, Beatriz; Aguado, Carlos; Sastre, Javier; Díaz-Rubio, Eduardo

    2014-04-21

    The treatment of metastatic colorectal cancer (mCRC) has evolved considerably in the last decade, currently allowing most mCRC patients to live more than two years. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor play an important role in the current treatment of these patients. However, only antibodies directed against EGFR have a predictive marker of response, which is the mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS). Cetuximab has been shown to be effective in patients with KRAS wild-type mCRC. The CRYSTAL study showed that adding cetuximab to FOLFIRI (regimen of irinotecan, infusional fluorouracil and leucovorin) significantly improved results in the first-line treatment of KRAS wild-type mCRC. However, results that evaluate the efficacy of cetuximab in combination with oxaliplatin-based chemotherapy in this setting are contradictory. On the other hand, recent advances in the management of colorectal liver metastases have improved survival in these patients. Adding cetuximab to standard chemotherapy increases the response rate in patients with wild-type KRAS and can thus increase the resectability rate of liver metastases in this group of patients. In this paper we review the different studies assessing the efficacy of cetuximab in the first-line treatment of mCRC.

  2. Treatment patterns in major depressive disorder after an inadequate response to first-line antidepressant treatment

    Directory of Open Access Journals (Sweden)

    Garcia-Toro Mauro

    2012-09-01

    Full Text Available Abstract Background The aim of the study was to determine the most common pharmacological strategies used in the management of major depressive disorder (MDD after an inadequate response to first-line antidepressant treatment in clinical practice. Methods Multicenter, non-interventional study in adult outpatients with a DSM-IV-TR diagnosis of MDD and inadequate response to first-line antidepressant medication. Multiple logistic regression analyses were performed to identify independent factors associated with the adoption of a specific second-line strategy. Results A total of 273 patients were analyzed (mean age: 46.8 years, 67.8% female. Baseline mean Montgomery-Asberg Depression Rating Scale total score was 32.1 (95%CI 31.2-32.9. The most common strategies were: switching antidepressant medication (39.6%, augmentation (18.8%, and combination therapy (17.9%. Atypical antipsychotic drugs were the most commonly used agent for augmenting antidepressant effect. The presence of psychotic symptoms and the number of previous major depressive episodes were associated with the adoption of augmenting strategy (OR = 3.2 and 1.2, respectively. Conclusion The switch to another antidepressant agent was the most common second-line therapeutic approach. Psychiatrists chose augmentation based on a worse patients’ clinical profile (number of previous episodes and presence of psychotic symptoms.

  3. Complete and sustained response of adult medulloblastoma to first-line sonic hedgehog inhibition with vismodegib.

    Science.gov (United States)

    Lou, Emil; Schomaker, Matthew; Wilson, Jon D; Ahrens, Mary; Dolan, Michelle; Nelson, Andrew C

    2016-08-12

    Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy. In this report, we describe a sustained response of an unresectable multifocal form of adult medulloblastoma to vismodegib. Molecular analysis in this case revealed mutations in TP53 and a cytogenetic abnormality, i17q, that is prevalent and most often associated with subgroup 4 rather than the SHH-activated form of medulloblastoma. Our findings indicate that vismodegib may also block alternate, non-canonical forms of downstream SHH pathway activation. These findings provide strong impetus for further investigation of vismodegib in clinical trials in the first-line setting for pediatric and adult forms of medulloblastoma.

  4. Re-Staging the 1934 Abbey Theatre Production of Yeats’s The King of the Great Clock Tower: An Evaluation and Critique

    Directory of Open Access Journals (Sweden)

    Richard Allen Cave

    2013-03-01

    Full Text Available This essay investigates and critiques an attempt from the surviving evidence to re-stage the first performance of Yeats’s The King of the Great Clock Tower at the Abbey Theatre in 1934. This dance-drama was the last of four collaborations between the playwright and the dancer-choreographer, Ninette de Valois, during the period when she established for him a School of Ballet at the Abbey in Dublin. A wealth of evidence survives from which a performance text (as distinct from the printed text may be inferred. The limitations to be found in various kinds of extant data concerning performance (music scores, set designs, photographs, revisions to play scripts, reviews, correspondence, reminiscence are discussed in the light of the writer’s experience of bringing such a re-staging into production. The dangers of overly hypothesising or historicising are examined and devices for negotiating gaps in the evidence while being wholly transparent in one’s efforts are discussed. Finally the essay explores the many and diverse levels of collaboration on which a successful staging of one of Yeats’s dancedramas depends. In the course of that discussion the meaning of the word, collaboration, is interrogated and to some degree re-defined.

  5. Major complications of bariatric surgery: endoscopy as first-line treatment.

    Science.gov (United States)

    Eisendrath, Pierre; Deviere, Jacques

    2015-12-01

    Leaks are the most frequent early postoperative complication in the two most popular bariatric procedures, Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy. Multimodal therapy based on self-expandable stent insertion 'to cover' the defect is the most widely documented technique to date with a reported success rate >80%. Additional experimental techniques 'to close' the defect or 'to drain' the paradigestive cavity have been reported with encouraging results. The role of endoscopy in early postoperative bleeding is limited to management of bleeds arising from fresh sutures and the diagnosis of chronic sources of bleeding such as marginal ulcer after RYGB. Post-RYGB stricture is a more delayed complication than leaks and the role of endoscopic dilation as a first-line treatment in this indication is well documented. Ring and band placement are outdated procedures for obesity treatment, but might still be an indication for endoscopic removal, a technique which does not compromise further surgery, if needed.

  6. Rapid first-line discrimination of methicillin resistant Staphylococcus aureus strains using MALDI-TOF MS

    DEFF Research Database (Denmark)

    Østergaard, Claus; Grønvall Kjær Hansen, Sanne; Møller, Jens K

    2015-01-01

    Fast and reliable discrimination of methicillin-resistant Staphylococcus aureus (MRSA) isolates is essential in identifying an outbreak. Molecular typing methods, such as S. aureus protein A (spa) typing, multi locus sequence typing (MLST) and pulse field gel electrophoresis (PFGE) are generally...... used for this purpose. These methods are all relatively time-consuming and not performed routinely in all laboratories. The aim of this study is to examine whether MALDI-TOF MS can be used as a fast, simple and easily implemented method for first-line discrimination of MRSA isolates. Mass spectra from...... 600 clinical MRSA isolates were included in the study, representing 89 spa types, associated with 16 different known clonal complexes. All spectra were obtained directly from colony material obtained from overnight cultures without prior protein extraction. We identified 43 useful discriminatory m/z...

  7. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

    DEFF Research Database (Denmark)

    Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S;

    2014-01-01

    OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

  8. Voriconazole as a first-line treatment against potentially pathogenic Acanthamoeba strains from Peru.

    Science.gov (United States)

    Cabello-Vílchez, Alfonso Martín; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Reyes-Batlle, María; Sifaoui, Ines; Valladares, Basilio; Piñero, José E; Lorenzo-Morales, Jacob

    2014-02-01

    Pathogenic strains of Acanthamoeba genus are the causative agents of fatal granulomatous amoebic encephalitis and a serious sight-threatening infection of the eye known as Acanthamoeba keratitis. In a previous study, Acanthamoeba strains were isolated from nasal swabs collected from healthy individuals in Peru. In the present study, the pathogenic potential of the isolated strains was established based on temperature and osmotolerance assays as well as the secretion rate of extracellular proteases. Based on these experiments, four strains that showed the highest pathogenic potential were selected for sensitivity assays against two molecules (voriconazole and chlorhexidine) which are currently used for the treatment of Acanthamoeba infections. After performing sensitivity and activity assays, it was found that both drugs were active against the tested strains. However, voriconazole showed higher activity against the studied strains compared to chlorhexidine. Therefore, voriconazole should be established as a first-line treatment against Acanthamoeba infections at least in the studied region of Peru.

  9. Refractory autoimmune disease: an overview of when first-line therapy is not enough.

    Science.gov (United States)

    Neunert, Cindy; Farah, Roula; Yacobovich, Joanne; Neufeld, Ellis

    2016-04-01

    A recent Intercontinental Cooperative ITP Study Group (ICIS) meeting in September 2015 focused on immunomodulation across the spectrum of autoimmune conditions. It became clear to the attendees that in this wide range of conditions, there is a subset of patients that remain highly refractory to first line therapy. Therapeutic approaches to these patients vary greatly and while many different immunomodulatory agents have been investigated, few have seen universal success. We outline here the landscape of immunomodulation therapy for refractory patients across a variety of autoimmune conditions in order to highlight the variety of agents that have been studied, the lack of overall consensus about management, and the need for ongoing research in this area.

  10. [Failure of first-line antiretroviral therapy in HIV-infected children in Ouagadougou, Burkina Faso].

    Science.gov (United States)

    Kouéta, F; Yé, D; Zoungrana, A; Sacko, A; Ouédraogo-Traoré, R; Kafando, E; Ouédraogo, S

    2010-12-01

    Approximately one-fourth of the estimated 10,000 HIV-infected children in Burkina Faso are undergoing antiretroviral (ARV) therapy. At the Charles de Gaulle Pediatric Hospital Center in Ouagadougou, Burkina Faso, Support for ARV therapy began in July 2003 and a total of 250 children were undergoing treatment in late 2007. The purpose of this retrospective case-control study conducted over a period of 54 months from July 2003 to December 2007 was to investigate cases involving failure of first-line ARV therapy in particular with regard to cause. All patients (n = 32) showing poor virological, immunological, and/or clinical response to ARV therapy were considered as failures and thus included in the case group. The control group (n = 160) consisted of patients with good responses to treatment. Cases and controls were compared using the Chi-square test and odds ratio (OR) technique with a confidence interval at 95%. The failure rate was 12.8%. Failure was significantly correlated with low socioeconomic level (OR = 3), orphan status (OR = 4), age over 10 years (OR = 5), male gender (OR = 3), baseline viral load > or = 1,000,000 copies/mL (OR = 9), and poor compliance (OR = 37). Mortality in children who failed to respond to first-line ARV therapy was 25% due to the unavailability of a national second-line ARV therapy program. This study underlines the need for patient education to promote compliance and for creation of reference centers to prescribe ARV therapy to HIV-infected children including second-line ARV and genotyping.

  11. Modal Epistemology and Conceivability

    DEFF Research Database (Denmark)

    Philosophical argumentation often depends on modal facts, i.e. facts about what is possible, contingent, or necessary. For thought and cognition outside the domain of philosophy modal facts are also often decisive. It seems we have an easy access to modal facts, but how so? Through a presentation...... of the state-of-the-art in modal epistemology I wish to outline a research project based on conceivability that will try to explain how we come to know modal facts....

  12. Analysis of the efficacy and prognosis on first-line autologous hematopoietic stem cell transplantation of patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    邹徳慧

    2013-01-01

    Objective To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation(ASCT) for newly diagnosed patients with multiple myeloma(MM).Methods From January 2005 to

  13. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer

    OpenAIRE

    Socinski, M A

    2014-01-01

    Based on demonstrated favourable risk–benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability c...

  14. Predictive value of {sup 18}F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study

    Energy Technology Data Exchange (ETDEWEB)

    Caobelli, Federico [Medizinische Hochschule Hannover, Klinik fuer Nuklearmedizin, Hanover (Germany); Alongi, Pierpaolo [University of Milano-Bicocca, Nuclear Medicine Unit, Milan (Italy); IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Evangelista, Laura; Saladini, Giorgio [Veneto Institute of Oncology IOV - IRCCS, Radiotherapy and Nuclear Medicine Unit, Padua (Italy); Picchio, Maria [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Rensi, Marco; Geatti, Onelio [Hospital of Udine, Nuclear Medicine Department, Udine (Italy); Castello, Angelo; Laghai, Iashar [University of Florence, Nuclear Medicine Department, Florence (Italy); Popescu, Cristina E. [Niguarda Ca' Granda Hospital, Nuclear Medicine Department, Milan (Italy); Dolci, Carlotta; Crivellaro, Cinzia [University of Milan-Bicocca, Nuclear Medicine Department, San Gerardo Hospital, Tecnomed Foundation, Milan (Italy); Seghezzi, Silvia [Hospital of Treviglio, Nuclear Medicine Department, Treviglio, Bergamo (Italy); Kirienko, Margarita [University of Milano-Bicocca, Nuclear Medicine Unit, Milan (Italy); De Biasi, Vincenzo [Nuclear Medicine Department, Arcispedale Santa Maria Nuova, Reggio Emilia (Italy); Cocciolillo, Fabrizio [Catholic University of the Sacred Heart, Nuclear Medicine Department, Rome (Italy); Quartuccio, Natale [University of Messina, Nuclear Medicine Unit, Department of Biomedical Sciences and of Morphological and Functional Images, Messina (Italy); Collaboration: Young AIMN Working Group

    2016-03-15

    Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. {sup 18}F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of {sup 18}F-FDG PET/CT performed in the restaging process in a multicentre study. We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging {sup 18}F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUV{sub max} and SUV{sub mean}, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT. PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53 % vs 23 and 12 %, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25 % in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low

  15. Economic evaluation for first-line anti-hypertensive medicines: applications for the Philippines

    Directory of Open Access Journals (Sweden)

    Geroy Lester Sam Araneta

    2012-12-01

    Full Text Available Abstract Background Medicines to control hypertension, a leading cause of morbidity and mortality, are a major component of health expenditures in the Philippines. This study aims to review economic studies for first line anti-hypertensive medical treatment without co-morbidities; and discuss practical, informational and policy implications on the use of economic evaluation in the Philippines. Methods A systematic literature review was performed using the following databases: MEDLINE, EMBASE, BIOSIS, PubMed, The Cochrane Library, Health Economics Evaluations Database (HEED and the Centre for Reviews and Dissemination – NHS NICE. Six existing economic analytical frameworks were reviewed and one framework for critical appraisal was developed. Results Out of 1336 searched articles, 12 fulfilled the inclusion criteria. The studies were summarized according to their background characteristics (year, journal, intervention and comparators, objective/study question, target audience, economic study type, study population, setting and country and source of funding/conflict of interest and technical characteristics (perspective, time horizon, methodology/modeling, search strategy for parameters, costs, effectiveness measures, discounting, assumptions and biases, results, cost-effectiveness ratio, endpoints, sensitivity analysis, generalizability, strengths and limitations, conclusions, implications and feasibility and recommendations. The studies represented different countries, perspectives and stakeholders. Conclusions Diuretics were the most cost-effective drug class for first-line treatment of hypertension without co-morbidities. Although the Philippine Health Insurance Corporation may apply the recommendations given in previous studies (i.e. to subsidize diuretics, ACE inhibitors and calcium channel blockers, it is uncertain how much public funding is justified. There is an information gap on clinical data (transition probabilities, relative risks

  16. Electrochemotherapy as First Line Cancer Treatment: Experiences from Veterinary Medicine in Developing Novel Protocols.

    Science.gov (United States)

    Spugnini, E P; Azzarito, T; Fais, S; Fanciulli, M; Baldi, A

    2016-01-01

    Tumor microenvironment is one of the major obstacles to the efficacy of chemotherapy in cancer patients. The abnormal blood flow within the tumor results in uneven drug distribution. Electrochemotherapy (ECT) is a tumor treatment that adopts the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This allows the use of lipophobic drugs that frequently have a narrow therapeutic index maintaining at the same time a reduced patient morbidity and preserving appropriate anticancer efficacy. Its use in humans is addressed to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, and a standard operating procedure has been devised. On the other hand, in veterinary oncology this approach is gaining popularity, thus becoming a first line treatment for different cancer histotypes, in a variety of clinical conditions due to its high efficacy and low toxicity. This review summarizes the state of the art in veterinary oncology as a preclinical model and reports the new protocols in terms of drugs and therapy combination that have been developed.

  17. [Evidence on afatinib in patients progressing on a first-line treatment].

    Science.gov (United States)

    Artal Cortés, Ángel; Gimeno Pelegrín, Joaquín; Alejandro, María Álvarez

    2016-04-01

    After description of the importance of EGFR mutations in non-small cell lung cancer and confirmation that tyrosine-kinase inhibitors are more beneficial than chemotherapy in patients with EGFR+ tumours, treatment with one of these drugs has become the standard recommendation. Despite this advance, patients continue to progress and consequently there is a need to search for alternative treatments. Some studies have analysed afatinib activity after first-generation TKI therapy, as well as its administration in combination with conventional chemotherapy. Afatinib produces significant response rates and progression-free survival times after the development of clinical resistance, which are independent of the presence of the T790M resistance mutation and can be attributed to continued pan-HER inhibition. In addition to the initial clinical trial, LUX-LUNG-1, data are available from the use of afatinib in routine clinical practice, within extended use programs. Overall, response rates of between 7 and 15% can be expected with a duration of approximately 24 months and a median progression-free time of about 4 months. A study combining afatinib with cetuximab has obtained a high response rate. Afatinib toxicity in second-line treatment is similar to that appears when the drug is used as first-line therapy (mainly mucocutaneous and diarrhoea) and can be managed with routine measures. In conclusion, afatinib should be considered as a treatment option in patients with EGFR mutations who show disease progression after a first tyrosine-kinase inhibitor.

  18. Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer.

    Science.gov (United States)

    Feliu, J; Safont, M J; Salud, A; Losa, F; García-Girón, C; Bosch, C; Escudero, P; López, R; Madroñal, C; Bolaños, M; Gil, M; Llombart, A; Castro-Carpeño, J; González-Barón, M

    2010-05-11

    The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance

  19. PROGNOSTIC FACTORS FOR SURVIVAL IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH FIRST - LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2017-05-01

    Full Text Available Objective: The aim of this study was to investigate the prognostic significance for survival of certain clinical and pathological factors in patients with advanced or metastatic colorectal carcinoma (CRC treated with first- line chemotherapy. Methods: From 2002 to 2011 seventy- four consecutive patients with advanced or metastatic CRC, treated in UMHAT- Dr. G. Stranski, Department of Medical Oncology entered the study. Some patient’s characteristics, hematological and pathological parameters, were evaluated for their role as predictors of overall survival. The therapeutic regimens included FOLFOX or FOlFIRI. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment characteristics as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: In multivariate analysis a significant correlation was exhibited between survival, poor performance status and multiple sites of metastasis. Variables significantly associated with overall survival in univariate analysis were performance status>1, thrombocytosis, anemia and number of metastatic sites >1. Conclusion: These results indicated that poor performance status, anemia, thrombocytosis as well as multiple site of metastasis could be useful prognostic factors in patients with metastatic CRC.

  20. Pertuzumab: in the first-line treatment of HER2-positive metastatic breast cancer.

    Science.gov (United States)

    Keating, Gillian M

    2012-02-12

    The humanized monoclonal antibody pertuzumab is the first in a new class of drugs, the human epidermal growth factor receptor (HER) dimerization inhibitors. Given that pertuzumab binds to a different epitope of the HER2 extracellular domain than trastuzumab, combination therapy with pertuzumab plus trastuzumab may result in more comprehensive blockade of HER2 signalling than can be achieved with trastuzumab alone. The efficacy of adding pertuzumab to trastuzumab plus docetaxel for the first-line treatment of HER2-positive metastatic breast cancer was demonstrated in the randomized, double-blind, multinational, phase III CLEOPATRA trial. Both independently assessed progression-free survival (primary endpoint) and investigator-assessed progression-free survival were significantly improved in patients receiving pertuzumab plus trastuzumab and docetaxel compared with those receiving placebo plus trastuzumab and docetaxel. The prespecified interim analysis of survival revealed a strong trend towards a survival benefit associated with pertuzumab, although this was not considered statistically significant. The objective response rate was higher with pertuzumab than with placebo. Intravenous pertuzumab had an acceptable tolerability profile when added to trastuzumab and docetaxel in the CLEOPATRA trial.

  1. First-line therapy of chronic myeloid leukemia – focus on dasatinib

    Directory of Open Access Journals (Sweden)

    Amrein PC

    2012-04-01

    Full Text Available Philip C AmreinHematology-Oncology, Massachusetts General Hospital, Boston, USAAbstract: Dasatinib is a broad spectrum, ATP-competitive, tyrosine kinase inhibitor with low nM activity against Bcr-Abl, Src, and other tyrosine kinases. This activity has allowed dasatinib to emerge as one of the most effective agents in the treatment of chronic myeloid leukemia (CML, and dasatinib has become the third drug over the past 10 years to be FDA approved for first line therapy in this setting. This review consists of papers and reports that recount the recent dramatic progress that has been made in the understanding of CML on a molecular basis leading up to the new targeted therapies, especially the use of dasatinib. As with any drug, treatment with dasatinib has risks and side effects, especially pleural effusions and anti-platelet effects, as outlined in recently published studies. Of interest are the reports of alternative doses and schedules that may be able to circumvent some of these side effects without compromising the effectiveness of this drug. This review outlines the mode of action, pharmacology, effectiveness, and safety of dasatinib in the treatment of CML, and by comparing dasatinib directly with the other tyrosine kinase inhibitors effective in CML, it describes the place in therapy that dasatinib currently holds.Keywords: dasatinib, CML, chronic myeloid leukemia 

  2. [{sup 11}C]Choline positron emission tomography/computed tomography for staging and restaging of patients with advanced prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tuncel, Murat; Souvatzoglou, Michael; Herrmann, Ken [Department of Nuclear Medicine, Klinikum rechts der lsar, Technische Universitaet Muenchen, 81675 Munich (Germany); Stollfuss, Jens [Department of Radiology, Technische Universitaet Muenchen, 81675 Munich (Germany); Schuster, Tibor [Department of Statistics, Technische Universitaet Muenchen, 81675 Munich (Germany); Weirich, Gregor [Department of Pathology, Technische Universitaet Muenchen, 81675 Munich (Germany); Wester, Hans-Juergen; Schwaiger, Markus [Department of Nuclear Medicine, Klinikum rechts der lsar, Technische Universitaet Muenchen, 81675 Munich (Germany); Krause, Bernd J. [Department of Nuclear Medicine, Klinikum rechts der lsar, Technische Universitaet Muenchen, 81675 Munich (Germany)], E-mail: bernd-joachim.krause@tum.de

    2008-08-15

    Introduction: To evaluate [{sup 11}C]Choline positron emission tomography (PET)/computed tomography (CT) for staging and restaging of patients with advanced prostate cancer and to compare the diagnostic performance of PET, CT and PET/CT. Methods: Forty-five consecutive patients with advanced prostate cancer underwent [{sup 11}C]Choline-PET/CT between 5/2004 and 2/2006. Results: Overall, 295 lesions were detected: PET alone, 178 lesions; diagnostic CT, 221 lesions; PET/CT (low-dose CT), 272 lesions; PET/CT (diagnostic CT), 295 lesions. Two thirds of the lesions were located in the bone; one third in the prostate, lymph nodes, periprostatic tissue and soft tissue (lung, liver). The use of diagnostic CT did not result in a statistically significant difference with respect to lesion localization certainty and lesion characterization (P=.063, P=.063). PET-negative but PET/CT-positive lesions were mostly localized in the bone (78%, 91/117) as were PET-positive and CT-negative lesions (72%, 53/74). Of the latter, 91% (48/53) represented bone marrow and 9% (5/53) cortical involvement. Conclusions: Staging and restaging with [{sup 11}C]Choline PET/CT in patients with advanced prostate cancer improve the assessment of local and regional recurrent as well as metastatic disease including skeletal manifestations. [{sup 11}C]Choline PET/CT (with a low-dose CT) results in improved localization and lesion characterization. [{sup 11}C]Choline PET/CT provides an added value for skeletal manifestations. [{sup 11}C]Choline PET/CT changed disease management in 11 (24%) of 45 patients with advanced prostate cancer.

  3. A Comparison between 18F-FDG PET/CT Imaging and Biological and Radiological Findings in Restaging of Hepatoblastoma Patients

    Science.gov (United States)

    Treglia, Giorgio; Pagano, Manuela; Fania, Piercarlo; Basso, Maria Eleonora; Fagioli, Franca; Ficola, Umberto

    2013-01-01

    Background. In this study we retrospectively evaluated if 18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serum α-FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/or α-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. Results. α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but 18F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. 18F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results. Conclusions. 18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients. PMID:24063012

  4. A Comparison between 18F-FDG PET/CT Imaging and Biological and Radiological Findings in Restaging of Hepatoblastoma Patients

    Directory of Open Access Journals (Sweden)

    Angelina Cistaro

    2013-01-01

    Full Text Available Background. In this study we retrospectively evaluated if 18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years surgically treated for hepatoblastoma were followed up by clinical examination, serum α-FP monitoring, and US. CI (CT or MRI and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB were carried out for final confirmation if the results of CI, PET/CT, and/or α-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. Results. α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but 18F-FDG-PET/CT provided a better definition of disease extent; in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. 18F-FDG-PET/CT showed an agreement of 100% (8/8 with FNAB results. Conclusions. 18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients.

  5. Experimental modal analysis

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten

    This technical report concerns the basic theory and principles for experimental modal analysis. The sections within the report are: Output-only modal analysis software (section 1.1), general digital analysis (section 1.2), basics of structural dynamics and modal analysis (section 1.3) and system ...

  6. Cost-effectiveness of endoscopic sphenopalatine artery ligation versus nasal packing as first-line treatment for posterior epistaxis.

    Science.gov (United States)

    Dedhia, Raj C; Desai, Shamit S; Smith, Kenneth J; Lee, Stella; Schaitkin, Barry M; Snyderman, Carl H; Wang, Eric W

    2013-07-01

    The advent of endoscopic sphenopalatine artery ligation (ESPAL) for the control of posterior epistaxis provides an effective, low-morbidity treatment option. In the current practice algorithm, ESPAL is pursued after failure of posterior packing. Given the morbidity and limited effectiveness of posterior packing, we sought to determine the cost-effectiveness of first-line ESPAL compared to the current practice model. A standard decision analysis model was constructed comparing first-line ESPAL and current practice algorithms. A literature search was performed to determine event probabilities and published Medicare data largely provided cost parameters. The primary outcomes were cost of treatment and resolution of epistaxis. One-way sensitivity analysis was performed for key parameters. Costs for the first-line ESPAL arm and the current practice arm were $6450 and $8246, respectively. One-way sensitivity analyses were performed for key variables including duration of packing. The baseline difference of $1796 in favor of the first-line ESPAL arm was increased to $6263 when the duration of nasal packing was increased from 3 to 5 days. Current practice was favored (cost savings of $437 per patient) if posterior packing duration was decreased from 3 to 2 days. This study demonstrates that ESPAL is cost-saving as first-line therapy for posterior epistaxis. Given the improved effectiveness and patient comfort of ESPAL compared to posterior packing, ESPAL should be offered as an initial treatment option for medically stable patients with posterior epistaxis. © 2013 ARS-AAOA, LLC.

  7. Clinical experience with intravenous valproate as first-line treatment of status epilepticus and seizure clusters in selected populations.

    Science.gov (United States)

    Lapenta, Leonardo; Morano, Alessandra; Casciato, Sara; Fanella, Martina; Fattouch, Jinane; Vaudano, Anna Elisabetta; Gregori, Bruno; Vanacore, Nicola; Manfredi, Mario; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2014-01-01

    The aim of this study was to evaluate the efficacy and safety of intravenous valproate (i.v. VPA) as first-line treatment of status epilepticus (SE) and seizure clusters in selected patient populations. We enrolled 23 patients (11 females and 12 males; mean age: 61 years) with SE who received i.v. VPA as first-line therapy (25 mg/kg in 100 mL saline infused over 15 min). ECG tracing was monitored before, during, and after infusion. Liver function and serum ammonia tests were conducted after 24 and 72 h of treatment. We evaluate the response of SE to i.v. therapy and short-term outcome. In 15 out of 23 patients (65%), i.v. VPA was effective. In our population, we retrospectively identified three different subgroups: patients with cardiorespiratory comorbidities discouraging the use of traditional SE first-line drugs, patients with specific epileptic subsyndromes (such as idiopathic generalized epilepsy), and patients affected by psycho-organic syndromes. No significant adverse effects were detected. Our study shows the clinical relevance of i.v. VPA as first-line therapy of SE in patients with medical conditions contraindicating the use of traditional first-line antiepileptic drugs for SE, and in those presenting with specific forms of SE.

  8. Economic Outcomes of First-Line Regimen Switching Among Stable Patients with HIV.

    Science.gov (United States)

    Rosenblatt, Lisa; Buikema, Ami R; Seare, Jerry; Bengtson, Lindsay G S; Johnson, Jonathan; Cao, Feng; Villasis-Keever, Angelina

    2017-07-01

    Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months. Those with evidence of pregnancy or HIV-2 were excluded. Patients who underwent an ART change were assigned to a switcher cohort; a nonswitcher cohort was then generated by matching up to 20 nonswitchers for each switcher, with replacement. The index date was the date of the first ART change for switchers and was the claim date closest to the corresponding switcher's switch date for nonswitchers. Patient characteristics at baseline and post-index annualized health care utilization and costs were analyzed descriptively and with multivariable models. Analyses were performed in the full population and among patients designated as virologically stable (had undetectable viral ribonucleic acid [RNA] for 90 days pre-index) and virologically and clinically stable (had undetectable viral RNA and no apparent clinical reason for switching ART). The study population consisted of 6,983 individuals, which included 927 switchers (168 virologically stable; 55 virologically+clinically stable), who were matched with replacement with 18,511 nonswitcher comparators. The switcher cohort was 88.8% male (mean age 43.8 years). Mean preindex and follow-up treatment durations for switchers and nonswitchers were 1.8 years and 1.5 years, respectively; demographic characteristics, pre-index treatment duration, and follow-up duration were similar between cohorts. Significantly more

  9. Quadruple therapy with moxifloxacin and bismuth for first-line treatment of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Antonio Francesco Ciccaglione; Luigina Cellini; Laurino Grossi; Leonardo Marzio

    2012-01-01

    AIM:To compare triple therapy vs quadruple therapy for 10 d as first-line treatment of Helicobacterpylori (H.pylori) infection.METHODS:Consecutive H.pylori positive patients never treated in the past for this infection were randomly treated with triple therapy of pantoprazole (PAN) 20 mg bid,amoxicillin (AMO) 1 g bid and moxifloxacin (MOX) 400 mg bid for 10 d (PAM) or with quadruple therapy of PAN 20 mg bid,AMO 1 g bid,MOX 400 mg bid and bismuth subcitrate 240 mg bid for 10 d (PAMB).All patients were found positive at 13 C-Urea breath test (UBT) performed within ten days prior to the start of the study.A successful outcome was confirmed with an UBT performed 8 wk after the end of treatment.x2 analysis was used for statistical comparison.Per protocol (PP) and intention-to-treat (ITT) values were also calculated.RESULTS:Fifty-seven patients were enrolled in the PAM group and 50 in the PAMB group.One patient in each group did not return for further assessment.Eradication was higher in the PAMB group (negative:46 and positive:3) vs the PAN group (negative:44 and positive:12).The H.pylori eradication rate was statistically significantly higher in the PAMB group vs the PAM group,both with the PP and ITT analyses (PP:PAMB 93.8%,PAM 78.5%,P < 0.02; ITT:PAMB 92%,PAM 77.1%,P <0.03).CONCLUSION:The addition of bismuth subcitrate can be considered a valuable adjuvant to triple therapy in those areas where H.pylori shows a high resistance to fluoroquinolones.

  10. Cost Effectiveness of Ofatumumab Plus Chlorambucil in First-Line Chronic Lymphocytic Leukaemia in Canada.

    Science.gov (United States)

    Herring, William; Pearson, Isobel; Purser, Molly; Nakhaipour, Hamid Reza; Haiderali, Amin; Wolowacz, Sorrel; Jayasundara, Kavisha

    2016-01-01

    Our objective was to estimate the cost effectiveness of ofatumumab plus chlorambucil (OChl) versus chlorambucil in patients with chronic lymphocytic leukaemia for whom fludarabine-based therapies are considered inappropriate from the perspective of the publicly funded healthcare system in Canada. A semi-Markov model (3-month cycle length) used survival curves to govern progression-free survival (PFS) and overall survival (OS). Efficacy and safety data and health-state utility values were estimated from the COMPLEMENT-1 trial. Post-progression treatment patterns were based on clinical guidelines, Canadian treatment practices and published literature. Total and incremental expected lifetime costs (in Canadian dollars [$Can], year 2013 values), life-years and quality-adjusted life-years (QALYs) were computed. Uncertainty was assessed via deterministic and probabilistic sensitivity analyses. The discounted lifetime health and economic outcomes estimated by the model showed that, compared with chlorambucil, first-line treatment with OChl led to an increase in QALYs (0.41) and total costs ($Can27,866) and to an incremental cost-effectiveness ratio (ICER) of $Can68,647 per QALY gained. In deterministic sensitivity analyses, the ICER was most sensitive to the modelling time horizon and to the extrapolation of OS treatment effects beyond the trial duration. In probabilistic sensitivity analysis, the probability of cost effectiveness at a willingness-to-pay threshold of $Can100,000 per QALY gained was 59 %. Base-case results indicated that improved overall response and PFS for OChl compared with chlorambucil translated to improved quality-adjusted life expectancy. Sensitivity analysis suggested that OChl is likely to be cost effective subject to uncertainty associated with the presence of any long-term OS benefit and the model time horizon.

  11. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    Science.gov (United States)

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection.

  12. Proteinuria with first-line therapy of metastatic renal cell cancer.

    Science.gov (United States)

    Land, Josiah D; Chen, Adrienne H; Atkinson, Bradley J; Cauley, Diana H; Tannir, Nizar M

    2016-04-01

    Vascular endothelial growth factor receptor inhibitors, mammalian target of rapamycin inhibitors, and tyrosine kinase inhibitors are approved for metastatic renal cell cancer. Proteinuria can occur, but there is limited data regarding the incidence, monitoring, and management in metastatic renal cell cancer patients. Our primary objective was to describe the incidence and severity of proteinuria in metastatic renal cell cancer patients treated in the first-line setting with pazopanib, bevacizumab, or everolimus. We conducted a retrospective review of patients with metastatic renal cell cancer enrolled from January 2011-April 2013 in a phase II trial. Baseline and toxicity data were extracted from the electronic medical record. Descriptive statistics were used. In all, 129 patients were eligible for analysis. The overall incidence of proteinuria was 81%, with most events being Grade 1 or 2. The incidence of proteinuria was 80% (n = 35) for pazopanib, 64% (n = 25) for bevacizumab, and 96% (n = 44) for everolimus. At peak proteinuria, 80% (n = 28), 64% (n = 16), and 80% (n = 35) of patients on pazopanib, bevacizumab, and everolimus, respectively, were managed with continued monitoring at the same dose. The overall incidence of Grades 3 and 4 events was 24% (n = 6) and found in the bevacizumab group. A high incidence of proteinuria with minor severity within each class was demonstrated. It may be reasonable to continue therapy at the same dose for Grade 1 or 2 proteinuria. Treatment modification or discontinuation of therapy may be warranted with Grade 3 or 4 proteinuria. © The Author(s) 2014.

  13. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Science.gov (United States)

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Husserl’s Modal Sense of Evidence: Modality versus Modalization

    Directory of Open Access Journals (Sweden)

    Ivana Anton

    2013-12-01

    Full Text Available Phenomenological evidence has been characterized as fulfillment of a meaning intention, comprehension that tends to assimilate evidence to fulfilled consciousness, without making justice to the essential and mutual implication of emptiness and fullness that constitutes it out of its horizontic-intentional kind. The horizon, typically configured, offers the field of possible fulfillment; that is why it can be said that evidence takes place in a consciousness of possibility, namely, a modal one, though in an originary material and not doxic or positional sense,because it is the first one that is incumbent upon relationships of fulfillment. Modality that essentially characterizes evidence does not reveal itself then in the possible modalization as positional modification of a unitary content, but in its “outlined” material configuration of fullness and emptiness that gives somethingas something referring to other possibilities as moments of its own validity.

  15. Operational Modal Analysis Tutorial

    DEFF Research Database (Denmark)

    Brincker, Rune; Andersen, Palle

    analysis in an easier way and in many cases more effectively than traditional modal analysis methods. It can be applied for modal testing and analysis on a wide range of structures and not only for problems generally investigated using traditional modal analysis, but also for those requiring load......In this paper the basic principles in operational modal testing and analysis are presented and discussed. A brief review of the techniques for operational modal testing and identification is presented, and it is argued, that there is now a wide range of techniques for effective identification...... estimation, vibration level estimation and fatigue analysis....

  16. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer.

    Science.gov (United States)

    Socinski, M A

    2014-10-01

    Based on demonstrated favourable risk-benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability compared with solvent-based paclitaxel-carboplatin in a phase iii trial. This review focuses on the evolution of first-line taxane therapy for advanced nsclc and the new options and advances in taxane therapy that might address unmet needs in advanced nsclc.

  17. A Study on Internal Service Recovery Strategy Using CIT from the First Line Staff’s Perspective

    Institute of Scientific and Technical Information of China (English)

    Guoqing HUANG; Pengfei XIE; Hong SHU

    2014-01-01

    Service is a special product. It is intangible and unstored, so service er-rors are not avoided. Once service errors appear, the first line staffs who keep di-rect touch with customers wil play an important role in service recovery. The staffs' negative emotions during the recovery service should be recovered by internal ser-vice recovery. In this paper, critical incident technique is applied to analyse the re-covery strategies expected by the first line staff and the internal service recovery strategies such as inspiring, authorization, training and psychology service are put forward. the strategy most expected by the staff is reward.

  18. Responsibilities and commitment of top management and first line management in organizational-level interventions - what difference does it make?

    DEFF Research Database (Denmark)

    Gish, Liv; Ipsen, Christine; Poulsen, Signe

    -house facilitators. The involvement of both top management and first line management gave rise to review the differences in responsibilities and commitment between the two and the interaction between them. The study showed that a prerequisite for an optimal implementation was an initial matching of expectations...... and make the necessary adjustments, integrate the selected intervention activities in the daily operations, and make the value of the changes visible. In the companies with least implementation success we observed that the first line managers failed in committing to the project. These managers prioritized...

  19. A survey of ATRIPLA use in clinical practice as first-line therapy in HIV-positive persons in Europe

    DEFF Research Database (Denmark)

    Mocroft, A; Reiss, P; Rakhmanova, A

    2014-01-01

    ATRIPLA is licensed for use only in HIV-positive persons whose viral loads therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012. 96/112 clinics (85.7 %) completed the survey. Recommendations...... when initiating first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %), a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7 clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and least common in Eastern Europe (2....../31 clinics; 6.5 %; p therapy, despite EMA recommendations....

  20. Moxifloxacin plus standard first-line therapy in the treatment of pulmonary tuberculosis: A meta-analysis.

    Science.gov (United States)

    Chen, Zhi; Liang, Jian-Qin; Wang, Jin-He; Feng, Shi-Sheng; Zhang, Guang-Yu

    2015-07-01

    The fluoroquinolone moxifloxacin has potent activity against Mycobacterium tuberculosis and has been recommended by the guidelines for the treatment of pulmonary tuberculosis (TB). Monotherapy is not recommended by the guidelines and only a few studies have evaluated the efficacy and safety of moxifloxacin plus standard first-line therapy in treating TB. The purpose of this meta-analysis was to further investigate the efficacy and safety of moxifloxacin plus standard therapy compared with standard therapy alone in treating patients with pulmonary TB. Medline, Cochrane, EMBASE and Google Scholar (until February 12, 2015) were searched for studies that evaluated the clinical efficacy and tolerability of moxifloxacin in the treatment of pulmonary TB. Rate of culture conversion and serious adverse events (SAEs) were assessed. Risk of bias and sensitivity analysis, using the leave-one-out approach, was used to assess the robustness of the findings. Six studies were included in the meta-analysis which covered 2056 patients with pulmonary TB. For all included studies, the drug regimens at least contained rifampicin and pyrazinamide and the length of treatment was at least eight weeks. The odds ratio (OR) for the negative culture rate for moxifloxacin plus first-line medications compared first-line medications alone (the control group) was 1.60 with 95% CI in 0.93-2.74 (P = 0.089), indicating the moxifloxacin plus first-line medications had no significantly greater rate of culture conversion compared with first-line medication alone. The odds ratio of SAEs for moxifloxacin plus first-line medications compared with first-line medications alone found no difference in rate of SAEs between treatment groups (OR = 0.94, P = 0.862). In conclusion, our meta-analysis suggests that there was a trend for the addition of moxifloxacin to standard first-line therapy for non-drug resistant TB resulted to increase the rate of culture conversion but this effect requires confirmation

  1. Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda

    Directory of Open Access Journals (Sweden)

    Sempa Joseph

    2012-09-01

    Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

  2. Survival outcomes for first-line antiretroviral therapy in India's ART program.

    Science.gov (United States)

    Dandona, Rakhi; Rewari, Bharat B; Kumar, G Anil; Tanwar, Sukarma; Kumar, S G Prem; Vishnumolakala, Venkata S; Duber, Herbert C; Gakidou, Emmanuela; Dandona, Lalit

    2016-10-11

    Little is known about survival outcomes of HIV patients on first-line antiretroviral therapy (ART) on a large-scale in India, or facility level factors that influence patient survival to guide further improvements in the ART program in India. We examined factors at the facility level in addition to patient factors that influence survival of adult HIV patients on ART in the publicly-funded ART program in a high- and a low-HIV prevalence state. Retrospective chart review in public sector ART facilities in the combined states of Andhra Pradesh and Telangana (APT) before these were split in 2014 and in Rajasthan (RAJ), the high- and a low-HIV prevalence states, respectively. Records of adults initiating ART between 2007-12 and 2008-13 in APT and RAJ, respectively, were reviewed and facility-level information collected at all ART centres and a sample of link ART centres. Survival probability was estimated using Kaplan-Meier method, and determinants of mortality explored with facility and patient-level factors using Cox proportional hazard model. Based on data from 6581 patients, the survival probability of ART at 60 months was 76.3 % (95 % CI 73.0-79.2) in APT and 78.3 % (74.4-81.7) in RAJ. The facilities with cumulative ART patient load above the state average had lower mortality in APT (Hazard ratio [HR] 0.74, 0.57-0.95) but higher in RAJ (HR 1.37, 1.01-1.87). Facilities with higher proportion of lost to follow-up patients in APT had higher mortality (HR 1.47, 1.06-2.05), as did those with higher ART to pre-ART patient ratio in RAJ (HR 1.62, 1.14-2.29). In both states, there was higher hazard for mortality in patients with CD4 count 100 cells/mm(3) or less at ART initiation, males, and in patients with TB co-infection. These data from the majority of facilities in a high- and a low-HIV burden state of India over 5 years reveal reasonable and similar survival outcomes in the two states. The facilities with higher ART load in the longer established ART program in

  3. The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer.

    Science.gov (United States)

    McLachlan, J; Boussios, S; Okines, A; Glaessgen, D; Bodlar, S; Kalaitzaki, R; Taylor, A; Lalondrelle, S; Gore, M; Kaye, S; Banerjee, S

    2017-03-01

    Despite recent advances in the primary and secondary prevention of cervical cancer, a significant number of women present with or develop metastatic disease. There is currently no consensus on the standard of care for second-line systemic treatment of recurrent/metastatic cervical cancer. The purpose of this study was to evaluate the second-line systemic therapy used and the associated outcomes in a single cancer centre. A retrospective review of patients with cervical cancer who received one or more lines of treatment for recurrent or metastatic cervical cancer at the Royal Marsden Hospital between 2004 and 2014 was carried out. The primary objective was to establish the types of second-line systemic treatment used. Secondary end points included objective response rate, progression-free survival and overall survival after second-line therapy. In total, 75 patients were included in the study; 53 patients (70.7%) received second-line therapy for recurrent/metastatic disease. The most common second-line therapy was weekly paclitaxel (28.3%). Carboplatin-based chemotherapy (24.5%), targeted agent monotherapy within clinical trials (22.6%), docetaxel-based chemotherapy (13.2%), topotecan (9.4%) and gemcitabine (1.9%) were also used. The objective response rate to second-line therapy was 13.2%, which included three partial responses to carboplatin and paclitaxel, two partial responses to docetaxel-based chemotherapy, one partial response to weekly paclitaxel and one partial response to cediranib. Twenty-two patients (41.5%) achieved stable disease at 4 months. The median progression-free survival for women treated with second-line therapy was 3.2 months (95% confidence interval 2.1-4.3) and median overall survival was 9.3 months (95% confidence interval 6.4-12.5). Thirty-nine per cent of patients received third-line therapy. Seventy per cent of patients treated with first-line systemic therapy for recurrent/metastatic cervical cancer subsequently received second

  4. Optimized Flat-Detector CT in Stroke Imaging: Ready for First-Line Use?

    Science.gov (United States)

    Eckert, Matthias; Gölitz, Philipp; Lücking, Hannes; Struffert, Tobias; Knossalla, Frauke; Doerfler, Arnd

    2017-01-01

    Using flat-detector CT (FD-CT) for stroke imaging has the advantage that both diagnostic imaging and endovascular therapy can be performed directly within the Angio Suite without any patient transfer and time delay. Thus, stroke management could be speeded up significantly, and patient outcome might be improved. But as precondition for using FD-CT as primary imaging modality, a reliable exclusion of intracranial hemorrhage (ICH) has to be possible. This study aimed to investigate whether optimized native FD-CT, using a newly implemented reconstruction algorithm, may reliably detect ICH in stroke patients. Additionally, the potential to identify ischemic changes was evaluated. Cranial FD-CT scans were obtained in 102 patients presenting with acute ischemic stroke (n = 32), ICH (n = 45) or transient ischemic attack (n = 25). All scans were reconstructed with a newly implemented half-scan cone-beam algorithm. Two experienced neuroradiologists, unaware of clinical findings, evaluated independently the FD-CTs screening for hemorrhage or ischemic signs. The findings were correlated to CT, and rater and inter-rater agreement was assessed. FD-CT demonstrated high sensitivity (95-100%) and specificity (100%) in detecting intracerebral and intraventricular hemorrhage (IVH). Overall, interobserver agreement (κ = 0.92) was almost perfect and rater agreement to CT highly significant (r = 0.81). One infratentorial ICH and 10 or 11 of 22 subarachnoid hemorrhages (SAHs) were missed of whom 7 were perimesencephalic. The sensitivity for detecting acute ischemic signs was poor in blinded readings (0 or 25%, respectively). Optimized FD-CT, using a newly implemented reconstruction algorithm, turned out as a reliable tool for detecting supratentorial ICH and IVH. However, detection of infratentorial ICH and perimesencephalic SAH is limited. The potential of FD-CT in detecting ischemic changes is poor in blinded readings. Thus, plain FD-CT seems insufficient as a standalone modality in

  5. Clinical evidence for caspofungin monotherapy in the first-line and salvage therapy of invasive Aspergillus infections.

    Science.gov (United States)

    Heinz, Werner J; Buchheidt, Dieter; Ullmann, Andrew J

    2016-08-01

    In 2001, caspofungin received market authorisation by the FDA and EMA and is globally licensed for several indications, including candidiasis, empirical antifungal therapy in patients with neutropenic fever of unknown origin and treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B or itraconazole. Despite the lack of phase III data in first-line treatment of invasive aspergillosis, increasing evidence supports the use of first-line therapy. Here, we analyse the evidence of therapeutic activity, represented by favourable response rates, of caspofungin for invasive aspergillosis. A systematic literature search was conducted to identify international presentations and papers reporting monotherapy with caspofungin. Efficacy data are summarised separately for first-line and salvage therapy. Thirty-one papers and published abstracts reported caspofungin therapy for aspergillosis. Fifteen full papers and two abstracts fulfilled the criteria of reporting significant outcome data for caspofungin monotherapy for invasive aspergillosis. Consistent with other analyses and the known safety profile, few adverse events and associated terminations of caspofungin medication have been reported. Although a randomised, comparative, prospective study using caspofungin in this indication is still lacking, growing evidence supports the efficacy of this echinocandin not only for salvage but also for first-line therapy.

  6. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu;

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  7. Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma

    DEFF Research Database (Denmark)

    Maughan, Benjamin L; Agarwal, Neeraj; Hussain, Syed A;

    2013-01-01

    Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC...

  8. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer

    NARCIS (Netherlands)

    Piccart-Gebhart, Martine J.; Burzykowski, Tomasz; Buyse, Marc; Sledge, George; Carmichael, James; Lueck, Hans-Joachim; Mackey, John R.; Nabholtz, Jean-Marc; Paridaens, Robert; Biganzoli, Laura; Jassem, Jacek; Bontenbal, Marijke; Bonneterre, Jacques; Chan, Stephen; Basaran, Gul Atalay; Therasse, Patrick

    2008-01-01

    Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, prog

  9. Operational Modal Analysis Tutorial

    OpenAIRE

    Brincker, Rune; Andersen, Palle

    2007-01-01

    In this paper the basic principles in operational modal testing and analysis are presented and discussed. A brief review of the techniques for operational modal testing and identification is presented, and it is argued, that there is now a wide range of techniques for effective identification of modal parameters of practical interest - including the mode shape scaling factor - with a high degree of accuracy. It is also argued that the operational technology offers the user a number of advanta...

  10. Modal extension rule

    Institute of Scientific and Technical Information of China (English)

    WU Xia; SUN Jigui; LIN Hai; FENG Shasha

    2005-01-01

    Modal logics are good candidates for a formal theory of agents. The efficiency of reasoning method in modal logics is very important, because it determines whether or not the reasoning method can be widely used in systems based on agent. In this paper,we modify the extension rule theorem proving method we presented before, and then apply it to P-logic that is translated from modal logic by functional transformation. At last, we give the proof of its soundness and completeness.

  11. Nanoscaled hydrated antimony (V oxide as a new approach to first-line antileishmanial drugs

    Directory of Open Access Journals (Sweden)

    Franco AMR

    2016-12-01

    Full Text Available Antonia MR Franco,1 Iryna Grafova,2 Fabiane V Soares,1,3 Gennaro Gentile,4 Claudia DC Wyrepkowski,1,3 Marcos A Bolson,5 Ézio Sargentini Jr,5 Cosimo Carfagna,4 Markku Leskelä,2 Andriy Grafov2 1Laboratory of Leishmaniasis and Chagas Disease, National Institute of Amazonian Research (INPA, Manaus, Amazonas, Brazil; 2Department of Chemistry, University of Helsinki, Helsinki, Finland; 3Multi-Institutional Post-Graduate Program in Biotechnology, Federal University of Amazonas, Manaus, Amazonas, Brazil; 4Institute for Polymers, Composites, and Biomaterials, National Research Council, Pozzuoli, Naples Province, Italy; 5Laboratory of Environmental Chemistry, National Institute of Amazonian Research (INPA, Manaus, Amazonas, Brazil Background: Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V complexes are commercialized as sodium stibogluconate (Pentostam® and meglumine antimoniate (MA (Glucantime®. Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb5+ toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5⋅nH2O nanoparticles (NPs, instead of molecular drugs. Methodology/principal findings: Sb2O5⋅nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5⋅nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35–45 nm. In vitro tests demonstrated a 2.5–3 times higher antiparasitic activity of Sb (V nanohybrid hydrosols

  12. Tratamento de primeira linha no Mieloma Múltiplo First line treatment in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Gisele W. B. Colleoni

    2007-03-01

    Full Text Available A presente revisão tem por objetivo avaliar o estado atual do tratamento de primeira linha dos pacientes com MM. O paciente com MM assintomático não deve receber tratamento ao diagnóstico, mas apenas quando surgirem indicações. Para o paciente sintomático (anemia, hipercalcemia, alteração da função renal, presença de lesões líticas ou plasmocitoma extramedular, aumento progressivo do componente-M no soro e/ou urina, o tratamento deverá ser rapidamente instituído. Aqueles pacientes com menos de 65-70 anos, com bom performance status, sem comorbidades e com função renal próxima do normal são potencialmente candidatos à consolidação com altas doses de quimioterapia seguidas de transplante autólogo de células-tronco hematopoéticas. Portanto, não devem utilizar drogas alquilantes para evitar prejuízos à mobilização das células-tronco. São opções: dexametasona, VAD e talidomida (com ou sem dexametasona. Os pacientes com mais de 65-70 anos, com performance status ruim, comorbidades e com função renal alterada podem receber tratamento com agentes alquilantes (por exemplo, melfalano e prednisona, com ou sem talidomida pois não serão submetidos a transplante. O principal objetivo nesses casos é atingir resposta com mínima toxicidade.The aim of this review is to evaluate the current status of first line treatment in multiple myeloma. Asymptomatic patients should not receive treatment at diagnosis. However, symptomatic patients (anemia, hypercalcemia, deterioration in renal function, lytic lesions or extramedullary plasmacytomas, increase of M-component in serum or urine should receive treatment as soon as possible. Patients younger than 65-70 years old with good performance status, no concurrent diseases and normal renal function are possible candidates for consolidation using high-dose chemotherapy followed by stem-cell transplantation. Therefore, they should not receive drugs that could potentially interfere with

  13. Advances in Modal Logic

    DEFF Research Database (Denmark)

    Modal logic is a subject with ancient roots in the western logical tradition. Up until the last few generations, it was pursued mainly as a branch of philosophy. But in recent years, the subject has taken new directions with connections to topics in computer science and mathematics. This volume...... is the proceedings of the conference of record in its fi eld, Advances in Modal Logic. Its contributions are state-of-the-art papers. The topics include decidability and complexity results for specifi c modal logics, proof theory of modal logic, logics for reasoning about time and space, provability logic, dynamic...... epistemic logic, and the logic of evidence....

  14. Sequential versus standard triple first-line therapy for Helicobacter pylori eradication.

    Science.gov (United States)

    Nyssen, Olga P; McNicholl, Adrian G; Megraud, Francis; Savarino, Vincenzo; Oderda, Giuseppina; Fallone, Carlo A; Fischbach, Lori; Bazzoli, Franco; Gisbert, Javier P

    2016-06-28

    Non-bismuth quadruple sequential therapy (SEQ) comprising a first induction phase with a dual regimen of amoxicillin and a proton pump inhibitor (PPI) for five days followed by a triple regimen phase with a PPI, clarithromycin and metronidazole for another five days, has been suggested as a new first-line treatment option to replace the standard triple therapy (STT) comprising a proton pump inhibitor (PPI), clarithromycin and amoxicillin, in which eradication proportions have declined to disappointing levels. To conduct a meta-analysis of randomised controlled trials (RCTs) comparing the efficacy of a SEQ regimen with STT for the eradication of H. pylori infection, and to compare the incidence of adverse effects associated with both STT and SEQ H. pylori eradication therapies. We conducted bibliographical searches in electronic databases, and handsearched abstracts from Congresses up to April 2015. We sought randomised controlled trials (RCTs) comparing 10-day SEQ and STT (of at least seven days) for the eradication of H. pylori. Participants were adults and children diagnosed as positive for H. pylori infection and naïve to H. pylori treatment. We used a pre-piloted, tabular summary to collect demographic and medical information of included study participants as well as therapeutic data and information related to the diagnosis and confirmatory tests.We evaluated the difference in intention-to-treat eradication between SEQ and STT regimens across studies, and assessed sources of the heterogeneity of this risk difference (RD) using subgroup analyses.We evaluated the quality of the evidence following Cochrane standards, and summarised it using GRADE methodology. We included 44 RCTs with a total of 12,284 participants (6042 in SEQ and 6242 in STT). The overall analysis showed that SEQ was significantly more effective than STT (82% vs 75% in the intention-to-treat analysis; RD 0.09, 95% confidence interval (CI) 0.06 to 0.11; P STT were greater in Europe (RD 0.16, 95

  15. Modals of Strong Obligation

    Science.gov (United States)

    Matthews-Bresky, R. J. H.

    1977-01-01

    Discusses regularities and peculiarities in the use of the modal verbs of obligation "must,""need" and "should," also of the non-modals "have (got) to" and "need to." Agreements and differences in the use of the verbs are shown, with examples. Use of the various tense-forms is discussed. (IFS/WGA)

  16. Video: Modalities and Methodologies

    Science.gov (United States)

    Hadfield, Mark; Haw, Kaye

    2012-01-01

    In this article, we set out to explore what we describe as the use of video in various modalities. For us, modality is a synthesizing construct that draws together and differentiates between the notion of "video" both as a method and as a methodology. It encompasses the use of the term video as both product and process, and as a data collection…

  17. Advances in Modal Logic

    DEFF Research Database (Denmark)

    Modal logic is a subject with ancient roots in the western logical tradition. Up until the last few generations, it was pursued mainly as a branch of philosophy. But in recent years, the subject has taken new directions with connections to topics in computer science and mathematics. This volume i...... epistemic logic, and the logic of evidence.......Modal logic is a subject with ancient roots in the western logical tradition. Up until the last few generations, it was pursued mainly as a branch of philosophy. But in recent years, the subject has taken new directions with connections to topics in computer science and mathematics. This volume...... is the proceedings of the conference of record in its fi eld, Advances in Modal Logic. Its contributions are state-of-the-art papers. The topics include decidability and complexity results for specifi c modal logics, proof theory of modal logic, logics for reasoning about time and space, provability logic, dynamic...

  18. Parametric modal transition systems

    DEFF Research Database (Denmark)

    Beneš, Nikola; Křetínský, Jan; Larsen, Kim Guldstrand;

    2011-01-01

    Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refin......Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects...... in the refinement process like exclusive, conditional and persistent choices. We introduce a new model called parametric modal transition systems (PMTS) together with a general modal refinement notion that overcome many of the limitations and we investigate the computational complexity of modal refinement checking....

  19. Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations.

    Science.gov (United States)

    Tan, Pui San; Bilger, Marcel; de Lima Lopes, Gilberto; Acharyya, Sanchalika; Haaland, Benjamin

    2017-08-01

    Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed

  20. Successful Treatment of Liver Aspergilloma by Caspofungin Acetate First-Line Therapy in a Non-Immunocompromised Patient

    Directory of Open Access Journals (Sweden)

    Hong-Juan Dong

    2012-09-01

    Full Text Available Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

  1. The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Aronsson, Mattias; Walfridsson, Håkan; Janzon, Magnus

    2014-01-01

    AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model......, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain...... of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost...

  2. Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Wang Ming; Zheng Xiaofeng; Ruan Xiaojiao; Ye Bailiang; Cai Long; Lin Feizhuan; Tu Jinfu

    2014-01-01

    Background What benefits and toxicities patients acquire from the use of bevacizumab combined with first-line chemotherapy remains controversial.This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer (mCRC).Methods Several databases,including PubMed,Embase,and Cochrane Library,were searched up to April 30,2013.Eligible studies were only randomized,controlled trials (RCTs) with a direct comparison between mCRC patients treated with and without bevacizumab.Overall risk ratio (RR),hazard ratio (HR),odds ratio (OR),and 95% confidence intervals (CO were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials.Results Six RCTs,including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group,were included.Overall,the addition of bevacizumab to first-line chemotherapy increased overall response rate (ORR) by 4.5%,prolonged both progression-free survival (PFS) and overall survival (OS),and increased the rate of total Grades 3 or 4 adverse events (G3/4AEs) by 6.9%.Significant differences were found in ORR (RR=1.22 (95% CI 1.01-1.46),P=0.03),PFS (HR=0.60 (95% Cl 0.47-0.77),P <0.0001),OS (HR=0.83 (95% Cl 0.70-0.97),P=0.02),and any G3/4AEs (OR=1.56 (95% Cl 1.29-1.89),P <0.00001).Conclusion Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC,because of conferring a significant improvement in ORR,PFS,and OS,even though it increased adverse events.

  3. Clinical outcome of patients who reduced sunitinib or pazopanib during first-line treatment for advanced kidney cancer.

    Science.gov (United States)

    Iacovelli, Roberto; Cossu Rocca, Maria; Galli, Luca; De Giorgi, Ugo; Sabbatini, Roberto; Santoni, Matteo; Mosca, Alessandra; Fornarini, Giuseppe; Massari, Francesco; Masini, Cristina; Bersanelli, Melissa; Biasco, Elisa; Lolli, Cristian; Guida, Annalisa; Berardi, Rossana; Terrone, Carlo; Pastorino, Alessandro; Ardizzoni, Andrea; Pinto, Carmine; Buti, Sebastiano; Nolè, Franco; Tortora, Giampaolo

    2017-09-01

    To investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who continue at the standard dose. All the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. A total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42-2.29; P<0.001). Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy (P = 0.007). Toxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Effective Selection: A Study of First-Line Supervisor Selection Processes in the Department of Homeland Security

    Science.gov (United States)

    2011-03-01

    survive in a free market economy. Unlike the private sector, the federal government is not concerned about profits and loss and worries less about...all DHS agencies as a strategy to cut down costs associated with implementing best practices for first-line supervisor selection. Additionally, by...U.S. Coast Guard (CG) HSAD U.S. Secret Service (SS) HSBB Immigration and Customs Enforcement (ICE) HSBC Transportation Security Administration (TSA

  5. Tumor characteristics and metastatic sites may predict bevacizumab efficacy in the first-line treatment of metastatic colorectal cancer

    OpenAIRE

    Varol, Umut; Oktay, Esin; YILDIRIM, Mustafa; SURMELI, ZEKI GOKHAN; Dirican, Ahmet; Meydan, Nezih; KARACA, BURCAK; Karabulut, Bulent; Uslu, Ruchan

    2013-01-01

    Colorectal cancer (CRC) is among the most frequently diagnosed cancers and a major cause of cancer-related mortality worldwide. The aim of the present study was to determine whether there was an improvement in the time to disease progression (TTP) in patients with metastatic colorectal cancer (mCRC) treated with first-line bevacizumab plus chemotherapy, according to tumor characteristics and metastatic sites. Tumor characteristics and tumor burden were considered to be predictive markers of t...

  6. First-line trastuzumab plus taxane-based chemotherapy for metastatic breast cancer: cost-minimization analysis.

    Science.gov (United States)

    Nerich, Virginie; Chelly, Jennifer; Montcuquet, Philippe; Chaigneau, Loïc; Villanueva, Cristian; Fiteni, Frédéric; Meneveau, Nathalie; Perrin, Sophie; Voidey, Aline; Monnot, Tess; Pivot, Xavier; Limat, Samuel

    2014-10-01

    To carry out a cost-minimization analysis including a comparison of the costs arising from first-line treatment by trastuzumab plus docetaxel versus trastuzumab plus paclitaxel in patients with metastatic breast cancer. All consecutive patients with human epidermal growth receptor 2-postive metastatic breast cancer who were treated at Besançon University Hospital and Saint Vincent private hospital between 2001 and 2010 by first-line therapy containing trastuzumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization, and healthcare travel. Progression-free survival difference between the two treatments was not significant (p = 0.65). First-line treatment by trastuzumab plus taxane was estimated at approximately €68,000 (p = 0.74). The drug costs represented around 70-75% of the total cost, mainly related to the use of trastuzumab. Our economic analysis shows that although the costs of the two trastuzumab plus taxane regimens are similar, they may contribute to the on-going debate about the availability and use of innovative chemotherapy drugs, in particular in human epidermal growth factor receptor 2-positive metastatic breast cancer with new therapies such as trastuzumab-DM1 and pertuzumab. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. Coherence for Modalities

    CERN Document Server

    Dosen, K

    2008-01-01

    Positive modalities in systems in the vicinity of S4 and S5 are investigated in terms of categorial proof theory. Coherence and maximality results are demonstrated, and connections with mixed distributive laws and Frobenius algebras are exhibited.

  8. Modalities in medieval logic

    OpenAIRE

    2009-01-01

    This dissertation is an exercise in conceptual archeology. Using the tools of contemporary logic we analyse texts in medieval logic and reconstruct their logical theories by creating a formal framework which models them. Our focus is medieval texts which deal with various modalities: the writings on alethic modalities by William of Sherwood, Pseudo-Aquinas, and St. Thomas Aquinas in the 13th century, St. Anselm of Canterbury’s writings on facere and debere in the late 11th century; Lambert of...

  9. {sup 11}C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series

    Energy Technology Data Exchange (ETDEWEB)

    Graziani, Tiziano; Ceci, Francesco; Polverari, Giulia; Lima, Giacomo Maria; Lodi, Filippo; Fanti, Stefano [S. Orsola-Malpighi Hospital, University of Bologna, Service of Nuclear Medicine, Bologna (Italy); Castellucci, Paolo [S. Orsola-Malpighi Hospital, University of Bologna, Service of Nuclear Medicine, Bologna (Italy); Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola-Malpighi, UO Medicina Nucleare, Bologna (Italy); Morganti, Alessio Giuseppe [S. Orsola-Malpighi Hospital, University of Bologna, Department of Radiotherapy, Bologna (Italy); Ardizzoni, Andrea [S. Orsola-Malpighi Hospital, University of Bologna, Department of Oncology, Bologna (Italy); Schiavina, Riccardo [S. Orsola-Malpighi Hospital, University of Bologna, Department of Urology, Bologna (Italy)

    2016-10-15

    To evaluate {sup 11}C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing {sup 11}C-choline PET/CT during BCR. We retrospectively analysed 9,632 {sup 11}C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. Overall, 52.8 % of the {sup 11}C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 - 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive {sup 11}C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 {sup 11}C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans. In a large cohort of patients, the feasibility of {sup 11}C

  10. Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure

    Directory of Open Access Journals (Sweden)

    Chen Mao-Yuan

    2009-09-01

    Full Text Available Abstract Background Tipranavir (TPV is a recently approved nonpeptidic protease inhibitor (PI of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable. Methods To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively, but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score. Results Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007. 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P Conclusion Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.

  11. Virological efficacy with first-line antiretroviral treatment in India: predictors of viral failure and evidence of viral resuppression.

    Science.gov (United States)

    Shet, Anita; Neogi, Ujjwal; Kumarasamy, N; DeCosta, Ayesha; Shastri, Suresh; Rewari, Bharat Bhushan

    2015-11-01

    Combination antiretroviral therapy (ART) has improved in efficacy, durability and tolerability. Virological efficacy studies in India are limited. We determined incidence and predictors of virological failure among patients initiating first-line ART and described virological resuppression after confirmed failure, with the goal of informing national policy. Therapy-naïve patients initiated on first-line ART as per national guidelines were monitored every 3 months for adherence and virological response over 2 years. Genotyping on baseline samples was performed to assess primary drug resistance. Multivariate Cox regression analysis was used to assess predictors of virological failure. Virological failure rate among 599 eligible patients was 10.7 failures per 100 person-years. Cumulative failure incidence was 13.2% in the first year and 16.5% over 2 years. Patients initiated on tenofovir had a significantly lower rate of virological failure than those on stavudine or zidovudine (6.7 vs. 11.9 failures per 100 person-years, P = 0.013). Virological failure was independently associated with age <40 years, mean adherence <95%, non-tenofovir-containing regimens and presence of primary drug resistance. In a subset of 311 patients who were reassessed after treatment failure, 19% (11/58) patients resuppressed their viral load to <400 copies/ml after confirmed virological failure. Our results support the inclusion of tenofovir as first-line ART in resource-limited settings and a role for regular adherence counselling and virological monitoring for enhanced treatment success. Detection of early virological failure should provide an opportunity to augment adherence counselling and repeat viral load testing before therapy switch is considered. © 2015 John Wiley & Sons Ltd.

  12. Gemcitabine and irinotecan as first-line therapy for carcinoma of unknown primary: results of a multicenter phase II trial.

    Directory of Open Access Journals (Sweden)

    Shernan G Holtan

    Full Text Available Metastatic carcinoma of unknown primary (CUP has a very poor prognosis, and no standard first-line therapy currently exists. Here, we report the results of a phase II study utilizing a combination of gemcitabine and irinotecan as first-line therapy. Treatment was with gemcitabine 1000 mg/m(2 and irinotecan 75 mg/m(2 weekly times four on a six week cycle (Cohort I. Due to excessive toxicity, the dose and schedule were modified as follows: gemcitabine 750 mg/m(2 and irinotecan 75 mg/m(2 given weekly times three on a four week cycle (Cohort II. The primary endpoint was the confirmed response rate (CR + PR. Secondary endpoints consisted of adverse events based upon the presence or absence of the UDP glucuronosyltransferase 1 family, polypeptide A1*28 (UGT1A1*28 polymorphism, time to progression, and overall survival. Thirty-one patients were enrolled with a median age of 63 (range: 38-94, and 26 patients were evaluable for efficacy. Significant toxicity was observed in Cohort 1, characterized by 50% (7/14 patients experiencing a grade 4+ adverse event, but not in cohort II. The confirmed response rate including patients from both cohorts was 12% (95% CI: 2-30%, which did not meet the criteria for continued enrollment. Overall median survival was 7.2 months (95% CI: 4.0 to 11.6 for the entire cohort but notably longer in cohort II than in cohort I (9.3 months (95% CI: 4.1 to 12.1 versus 4.0 months (95% CI: 2.2 to 15.6. Gemcitabine and irinotecan is not an active combination when used as first line therapy in patients with metastatic carcinoma of unknown primary. Efforts into developing novel diagnostic and therapeutic approaches remain important for improving the outlook for this heterogeneous group of patients.ClinicalTrials.gov NCT00066781.

  13. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Directory of Open Access Journals (Sweden)

    Awachana Jiamsakul

    2014-08-01

    Full Text Available Introduction: First-line antiretroviral therapy (ART failure often results from the development of resistance-associated mutations (RAMs. Three patterns, including thymidine analogue mutations (TAMs, 69 Insertion (69Ins and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs and may compromise treatment options for second-line ART. Methods: We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M, and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL 2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001. Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81, p=0.001. Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions: Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

  14. Chemotherapy plus bevacizumab versus chemotherapy plus cetuximab as first-line treatment for patients with metastatic colorectal cancer

    Science.gov (United States)

    Bai, Long; Wang, Feng; Li, Zhe-zhen; Ren, Chao; Zhang, Dong-sheng; Zhao, Qi; Lu, Yun-xin; Wang, De-shen; Ju, Huai-qiang; Qiu, Miao-zhen; Wang, Zhi-qiang; Wang, Feng-hua; Xu, Rui-hua

    2016-01-01

    Abstract The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry study where mCRC patients received first-line fluoropyrimidine-based chemotherapy combined with either bevacizumab (188 patients with KRAS wild-type or mutated tumors) or cetuximab (101 patients with KRAS wild-type tumors) between January 2009 and December 2013. The Kaplan–Meier method was used for survival analysis. Cox proportional hazards model was used for estimating the prognostic and predictive values of clinicopathological characteristics. No statistically significant difference was observed between the bevacizumab and cetuximab groups in terms of median progression-free survival (PFS) (10.6 vs 8.7 months, P = 0.317), median overall survival (OS) (27.7 vs 28.3 months, P = 0.525), or overall response rate (43.1% vs 53.5%, P = 0.108). For the subset of patients with peritoneal dissemination, bevacizumab-based triplet appears to be superior to cetuximab-based triplet as measured by PFS (9.6 vs 6.1 months) and OS (26.3 vs 12.7 months), but not for patients without peritoneal dissemination (PFS, 10.6 vs 9.1 months; OS, 27.9 vs 30.7 months) (all unadjusted and adjusted interaction P < 0.05). Our study suggests that bevacizumab- or cetuximab-based regimens have similar effectiveness as first-line treatment of mCRC in Chinese population. Patients with peritoneal dissemination were likely to gain more benefit from bevacizumab than cetuximab treatment. Future prospective studies are required to further confirm these results. PMID:28002313

  15. The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy.

    Science.gov (United States)

    Faloppi, Luca; Del Prete, Michela; Casadei Gardini, Andrea; Santini, Daniele; Silvestris, Nicola; Bianconi, Maristella; Giampieri, Riccardo; Valgiusti, Martina; Brunetti, Oronzo; Bittoni, Alessandro; Andrikou, Kalliopi; Lai, Eleonora; Dessì, Alessandra; Cascinu, Stefano; Scartozzi, Mario

    2016-04-11

    LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37-0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54-1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33-0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27-0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy.

  16. Toward predicate approaches to modality

    CERN Document Server

    Stern, Johannes

    2016-01-01

    In this volume, the author investigates and argues for, a particular answer to the question: What is the right way to logically analyze modalities from natural language within formal languages? The answer is: by formalizing modal expressions in terms of predicates. But, as in the case of truth, the most intuitive modal principles lead to paradox once the modal notions are conceived as predicates. The book discusses the philosophical interpretation of these modal paradoxes and argues that any satisfactory approach to modality will have to face the paradoxes independently of the grammatical category of the modal notion. By systematizing modal principles with respect to their joint consistency and inconsistency, Stern provides an overview of the options and limitations of the predicate approach to modality that may serve as a useful starting point for future work on predicate approaches to modality. Stern also develops a general strategy for constructing philosophically attractive theories of modal notions conce...

  17. [Bevacizumab as first-line therapy in metastatic renal cell carcinoma: Progression-free survival for 3 years].

    Science.gov (United States)

    Pichler, R; Horninger, W; Aigner, F; Heidegger, I

    2016-03-01

    We report the case of a 72-year-old woman who was diagnosed in 2006 with renal cell cancer (RCC) and had undergone consecutive tumor nephrectomy (clear-cell RCC, Fuhrmann grade II, stage pT3a, R0). Over the years, the patient underwent several surgical and radiological interventions due to various metastatic lesions. This case report describes the 3-year progression-free survival in a patient who underwent first-line therapy with the monoclonal antibody bevacizumab. Except for hypertension, the patient does not suffer currently from any other side effects of bevacizumab therapy.

  18. Cost and resource utilization associated with fluconazole as first-line therapy for invasive candidiasis: a retrospective database analysis.

    Science.gov (United States)

    Craver, Christopher W; Tarallo, Miriam; Roberts, Craig S; Blanchette, Christopher M; Ernst, Frank R

    2010-12-01

    Fluconazole is a standard first-line therapy for candidemia/invasive candidiasis (C/IC), based on its efficacy, safety profile, and comparatively low acquisition cost. However, little is known about the total costs associated with fluconazole treatment for this indication, particularly in cases of clinical failure. The aim of this study was to examine overall costs, resource use, and treatment outcomes associated with fluconazole as first-line therapy for invasive Candida infections in the United States. A retrospective analysis of data from a US hospital-based (>500 hospitals), service-level database was performed. All patients aged >16 years with primary or secondary International Classification of Diseases, Ninth Revision, Clinical Modification codes for IC or septicemia, receiving intravenous fluconazole treatment, and discharged between October 1, 2004 and September 30, 2005 were selected. Costs and resource use were calculated from the start of antifungal therapy until discharge. Two groups were analyzed: patients who received fluconazole only and those who required a second-line antifungal. Separate analyses for the survivor subpopulations were also conducted. A total of 7170 patients met the inclusion criteria; 21.2% required an additional antifungal agent. Overall mortality was 27.1%, and total mean treatment cost for all patients was $44,482 (in 2005 US dollars). Patients treated with fluconazole alone incurred mean costs of $36,319. Mean hospital and intensive care unit stays in the fluconazole monotherapy group were 17.9 days and 7.1 days, respectively. Patients requiring additional therapy had a mortality rate of 34.5% and a mean treatment cost of $76,329; in this group, the mean hospital and intensive care unit stays were 31.7 days and 14.8 days, respectively. The overall resource use associated with fluconazole as first-line treatment for C/IC was high, especially in patients who required additional antifungal therapy. Future studies should examine

  19. First-line eradication of Helicobacter pylori:Are the standard triple therapies obsolete? A different perspective

    Institute of Scientific and Technical Information of China (English)

    Gyrgy; Miklós; Buzás

    2010-01-01

    Studies concerning the eradication of Helicobacter pylori have resulted in a proliferation of meta-analyses. To date, there are 303 meta-analyses cited in PubMed, 113 dealing with the therapy of the infection. A chronological analysis of the results of meta-analyses performed between 1998 and 2010 shows that first-line standard triple therapies achieved eradication rates on an intention-to-treat basis of around 80%; prolonging treatment to 14, but not 10 d should improve the results. The proton pump inhibit...

  20. [A negative first-line work-up of Raynaud's phenomenon: And what if it were cancer?].

    Science.gov (United States)

    Auboire, L; Landy, S; Perrot, J-Y; Maïza, D; Le Hello, C

    2010-02-01

    Raynaud's phenomenon is a transient paroxysmal vasomotor phenomenon affecting the extremities including manifestations of ischemia. It is a common phenomenon in the general population. In a routine clinical situation, the first step is to differentiate Raynaud's disease from a secondary Raynaud's phenomenon, the latter requiring complementary investigations. We report here the case of an 80-year-old woman who presented a secondary Raynaud's phenomenon. First-line investigations remained negative. A mammography was performed and revealed breast cancer. Raynaud's phenomenon disappeared after treatment of the breast carcinoma and did not recur during the 2-year follow-up.

  1. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence

  2. First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis

    NARCIS (Netherlands)

    B. Kasenda (Benjamin); A.J.M. Ferreri (Andrés J.M.); E. Marturano; D. Forst; J.E.C. Bromberg (Jacolien); H. Ghesquieres; C. Ferlay; J-Y. Blay (Jean Yves); K. Hoang-Xuan (Khê); E.J. Pulczynski; A. Fosså; Y. Okoshi; S. Chiba; K. Fritsch (Kristina); A. Omuro; B.P. O'Neill; O. Bairey; S. Schandelmaier; V. Gloy; N. Bhatnagar; S. Haug; S. Rahner; T.T. Batchelor (Tracy); G. Illerhaus (Gerald); M. Brie

    2015-01-01

    textabstractBackground: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients. Patients and methods: A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta

  3. The Difference Between Modal Verbs in Deontic and Epistemic Modality

    Directory of Open Access Journals (Sweden)

    Menik Winiharti

    2012-10-01

    Full Text Available Modality is always interesting to discuss. Understanding it is crucial for both language teachers and learners. This essay discusses the concept of modality, its types and uses. It has a goal to find the difference between deontic and epistemic modality that is indicated by their modal verbs. It also provides the readers a better understanding of modality, particularly of its types and uses. The result of the analysis shows that in general, deontic modality indicates obligation and permission, while epistemic modality expresses possibility and prediction. However, the difference between deontic and epistemic modality is not a clear cut, since one single modal verb can express both types, and one single proposition can be expressed by more than one modal verb.  

  4. Refinement Modal Logic

    CERN Document Server

    Bozzelli, Laura; French, Tim; Hales, James; Pinchinat, Sophie

    2012-01-01

    In this paper we present refinement modal logic. A refinement is like a bisimulation, except that from the three relational requirements only 'atoms' and 'back' need to be satisfied. Our logic contains a new operator 'forall' in additional to the standard modalities 'Box' for each agent. The operator 'forall' acts as a quantifier over the set of all refinements of a given model. We call it the refinement operator. As a variation on a bisimulation quantifier, it can be seen as a refinement quantifier over a variable not occurring in the formula bound by the operator. The logic combines the simplicity of multi-agent modal logic with some powers of monadic second order quantification. We present a sound and complete axiomatization of multiagent refinement modal logic. We also present an extension of the logic to the modal mu-calculus, and an axiomatization for the single-agent version of this logic. Examples and applications are also discussed: to software verification and design (the set of agents can also be s...

  5. Intratympanic steroid injection as a first-line therapy in uremia patients with sudden sensorineural hearing loss.

    Science.gov (United States)

    Tsai, Hsun-Tien; Hsueh, Naiwei; Huang, Chih-Ming; Lin, Hung-Ching

    2015-08-01

    ITSI as a first-line therapy in uremia patients with SSNHL offers a valid and safe treatment compared with intravenous systemic steroid treatment. A specific pathophysiology caused by possible sodium pump paralysis may be explained for uremia patients with SSNHL. To compare the efficacy of intratympanic steroid injection (ITSI) with that of systemic intravenous steroids as a first-line therapy in uremia patients with sudden sensorineural hearing loss (SSNHL). A total of 23 consecutive uremia patients with SSNHL were enrolled in this study. Patients were divided into two groups: the ITSI group (n = 15) and the non-ITSI group (n = 8), in which patients received intravenous systemic steroid treatment. The two groups were homogeneous in all respects. The hearing improvement and relative gain were statistically significant between the two groups. The value of hearing gain (ΔPTA = PTA pre - PTA post) in the ITSI group and the non-ITSI group was 24.6 ± 16.4dB and 8.4 ± 19.3dB. The value of relative gain (ΔPTA/PTApre) in the ITIS group and the non-ITSI group was 31.1 ± 22% and 9.4 ± 20.5%. In the ITSI group, 11 patients (73.3%) exhibited hearing recovery (ΔPTA > 10 dB).

  6. Ovarian cancer: advances in first-line treatment strategies with a particular focus on anti-angiogenic agents.

    Science.gov (United States)

    Collinson, Fiona J; Seligmann, Jenny; Perren, Timothy J

    2012-12-01

    Ovarian cancer is an important health concern worldwide. The majority of patients present with advanced disease, and despite initial chemosensitivity, most relapse and die from their disease. Better therapeutic options are urgently required. Maximal surgical debulking in combination with platinum/taxane chemotherapy has been the standard of care in advanced ovarian cancer since the mid-1990s. Trials investigating the addition of a third chemotherapeutic agent have disappointingly failed to demonstrate benefit. Intra-peritoneal therapy demonstrated improvements in outcomes in some trials, but at the cost of increased toxicity and inconvenience. Encouragingly, prospective data has now demonstrated benefits with bevacizumab in both the first-line and relapsed settings; however, interpretation is complex, particularly considering recent data demonstrating non-inferiority of neo-adjuvant chemotherapy with delayed primary surgery, and other data demonstrating a substantial improvement in outcome as a result of first-line paclitaxel dose fractionation. This article reviews the recent advances in ovarian cancer treatment and discusses current management and key areas for future research.

  7. Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen.

    Science.gov (United States)

    Sachanas, Sotirios; Pangalis, Gerassimos A; Vassilakopoulos, Theodoros P; Korkolopoulou, Penelope; Kontopidou, Flora N; Athanasoulia, Maria; Yiakoumis, Xanthi; Kalpadakis, Christina; Georgiou, Georgios; Masouridis, Stavroula; Moschogiannis, Maria; Tsirkinidis, Pantelis; Pappis, Vassiliki; Kokoris, Styliani I; Siakantaris, Marina P; Panayiotidis, Panayiotis; Angelopoulou, Maria K

    2011-03-01

    The optimal treatment approach for patients with mantle cell lymphoma (MCL) is not well defined. Intensive therapeutic regimens result in high response rates and prolonged progression-free survival but at the expense of significant toxicity. We report here our results of the administration of rituximab plus chlorambucil (R-Chl) as first line treatment in patients with MCL. Twenty consecutively diagnosed patients were treated with this combination in which an induction and a maintenance arm were included. During induction, rituximab was administered at a dose of 375 mg/m(2) on day 1, while chlorambucil was given afterward at a dose of 10 mg/day for 10 consecutive days for eight cycles and then as a single agent for an additional four cycles. Maintenance consisted of rituximab administration every 2 months for 1 year. Most patients had indolent disease features such as a low mantle-cell international prognostic index (MIPI) score. The overall response rate was 95% (90% CR, 5% PR). Among patients in CR, 78% presented a molecular remission. The 3-year progression-free survival was 89%. There were no serious side effects. These results show that the R-Chl combination could be an effective therapeutic option as first line treatment in MCL, especially for patients with indolent disease characteristics.

  8. Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery.

    Science.gov (United States)

    Cappabianca, Giangiuseppe; Mariscalco, Giovanni; Biancari, Fausto; Maselli, Daniele; Papesso, Francesca; Cottini, Marzia; Crosta, Sandro; Banescu, Simona; Ahmed, Aamer B; Beghi, Cesare

    2016-01-06

    Bleeding after cardiac surgery requiring surgical reexploration and blood component transfusion is associated with increased morbidity and mortality. Although prothrombin complex concentrate (PCC) has been used satisfactorily in bleeding disorders, studies on its efficacy and safety after cardiopulmonary bypass are limited. Between January 2005 and December 2013, 3454 consecutive cardiac surgery patients were included in an observational study aimed at investigating the efficacy and safety of PCC as first-line coagulopathy treatment as a replacement for fresh frozen plasma (FFP). Starting in January 2012, PCC was introduced as solely first-line treatment for bleeding following cardiac surgery. After one-to-one propensity score-matched analysis, 225 pairs of patients receiving PCC (median dose 1500 IU) and FFP (median dose 2 U) were included. The use of PCC was associated with significantly decreased 24-h post-operative blood loss (836 ± 1226 vs. 935 ± 583 ml, p surgery setting, the use of PCC compared with FFP was associated with decreased post-operative blood loss and RBC transfusion requirements. However, PCC administration may be associated with a higher risk of post-operative AKI.

  9. Efficacy of rabbit antithymocyte globulin as first-line treatment of severe aplastic anemia: an Asian multicenter retrospective study.

    Science.gov (United States)

    Chuncharunee, Suporn; Wong, Raymond; Rojnuckarin, Ponlapat; Chang, Cheng-Shyong; Chang, Kian Meng; Lu, Meng-Yao; Hwang, Wen-Li; Koh, Liang Piu; Chen, Tsai-Yun; Leung, Anskar Yh; Norasetthada, Lalita; Wang, Shih-Chung; Chang, Ming-Chih; Wu, Kang-Hsi; Issaragrisil, Surapol

    2016-10-01

    Due to the unavailability of horse antithymocyte globulin (ATG) in many markets worldwide, patients with severe aplastic anemia (SAA) are limited to the use of rabbit ATG. We aimed to analyze hematologic response and overall survival (OS) of Asian patients treated with rabbit ATG as first-line therapy of SAA. We retrospectively reviewed the medical records of 97 consecutive patients who received rabbit ATG as first-line treatment of SAA from 2006 to 2012 at centers in four Asian countries. The primary endpoint was 6- and 12-month overall response rates (ORR) for patients receiving rabbit ATG within the recommended dose range (2.5-3.75 mg/kg/day). Secondary endpoints included ORR in patients receiving any dose of rabbit ATG and 2-year OS. For patients who received rabbit ATG within the recommended dose range, 6- and 12-month ORRs were 17.4 and 63.6 %, respectively. For patients who received any dose of rabbit ATG, 6- and 12-month ORRs were 24.3 and 68.6 %, respectively. The 2-year OS rate was 86.3 %. Rabbit ATG is effective for treatment of SAA in Asian patients. The 12-month ORR and 2-year OS with rabbit ATG were comparable to historical results obtained with horse ATG.

  10. Metabolic syndrome in patients on first-line antiretroviral therapy containing zidovudine or tenofovir in rural Lesotho, Southern Africa.

    Science.gov (United States)

    Labhardt, Niklaus Daniel; Müller, Urs Franz; Ringera, Isaac; Ehmer, Jochen; Motlatsi, Mokete M; Pfeiffer, Karolin; Hobbins, Michael A; Muhairwe, Josephine A; Muser, Juergen; Hatz, Christoph

    2017-06-01

    To assess the prevalence of metabolic syndrome (MetS) among patients in rural Lesotho who are taking first-line antiretroviral therapy (ART) containing either zidovudine or tenofovir disoproxil. Cross-sectional survey in 10 facilities in Lesotho among adult (≥16 years) patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART for ≥6 months. MetS was defined according to the International Diabetes Federation criteria. Among 1166 patients (65.8% female), 22.2% (95% CI: 19.3-25.3) of women and 6.3% (4.1-9.1) of men met the IDF definition of MetS (P < 0.001). In both sexes, there was no significant difference in MetS prevalence between NNRTIs. However, in women taking zidovudine as nucleoside reverse transcriptase inhibitor (NRTI), MetS prevalence was 27.9%, vs. 18.8% in those taking tenofovir. In the multivariate logistic regression allowing for socio-demographic and clinical covariates, ART containing zidovudine was associated with MetS in women (aOR 2.17 (1.46-3.22), P < 0.001) but not in men. In this study, taking ART containing zidovudine instead of tenofovir disoproxil was an independent predictor of MetS in women but not in men. This finding endorses WHO's recommendation of tenofovir as preferred NRTI. © 2017 John Wiley & Sons Ltd.

  11. First-line treatment of EGFR-mutated nonsmall cell lung cancer: critical review on study methodology

    Directory of Open Access Journals (Sweden)

    Martin Sebastian

    2014-03-01

    Full Text Available Recent advances in understanding the mechanisms of nonsmall cell lung cancer (NSCLC has led to the development of targeted treatments, including the reversible epidermal growth factor receptor (EGFR tyrosine kinase inhibitors gefitinib and erlotinib, and the irreversible ErbB family blocker afatinib. Several important activating EGFR mutations have now been identified, which correlate strongly with response to treatment with these agents. Multiple randomised controlled trials have confirmed the association between the presence of activating EGFR mutations and objective response to gefitinib, erlotinib and afatinib, thus demonstrating their superiority over platinum-based chemotherapy as first-line treatment for NSCLC patients with EGFR mutation-positive tumours, and resulting in approval of these agents for use in this setting. It can be tempting to compare outcome data across multiple clinical trials and agents; however, substantial differences in methodology between studies, including investigator versus independent assessment and differences in patient eligibility, makes such comparisons fraught with difficulty. This critical review provides an overview of the evolution of the methodology used in eight phase III trials investigating first-line targeted treatment of NSCLC, identifies key differences in methodology and reporting, and critically assesses how these differences should be taken into account when interpreting the findings from such trials.

  12. Evaluation of Outcome and Tolerability of Combination Chemotherapy with Capecitabine and Oxaliplatin as First Line Therapy in Advanced Gastric Cancer

    Science.gov (United States)

    Mashhadi, Mohammad Ali; Sepehri, Zahra; Bakhshipour, Ali Reza; Zivari, Ali; Danesh, Hossein Ali; Metanat, Hasan Ali; Karimkoshteh, Azra; Hashemi, Seyed Mehdi; Rahimi, Hossein; Kiani, Zohre

    2016-01-01

    Background: Combination chemotherapy is accepted as a high efficacy treatment for gastric cancer, whereas choice of standard treatment is unclear. Multiple chemotherapeutic regimens have been used to achieve higher efficacy and lower toxicity. This study was designed to evaluate the treatment results of advanced gastric cancer with Capecitabine and Oxaliplatin regimen. Subjects and Methods : All cases with documented gastric adenocarcinoma and advanced disease were candidates for receiving Xelox regimen (Capecitabine – 750 mg/m2/twice daily/ 1-14 days and Oxaliplatin 125 mg/m2 in 1st day). Results: Twenty five cases with advanced gastric cancer entered in study while 24 cases continued treatment protocol and were evaluated. Mean age was 59.5 ± 12.1 years (range: 20-75), male and female cases were 66.7% and 33.3%, respectively. All cases received at least four cycles of Xelox regimen. Overall response rate was 74.99% with 29.16% complete response. Overall survival rate was 13 ± 0.53 months and DFS (disease-free survival) was 6 ± 1.09 months. Extremities neuropathy (62.5%), headache (45.8%) and muscle cramps (29.2%) were the most common complains. Haematological changes were rare and 16.7% of cases had mild cytopenia. Treatment related death was not observed. Conclusion: Xelox regimen is a safe and highly effective first line treatment for gastric cancer; however, considering it as first line therapy needs larger studies. PMID:27928475

  13. A modal nonmonotonic logic

    Institute of Scientific and Technical Information of China (English)

    林作铨

    1996-01-01

    A modal nonmonotonic logic is presented based on an experiential modal semantics on typicality and exception.The syntactic and semantics of modal nonmonotonic logic are provided,and the completeness theorem and the theorems relating it to major nonmonotonic logics are proved.It directly formalizes the intuition of nonmonotonic reasoning.Among other things,it provides us a first-order extension of default logic and autoepistemic logic,and simultaneously has the capability of circumscription to infer universal statement.It has important applications in logic programming and deductive data base.As a result,it provides a uniform basis for various nonmonotonic logics,from which the correspondent relationship among major nonmonotonic logics can coincide.

  14. Dominant modal decomposition method

    Science.gov (United States)

    Dombovari, Zoltan

    2017-03-01

    The paper deals with the automatic decomposition of experimental frequency response functions (FRF's) of mechanical structures. The decomposition of FRF's is based on the Green function representation of free vibratory systems. After the determination of the impulse dynamic subspace, the system matrix is formulated and the poles are calculated directly. By means of the corresponding eigenvectors, the contribution of each element of the impulse dynamic subspace is determined and the sufficient decomposition of the corresponding FRF is carried out. With the presented dominant modal decomposition (DMD) method, the mode shapes, the modal participation vectors and the modal scaling factors are identified using the decomposed FRF's. Analytical example is presented along with experimental case studies taken from machine tool industry.

  15. Teaching German Modal Particles.

    Science.gov (United States)

    Rosler, Dietmar

    1982-01-01

    Believes modern linguistics has done little to explore German modal particles because by focusing on sentences as the basic category for linguistic thinking these words did not seem to matter. Describes model which gives students experience with these particles in meaningful communication. (Author/BK)

  16. Tense, aspect, and modality

    NARCIS (Netherlands)

    Pfau, R.; Steinbach, M.; Woll, B.; Pfau, R.; Steinbach, M.; Woll, B.

    2012-01-01

    Cross-linguistically, the grammatical categories tense, aspect, and modality - when they are overtly expressed - are generally realized by free morphemes (such as adverbials and auxiliaries) or by bound inflectional markers. The discussion in this chapter will make clear that this generalization als

  17. Modalities in medieval logic

    NARCIS (Netherlands)

    Uckelman, S.L.

    2009-01-01

    This dissertation is an exercise in conceptual archeology. Using the tools of contemporary logic we analyse texts in medieval logic and reconstruct their logical theories by creating a formal framework which models them. Our focus is medieval texts which deal with various modalities: the writings on

  18. Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes

    Science.gov (United States)

    Fares, Hassan; DiNicolantonio, James J; O'Keefe, James H; Lavie, Carl J

    2016-01-01

    Objectives Hypertension is well established as a major risk factor for cardiovascular disease. Although there is undeniable evidence to support the beneficial effects of antihypertensive therapy on morbidity and mortality, adequate blood pressure management still remains suboptimal. Research into the treatment of hypertension has produced a multitude of drug classes with different efficacy profiles. These agents include β-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers. One of the oldest groups of antihypertensives, the calcium channel blockers are a heterogeneous group of medications. Methods This review paper will focus on amlodipine, a dihydropyridine calcium channel blockers, which has been widely used for 2 decades. Results Amlodipine has good efficacy and safety, in addition to strong evidence from large randomised controlled trials for cardiovascular event reduction. Conclusions Amlodipine should be considered a first-line antihypertensive agent.

  19. Managerial competencies among first-line newsroom managers at small to medium-sized mainstream media enterprises in South Africa

    Directory of Open Access Journals (Sweden)

    Elanie Steyn

    2014-06-01

    Full Text Available Changes in the South African media and management environment have had distinct influences on especially small to medium-sized mainstream media enterprises (media SMEs which often have to compete with bigger media organisations for the same news stories. Moreover, these media organisations are commonly faced with unique challenges related to human and other resources. This situation adds to the importance of effective and efficient management practices at these media sites. The management practices of first-line news managers in media SMEs are qualitatively and quantitatively evaluated in this paper by considering six managerial competencies found in general management theory. These competencies relate to communication, planning and administration, teamwork; strategic action, global awareness and self-management.

  20. Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer

    DEFF Research Database (Denmark)

    Klintman, Marie; Würtz, Sidse Ørnbjerg; Christensen, Ib Jarle;

    2010-01-01

    In a previous study from our laboratory, high tumor levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) have been associated with an adverse response to chemotherapy in metastatic breast cancer suggesting that TIMP-1, which is known to inhibit apoptosis, may be a new predictive marker...... in this disease. The purpose of this study was to investigate the association between TIMP-1 and objective response to chemotherapy in an independent patient population consisting of patients with metastatic breast cancer from Sweden and Denmark. TIMP-1 was measured using ELISA in 162 primary tumor extracts from...... patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0.97-2.62, P = 0...

  1. Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Noemí Reguart

    2010-06-01

    Full Text Available Noemí Reguart1, Andrés Felipe Cardona2, Rafael Rosell31Medical Oncology Service, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain; 2Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, D.C., Colombia; 3Medical Oncology Service, Catalan Institute of Oncology, ICO, Hospital Germans Trias i Pujol, Badalona, Barcelona, SpainAbstract: Erlotinib hydrochloride (Tarceva® is a member of a class of small molecule inhibitors that targets the tyrosine kinase domain of the epidermal growth factor receptor (EGFR, with anti-tumor activity in preclinical models. Erlotinib represents a new-generation of agents known as “targeted therapies” designed to act upon cancer cells by interfering with aberrant specific activated pathways needed for tumor growth, angiogenesis and cell survival. Since its approval in November 2004 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC after the failure of at least one prior chemotherapy regimen and with a view to improving patients’ outcomes and prevent symptoms, the scientific community has evaluated the potential role of erlotinib in other scenarios such as in maintenance therapy and, in first-line setting for a selected population based on biological markers of response such as mutations of the EGFR. The convenient once-a-day pill administration and the good toxicity profile of erlotinib make it a reasonable candidate for testing in this context. This report provides a review of the role of erlotinib therapy in advanced NSCLC. It summarizes current data and perspectives of erlotinib in upfront treatment and maintenance for advanced NSCLC as well as looking at candidate biomarkers of response to these new targeted-agents.Keywords: erlotinib, tyrosine kinase inhibitors, first line, maintenance, non-small-cell lung cancer

  2. Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis.

    Science.gov (United States)

    Zhu, Lucheng; Liu, Jihong; Ma, Shenglin

    2016-10-01

    Fluoropyrimidine-based regimens are the most common treatments in advanced gastric cancer. We used a Bayesian network meta-analysis to identify the optimal fluoropyrimidine-based chemotherapy by comparing their relative efficacy and safety. We systematically searched databases and extracted data from randomized controlled trials, which compared fluoropyrimidine-based regimens as first-line treatment in AGC. The main outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). A total of 12 RCTs of 4026 patients were included in our network meta-analysis. Pooled analysis showed S-1 and capecitabine had a significant OS benefit over 5-Fu, with hazard ratios of 0.90 (95%CI = 0.81-0.99) and 0.88 (95%CI = 0.80-0.96), respectively. The result also exhibited a trend that S-1 and capecitabine prolonged PFS in contrast to 5-Fu, with hazard ratios of 0.84 (95%CI = 0.66-1.02) and 0.84 (95%CI = 0.65-1.03), respectively. Additionally, all the three fluoropyrimidine-based regimens were similar in terms of ORR and grade 3 or 4 AEs. Compared with regimens based on 5-Fu, regimens based on S-1 or capecitabine demonstrated a significant OS improvement without compromise of AEs as first-line treatment in AGC in Asian population. S-1 and capecitabine can be interchangeable according their different emphasis on AEs.

  3. First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Gupta N

    2013-12-01

    Full Text Available Neha Gupta, Hassan Hatoum, Grace K DyDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USAAbstract: Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007 is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel. A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.Keywords: ABI-007, Abraxane, nab

  4. First-Line Use of Core Needle Biopsy for High-Yield Preliminary Diagnosis of Thyroid Nodules.

    Science.gov (United States)

    Kim, H C; Kim, Y J; Han, H Y; Yi, J M; Baek, J H; Park, S Y; Seo, J Y; Kim, K W

    2017-02-01

    Although core needle biopsy was introduced as a diagnostic alternative to fine-needle aspiration, the utility and safety of core needle biopsy for thyroid nodules in a large population has yet to be studied comprehensively. We evaluate core needle biopsy yields on a large-scale basis to investigate its potential in the preliminary diagnosis of thyroid nodules. Between March 2005 and December 2013, 2448 initially detected thyroid nodules from 2120 consecutive patients who underwent core needle biopsy were retrospectively evaluated. Of these, 72 thyroid nodules from 63 patients were excluded due to prior fine-needle aspiration attempts. The inconclusive and conclusive result rates, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and unnecessary surgery rate of core needle biopsy were evaluated. With core needle biopsy as the first-line method, the inconclusive result rate was 11.9% (283/2376) and the conclusive result rate was 88.1% (2093/2376). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of core needle biopsy for the diagnosis of malignancy were 96.7% (1160/1200), 89.7% (347/387), 100% (813/813), 100% (347/347), and 95.3% (813/853), respectively. There were no major complications and 12 minor complications. We have demonstrated that first-line use of core needle biopsy may well improve diagnostic accuracy in thyroid nodules, reducing inconclusive or false-negative results and unnecessary operations. Such benefits underscore the promising role of core needle biopsy in managing thyroid nodules and optimizing related surgical decision-making. © 2017 by American Journal of Neuroradiology.

  5. Success rates of first-line antibiotics for culture-negative sub-acute and chronic septic arthritis.

    Science.gov (United States)

    Chuckpaiwong, Bavornrit; Phoompoung, Saravut

    2014-09-01

    A combination of surgical and medical treatment is normally required for patients with septic arthritis. Antibiotics selected for use on these patients are normally based on tissue culture results. However, in sub-acute and chronic septic arthritis cases, the results of the culture are usually negative as a result of prior treatment. The present study will investigate the incidence of culture-negative septic arthritis and the outcomes based on the use of first-line drug antibiotics for the treatment of sub-acute and chronic septic arthritis. For the present study, the authors retrospectively reviewed medical records of surgically treated septic arthritis cases over the past 10 years at Siriraj Hospital. The patient culture results, the antibiotics used, and the results of treatment were all recorded and analyzed. One hundredfifty-three septic arthritis patients were reviewed. Sixty-two patients were classified as having been diagnosed with either sub-acute or chronic septic arthritis. Thirty-six of 62 patients (58.1%) had a negative culture result. In the culture-positive patients, 42.3% had Streptococcus, 26.9% had Staphylococcus aureus, 11.5% had other gram positive bacteria, 15.4% had gram-negative bacteria, and 3.8% had tuberculus infection. In the culture-negative sub-acute and chronic group (36 of 62), 23 patients received Cefazolin, nine patients received Cloxacillin, and four patients received Clindamycin. Successful results were 69.9%, 66.7% and 75%, respectively. The present study reflects that the incidence ofculture-negative, sub-acute and chronic septic arthritis is approximately 58.1%. The first-line class of antibiotics remains the appropriate antibiotic choice for these patients because they are still effective for treatment of septic arthritis in up to 70% of all cases.

  6. Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women: A prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Sujata Kar

    2012-01-01

    Full Text Available Objective: To compare Letrozole (5 mg and clomiphene citrate (100 mg as first line ovulation induction drug in infertile PCOS women. Study Design: Prospective Randomised trial. Setting: A Tertiary level infertility centre. Patients: 103 infertile PCOS women Intervention(S: Treatment naοve infertile PCOS women were randomised to treatment with 5 mg letrozole (51 patients or 100 mg clomiphene citrate (52 patients daily starting day 2 to day 6 of menstrual cycle. Timed intercourse or Intra Uterine Insemination (IUI was advised 24 to 36 hours after Human Chorionic Gonadotropin (HCG injection. Main Outcome Measures: Ovulation rate, mono or multi follicular rate, days to ovulation, endometrial thickness, serum progesterone, serum estrogen, pregnancy rate, miscarriage rate. Results: The mean age, Body Mass Index (BMI, duration of infertility in both Clomiphene Citrate (CC and Letrozole groups were similar.Ovulation rate was 73.08% in letrozole group and 60.78% in CC, which was not statistically significant (P=0.398. There was no statistically significant difference between Endometrial thickness (CC 7.61 ±1.96, Let 7.65 ± 2.10, Sr E 2 on day of HCG (CC 178.3 ± 94.15, Let 162.09 ± 73.24, Days to ovulation (CC 14.2 ± 3.41; Let 13.13 ± 2.99 and Sr P 4 on D 21 (CC 10.58 ± 6.65; Let 11.86 ± 6.51. Monofolliculo genesis (CC 54.84, Let 79.49 %, P=0.027 and Pregnancy rate (CC 7.84%, Let 21.56% P=0.0125 were statistically significantly higher in letrozole group. Conclusion: Our study shows that letrozole has excellent pregnancy rates compared to clomiphene citrate. Letrozole should be considered at par with clomiphene citrate as first line drug for ovulation induction in infertile PCOS women.

  7. Point-Counterpoint: Large Multiplex PCR Panels Should Be First-Line Tests for Detection of Respiratory and Intestinal Pathogens.

    Science.gov (United States)

    Schreckenberger, Paul C; McAdam, Alexander J

    2015-10-01

    The first FDA-approved multiplex PCR panel for a large number of respiratory pathogens was introduced in 2008. Since then, other PCR panels for detection of several respiratory and gastrointestinal pathogens have been approved by the FDA and are commercially available, and more such panels are likely to become available. These assays detect 12 to 20 pathogens, and some include pathogens that typically cause different manifestations of infection, although they infect the same organ system. Some of these tests are labor-intensive, while others require little labor, and all of them are expensive, both for the laboratory and for the patient or insurer. They include a bundle of tests with limited or no options for selecting which tests will be performed. Laboratories and hospitals have adopted different strategies for offering these assays. Some have implemented strategies to limit the use of the tests, such as limiting the frequency with which patients can be tested, restricting testing to specific groups of patients (e.g., immunocompromised patients), or providing education to encourage the use of less expensive tests before using large multiplex panels. Others have offered these assays without limiting their use, either relying on the ordering provider to exercise good judgment or because such assays are thought to be appropriate for first-line diagnostic testing. In this Point-Counterpoint, Paul Schreckenberger of Loyola University Medical Center explains why his laboratory offers these assays without restriction. Alex McAdam of Boston's Children Hospital explains the concerns about the use of these assays as first-line tests and why some limitations on their use might be appropriate. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Impact of TP53 Mutations on Outcome in EGFR-Mutated Patients Treated with First-Line Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Canale, Matteo; Petracci, Elisabetta; Delmonte, Angelo; Chiadini, Elisa; Dazzi, Claudio; Papi, Maximilian; Capelli, Laura; Casanova, Claudia; De Luigi, Nicoletta; Mariotti, Marita; Gamboni, Alessandro; Chiari, Rita; Bennati, Chiara; Calistri, Daniele; Ludovini, Vienna; Crinò, Lucio; Amadori, Dino; Ulivi, Paola

    2016-10-25

    Purpose: To analyze the impact of TP53 mutations on response to first-line tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC).Experimental Design: 136 EGFR-mutated NSCLC patients receiving first-line TKIs were analyzed. TP53 mutations were evaluated in 123 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).Results:TP53 mutations were observed in 37 (30.1%), 10 (27.0%), 6 (16.2%), 9 (24.3%), and 12 (32.4%) patients in exons 5, 6, 7, and 8, respectively. DCR was 70% in TP53-mutated patients compared with 88% in TP53-wild type (wt) patients [relative risk, RR, of disease progression: 3.17 (95% CI, 1.21-8.48), P = 0.019]. In particular, a 42% DCR was observed in patients with TP53 exon 8 mutation versus 87% in exon 8 wt patients [RR of disease progression 9.6 (2.71-36.63), P TP53 exon 8 mutations compared with others (4.2 vs. 12.5, P = 0.058, and 16.2 vs. 32.3, P = 0.114, respectively); these differences became significant in the subgroup with EGFR exon 19 deletion (4.2 vs. 16.8, P TP53 mutations, especially exon 8 mutations, reduce responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, mainly those carrying exon 19 deletions. Clin Cancer Res; 1-8. ©2016 AACR.

  9. Nuclear corepressor 1 expression predicts response to first-line endocrine therapy for breast cancer patients on relapse

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhen-huan; Hiroko Yamashita; Tatsuya Toyama; Yutaka Yamamoto; Teru Kawasoe; Mutsuko Ibusuki; Saori Tomita; Hiroshi Sugiura; Shunzo Kobayashi; Yoshitaka Fujii; Hirotaka Iwase

    2009-01-01

    Background Estrogen receptor alpha(ER a)is the most important endocrine therapy responsiveness predictor for women with breast cancer.The accuracy of the prediction of the response to endocrine therapy was thought to be affected by involving the estrogen receptor coregulatory proteins and cross-talk between ER and other growth factor-signaling networks.Nuclear corepressor 1(NCOR1)is one of the ERa transcription repressor.The objective of the study is to investigate the expression of NCOR1 at the protein level and pursue its predictive value for breast cancer endocrine therapy.Methods In the present study,the level of expression of NCOR1 protein has been assessed by immunohistochemistry in 104 cases of invasive carcinoma of the breast.Associations between NCOR1 protein expression and different clinicopathological factors and survival were sought.Results It was found that NCOR1 was expressed at significantly higher levels in responsive patients treated with endocrine therapy as first-line treatment on relapse.Responsive patients also had a significantly longer post-relapse survival and overall survival.No NCOR1 expression difference was found between patient by age,tumor size,lymph node status,different histological grade groups and human epidermal growth factor receptor 2(HER2)status.Multivariate analysis showed that NCOR1 is an independent prognostic factor for over-all survival.Conclusions In breast cancer,NCOR1 protein expression level predicts response to endocrine therapy as first-line treatment for breast cancer patients on relapse and NCOR1 protein level assay may increase the accuracy in the endocrine treatment determination and,therefore,improving the patients survival.

  10. Update on the first-line treatment for Helicobacter pylori infection - a continuing challenge from an old enemy.

    Science.gov (United States)

    Huang, Chih-Chieh; Tsai, Kuo-Wang; Tsai, Tzung-Jiun; Hsu, Ping-I

    2017-01-01

    Because the prevalence of antibiotic resistance markedly increases with time worldwide, anti-H. pylori treatment is continuing to be a great challenge forsphysicians in clinical practice. The Real-world Practice & Expectation of Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication (REAP-HP) Survey demonstrated that the accepted minimal eradication rate of anti-H. pylori regimen in H. pylori-infected patients was 91%. The Kyoto Consensus Report on Helicobacter Pylori Gastritis also recommended that, within any region, only regimens which reliably produce eradication rates of ≥90% in that population should be used for empirical treatment. This article is aimed to review current first-line eradication regimens with a per-protocol eradication rate exceeding 90% in most geographic areas. In regions with low (≦15%) clarithromycin resistance, 14-day hybrid (or reverse hybrid), 10 ~ 14-day sequential, 7 ~ 14-day concomitant, 10 ~ 14-day bismuth quadruple or 14-day triple therapy can achieve a high eradication rate in the first-line treatment of H. pylori infection. However, in areas with high (>15%) clarithromycin resistance, standard triple therapy should be abandoned because of low eradication efficacy, and 14-day hybrid (or reverse hybrid), 10 ~ 14-day concomitant or 10 ~ 14-day bismuth quadruple therapy are the recommended regimens. If no recent data of local antibiotic resistances of H. pylori strains are available, universal high efficacy regimens such as 14-day hybrid (or reverse hybrid), concomitant or bismuth quadruple therapy can be adopted to meet the recommendation of consensus report and patients' expectation.

  11. First line antiretroviral treatment outcomes and durability in HIV-infectedchildren treatedthrough theuniversal coverage health program in Thailand.

    Science.gov (United States)

    Teeraananchai, Sirinya; Bunupuradah, Torsak; Puthanakit, Thanyawee; Kerr, Stephen J; Ruxrungtham, Kiat; Chaivooth, Suchada; Bhakeecheep, Sorakij; Law, Matthew G; Chokephaibulkit, Kulkanya

    2017-03-10

    We assessed the treatment outcomes on first-line antiretroviral therapy (ART), and factors associated with switching regimen in HIV-infected children treated through the universal coverage health program (UC) in Thailand. Children aged <15 years at ART initiation who had been receiving ART for at least 6 months between 2008 and 2014 through UC were included in the analysis. The Kaplan-Meier method was used to estimate immunological recovery (IMR), immunologic failure (IMF) and virologic failure (VF). Cox models were used to assess predictors of IMR and VF. Competing risk models were used to assess factors associated with switching to a second-line regimen, with death considered as a competing risk. A total of 4,120 children initiated ART at a median (IQR) age of 9.3 (5.8-12.0) years. The median duration of ART was 3.7 years with 17,950 person-years of follow up. 2,805 children achieved IMR and the probability of IMR increased to76% by 3 years after ART initiation. Among 1,054 children switched to second-line regimens; 84% had VF and 19% had IMF. The cumulative rate of switching regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged ≥ 12 years at ART initiation, starting with NNRTIs, and baseline CD4% < 10% had an increased risk of switching to second-line regimens. Children receiving ART through UC had good treatment outcomes, although a fifth required switching regimen by 3 years. Earlier treatment initiation and avoiding NNRTI first-line regimens in high risk children may prevent treatment failure.

  12. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Zhenzhen eHui

    2015-12-01

    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

  13. Das modale Hilfsverb "will" (The Modal Auxiliary Verb "Will")

    Science.gov (United States)

    Kunsmann, Peter W.

    1975-01-01

    That "will" and "shall" are modal, not temporal, verbs is shown by their syntactic similarity to the modals and by the fact that they follow the same transformational rules as the modals. This example demonstrates the usefulness of transformational grammar in explaining grammatical relationships to students. (Text is in…

  14. Efficacy comparison between hepatic arterial infusion chemotherapy plus systemic chemotherapy used as first-line and non-first-line treatments for the patients of colorectal cancers with unresectable hepatic metastases

    Institute of Scientific and Technical Information of China (English)

    Ping Chen; Bei Zhang; Guifang Guo; Liangping Xia; Huijuan Qiu

    2014-01-01

    Objective:The combination of hepatic arterial chemotherapy (HAIC) and systemic chemotherapy (SYC) has potential ef ect on colorectal cancer (CRC) patients with unresectable hepatic metastasis. The aim of this retrospective study was to investigate the ef icacy and safety of this combined therapeutic regimen on Chinese patients based on single institute experiences. Methods:Al 54 patients of this retrospective analysis were diagnosed with CRC with unresectable liver metas-tasis and received combined HAIC and SYC. Among the patients, 23 of them received HAIC plus SYC when they developed liver metastases as first-line treatment (Group 1), and 31 patients received HAIC plus SYC as non-first-line treatment (Group 2). The dif erent ef icacy in two groups was analyzed by SPSS 19.0. Results:The overal response rate (ORR) were 52.2%and 25.8%respectively in Groups 1 and 2 (P=0.047), and the disease control rate (DCR) were 65.2%and 35.5%respec-tively in Groups 1 and 2 (P=0.031). The median progression-free survival (PFS) were 6.8 and 3.3 months (P=0.002), the median hepatic progression-free survival (H-PFS) were 8.8 and 3.7 months (P=0.001), and the median overal survival (OS) were 18.8 and 13.7 months (P=0.121) in Groups 1 and 2, respectively. No fatal reaction was observed and no significant dif erence of adverse reaction was found in two groups. Grade 3/4 toxic ef ects included neutropenia (9.7%in Group 2 only), gastrointestinal reaction (8.7%in Group 1 and 6.5%in Group 2), stomatitis (6.5%in Group 2 only) and hyperbilirubinemia (4.3%in Group 1 only). Conclusion:HAIC combined with SYC showed promising ef icacy and safe profiles on CRC patients with unresectable liver metastases.

  15. New Modal Quantum Mechanics

    CERN Document Server

    Hollowood, Timothy J

    2013-01-01

    We describe an interpretation of quantum mechanics based on reduced density matrices of sub-systems from which the standard Copenhagen interpretation emerges as an effective description for macro-systems. The interpretation is a modal one, but does not suffer from the range of problems that plague other modal interpretations. The key feature is that quantum states carry an additional property assignment in the form of one the eigenvectors of the reduced density matrix which evolves evolves according to a stochastic process driven by the unmodified Schrodinger equation, but it is usually hidden from the emergent classical description due to the ergodic nature of its dynamics. However, during a quantum measurement, ergodicity is broken by decoherence and definite outcomes occur with probabilities that agree with the Born rule.

  16. More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments

    DEFF Research Database (Denmark)

    Kandolf Sekulovic, L.; Peris, Ketty; Hauschild, A.

    2017-01-01

    to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF...... to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p

  17. Chemotherapy versus endocrine therapy as first-line treatment in patients with luminal-like HER2-negative metastatic breast cancer: A propensity score analysis.

    Science.gov (United States)

    Bonotto, Marta; Gerratana, Lorenzo; Di Maio, Massimo; De Angelis, Carmine; Cinausero, Marika; Moroso, Stefano; Milano, Monica; Stanzione, Brigida; Gargiulo, Piera; Iacono, Donatella; Minisini, Alessandro Marco; Mansutti, Mauro; Fasola, Gianpiero; De Placido, Sabino; Arpino, Grazia; Puglisi, Fabio

    2017-02-01

    According to current guidelines, endocrine therapy (ET) is recommended as first-line treatment of luminal-like metastatic breast cancer (MBC), whereas chemotherapy (CT) should be considered in presence of life-threatening disease. In daily practice, CT is often used outside of this clinical circumstance. Factors influencing first-line choice and the relative impact on outcome are unknown. A consecutive series of luminal-like HER2-negative MBC patients treated from 2004 to 2014 was analyzed to test the association of disease- and patient-related factors with the choice of first-line treatment (ET vs. CT). A propensity score method was used to estimate impact of first-line strategy on outcome. Of 604 consecutive luminal-like MBC patients identified, 158 cases were excluded due to unknown or positive HER2-status. Among 446 HER2-negative cases, 171 (38%) received first-line CT. On multivariate analysis, the only factors significantly associated with lower CT use were old age (OR 0.25, 95%C.I. 0.13-0.49) or presence of bone metastases only (OR 0.26, 95%C.I. 0.13-0.53). In propensity score matched population, no differences were observed between CT and ET as first-line treatment either in terms of overall survival (37.5 months and 33.4 months respectively, log-rank test, P = 0.62) or progression-free survival (13.3 months and 9.9 months respectively, log-rank test, P = 0.92). High percentage of patients with luminal-like MBC received CT as first-line therapy in real-life. The choice was mainly driven by age and site of metastases. With the limitations of a non-randomized comparison, no differences on patients' outcome were observed depending on the first-line strategy. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Preferential reasoning for modal logics

    CSIR Research Space (South Africa)

    Britz, K

    2011-11-01

    Full Text Available Modal logic is the foundation for a versatile and well-established class of knowledge representation formalisms in artificial intelligence. Enriching modal logics with non-monotonic reasoning capabilities such as preferential reasoning as developed...

  19. Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Chouaïd C

    2014-12-01

    Full Text Available Christos Chouaïd,1 Perinne Crequit,2 Isabelle Borget,3 Alain Vergnenegre4 1Service de Pneumologie et de Pathologie Professionnelle, Centre Hospitalier Intercommunal Créteil et Université de Paris Est Créteil, Paris, France; 2Service de Pneumologie, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; 3Service de Biostatistique et d’Epidémiologie, Institut Gustave Roussy, Villejuif, France; 4Unité d’Oncologie Thoracique et Cutanée, Centre Hospitalier Universitaire Limoges, Limoges, France Abstract: During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC, with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs per life-year gained (LYG were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY. In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY

  20. Boosted lopinavir vs boosted atazanavir in patients failing a NNRTI first line regimen in an urban clinic in Kampala

    Directory of Open Access Journals (Sweden)

    Eva Laker

    2014-11-01

    Full Text Available Introduction: In 2011 Uganda recommended boosted atazanavir (ATV/r as the preferred PI for second line due to once daily dosing, replacing aluvia (LPV/r (1, 2. The evidence was based on the BMS O45 trial, of LPV/r vs ATV/r was performed in a high-income setting, on patients with prior PI use and resistance testing (2, 3. There are no RCTs or observational studies comparing use of ATV/r with LPV/r in patients failing NNRTI first line antiretroviral therapy in sub-Saharan Africa (3, 4. The Infectious Diseases Institute (IDI has a large second line cohort (>1838. This aims to compare clinical, immunologic and virologic response of LPV/r versus ATV/r at IDI. Methods: Retrospective cohort analysis on routinely collected data of patients switched to second line with NRTI backbones TDF/3TC or FTC, AZT/3TC, ABC/3TC from January 2009 to December 2013. Students T-tests and Chi-square tests were used in this analysis. Results: A total of 1286 (73.5% female patients were switched to LPV/r 991 (77% and ATV/r 295 (23% (p<0.001. NRTI backbones were 760 on TDF/3TC (66.8% LPV/r vs 33.2% on ATV/r, 504 on AZT/3TC (93.3% vs 6.7%, and 22 on ABC/3TC (59% vs 41%. Median (IQR time on first line for LPV/r was 21 (1–44 months and for ATV/r was 41 months (22–68. Median CD4 (IQR at switch to LPV/r was 181 cells/uL (66–424 and to ATV/r was 122 (57–238 (p≤0.001. A total of 366 patients had CD4 done at six months after switch and the mean (IQR CD4 increase was 153 (54–241 for LPV/r versus 116 (52–171 for ATV/r (p=0.232. Additionally, 304 had a CD4 at 12 months and the means were 172 (45–272 for LPV/r vs 179 (60–271 for ATV/r (p=0.426. There was no significant difference in the mean increment by NRTI backbone or by stratifying to viral load (VL at time of switch to VL <100,000 and ≥100,000. Median (IQR VL at switch was 61,000 (13,000–2,030,000 LPV/r and 51,000 (14,000_151,000 ATV/r. 269 had a VL done in the first 12 months and 178/250 (71.2% on LPV

  1. Semantic Structure of English Modals

    Science.gov (United States)

    Cook, Walter A.

    1978-01-01

    English modal verbs constitute a problem for the student of English as a foreign language. This study presents a methodology for a systematic presentation of the meaning of modal verbs. The modals "can,""may,""must," and "have to" are studied. (SW)

  2. Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment of rheumatoid arthritis. 2015 ACORDAR project.

    Science.gov (United States)

    Muñoz-Fernández, Santiago; Bustabad Reyes, María Sagrario; Calvo Alén, Jaime; Castaño Sánchez, Manuel; Chamizo Carmona, Eugenio; Corominas, Héctor; Fernández-Llanio Comella, Nagore; Hidalgo Calleja, María Cristina; Pérez Venegas, José Javier; Rodríguez Heredia, José Manuel; Romero Yuste, Susana María; Ruiz-Esquide Torino, Virginia

    2017-01-03

    To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights

  3. Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates.

    Science.gov (United States)

    Song, Zhiqiang; Zhou, Liya; Zhang, Jianzhong; He, Lihua; Bai, Peng; Xue, Yan

    2016-10-01

    Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates. This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing. Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126-30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014). Despite good compliance and

  4. An application of operational modal analysis in modal filtering

    Energy Technology Data Exchange (ETDEWEB)

    Kurowski, Piotr; Mendrok, Krzysztof; Uhl, Tadeusz, E-mail: mendrok@agh.edu.pl [AGH University of Science and Technology in Krakow, Al. Mickiewicza 30, 30-059, Krakow (Poland)

    2011-07-19

    Modal filtration in the field of damage detection has many advantages, including: its autonomous operation (without the interaction of qualified staff), low computational cost and low sensitivity to changes in external conditions. However, the main drawback of this group of damage detection methods is its limited applicability to operational data. In this paper a method of modal filter formulation from the in-operational data is described. The basis for this approach is FRFs synthesis using knowledge of the operational modal model. For that purpose a method of operational mode shape scaling is described. This is based on the measurements of several FRFs of the object. The method is then applied to the construction of modal filters and modal filtration. Additionally, the study presents verification of the method using data obtained from simulation and laboratory experiments. Verification consisted of comparing the results of modal filtering based on classical experimental modal analysis with the results of the approach proposed in the work.

  5. An application of operational modal analysis in modal filtering

    Science.gov (United States)

    Kurowski, Piotr; Mendrok, Krzysztof; Uhl, Tadeusz

    2011-07-01

    Modal filtration in the field of damage detection has many advantages, including: its autonomous operation (without the interaction of qualified staff), low computational cost and low sensitivity to changes in external conditions. However, the main drawback of this group of damage detection methods is its limited applicability to operational data. In this paper a method of modal filter formulation from the in-operational data is described. The basis for this approach is FRFs synthesis using knowledge of the operational modal model. For that purpose a method of operational mode shape scaling is described. This is based on the measurements of several FRFs of the object. The method is then applied to the construction of modal filters and modal filtration. Additionally, the study presents verification of the method using data obtained from simulation and laboratory experiments. Verification consisted of comparing the results of modal filtering based on classical experimental modal analysis with the results of the approach proposed in the work.

  6. Development and application of a SYBR green RT-PCR for first line screening and quantification of porcine sapovirus infection.

    Science.gov (United States)

    Mauroy, Axel; Van der Poel, Wim H M; der Honing, Renate Hakze-Van; Thys, Christine; Thiry, Etienne

    2012-10-17

    Sapoviruses are single stranded positive sense RNA viruses belonging to the family Caliciviridae. The virus is detected in different species including the human and the porcine species as an enteric pathogen causing asymptomatic to symptomatic enteritis. In this study, we report the development of a rapid real time qRT-PCR based on SYBR Green chemistry for the diagnosis of porcine sapovirus infection in swine. The method allows the detection of porcine sapoviruses and the quantification of the genomic copies present in stool samples. During its development, the diagnostic tool showed good correlation compared with the gold standard conventional RT-PCR and was ten-fold more sensitive. When the method was applied to field samples, porcine noroviruses from genogroup 2 genotype 11b were also detected. The method was also applied to swine samples from the Netherlands that were positive for PoSaV infection. Phylogenetic results obtained from the samples showed that PoSaV sequences were genetically related to the currently described genogroup III, to the proposed genogroup VII and also to the MI-QW19 sequence (close to the human SaV sequences). A rapid, sensitive, and reliable diagnosis method was developed for porcine sapovirus diagnosis. It correlated with the gold standard conventional RT-PCR. Specificity was good apart for genogroup 2 genotype 11b porcine noroviruses. As a first line screening diagnosis method, it allows a quicker and easier decision on doubtful samples.

  7. Selection of first-line i.v. antibiotics for acute pyelonephritis in patients requiring emergency hospital admission.

    Science.gov (United States)

    Yasufuku, Tomihiko; Shigemura, Katsumi; Yamashita, Masuo; Arakawa, Soichi; Fujisawa, Masato

    2011-04-01

    Febrile urinary tract infections (UTIs) often require the intravenous infusion of antibiotics and/or hospitalization. Acute pyelonephritis (AP) is one of the most severe forms of UTI, and the antibiotics we should use as the first line and the risk factors for treatment failure remain controversial. The objective of this study was to investigate the efficacy of i.v. antibiotics selected for the treatment of febrile AP and to examine the risk factors for antibiotic resistance. We set risk factors for antibiotic treatment failure such as age, sex, and the presence of underlying urinary tract disease. We classified all cases into 49 cases of complicated AP and 24 cases of uncomplicated AP according to the presence of underlying urinary tract diseases, and examined the characteristics of the patients and the efficacy of the antibiotics used in this study. We investigated risk factors which relate to initial treatment failure and the duration of antibiotic treatment. Initial antibiotic treatment failure was significantly correlated to C-reactive protein in complicated AP and to positive blood culture in uncomplicated AP. We revealed a significant correlation between the duration of the given antibiotics and diabetes mellitus or positive blood culture in uncomplicated AP, and tazobactam/piperacillin was significantly related to prolongation of antibiotic treatment in complicated AP. In conclusion, in this study, a positive blood culture was the representative risk factor that related to both initial treatment failure and longer duration of the given antibiotics in uncomplicated AP.

  8. Development and application of a SYBR green RT-PCR for first line screening and quantification of porcine sapovirus infection

    Directory of Open Access Journals (Sweden)

    Mauroy Axel

    2012-10-01

    Full Text Available Abstract Background Sapoviruses are single stranded positive sense RNA viruses belonging to the family Caliciviridae. The virus is detected in different species including the human and the porcine species as an enteric pathogen causing asymptomatic to symptomatic enteritis. In this study, we report the development of a rapid real time qRT-PCR based on SYBR Green chemistry for the diagnosis of porcine sapovirus infection in swine. Results The method allows the detection of porcine sapoviruses and the quantification of the genomic copies present in stool samples. During its development, the diagnostic tool showed good correlation compared with the gold standard conventional RT-PCR and was ten-fold more sensitive. When the method was applied to field samples, porcine noroviruses from genogroup 2 genotype 11b were also detected. The method was also applied to swine samples from the Netherlands that were positive for PoSaV infection. Phylogenetic results obtained from the samples showed that PoSaV sequences were genetically related to the currently described genogroup III, to the proposed genogroup VII and also to the MI-QW19 sequence (close to the human SaV sequences. Conclusions A rapid, sensitive, and reliable diagnosis method was developed for porcine sapovirus diagnosis. It correlated with the gold standard conventional RT-PCR. Specificity was good apart for genogroup 2 genotype 11b porcine noroviruses. As a first line screening diagnosis method, it allows a quicker and easier decision on doubtful samples.

  9. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  10. Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight.

    Science.gov (United States)

    Román Ivorra, José Andrés; Ivorra, José; Monte-Boquet, Emilio; Canal, Cristina; Oyagüez, Itziar; Gómez-Barrera, Manuel

    2016-01-01

    The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (€21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (€20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45-49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach €20,000 in two years. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer.

    Science.gov (United States)

    McCormack, Paul L

    2013-09-01

    Pertuzumab (Perjeta®) is a humanized anti-HER2 monoclonal antibody that binds to the extracellular dimerization subdomain of the HER2 receptor and reduces HER2 intracellular signalling by preventing HER2 from forming heterodimers with other HER receptors. Inhibition of HER2 signalling results in a reduction of tumour cell proliferation, invasiveness and survival. Pertuzumab and trastuzumab bind to different sites on the HER2 receptor and have complementary antitumour activities; they act synergistically in inhibiting the growth of HER2-overexpressing breast cancer cell lines in vitro. The efficacy of intravenous pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) in combination with trastuzumab plus docetaxel in the first-line treatment of HER2-positive metastatic breast cancer was demonstrated in the randomized, double-blind, placebo-controlled, multinational, phase III CLEOPATRA trial. Pertuzumab in combination with trastuzumab and docetaxel significantly increased independently assessed median progression-free survival (primary endpoint), objective response rate and overall survival compared with placebo in combination with trastuzumab and docetaxel. Pertuzumab had an acceptable tolerability profile when added to trastuzumab and docetaxel in the pivotal CLEOPATRA trial. Thus, pertuzumab is a valuable addition to the growing list of anti-HER2 targeted therapies for breast cancer.

  12. An ANOCEF genomic and transcriptomic microarray study of the response to radiotherapy or to alkylating first-line chemotherapy in glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Ducray François

    2010-09-01

    Full Text Available Abstract Background The molecular characteristics associated with the response to treatment in glioblastomas (GBMs remain largely unknown. We performed a retrospective study to assess the genomic characteristics associated with the response of GBMs to either first-line chemotherapy or radiation therapy. The gene expression (n = 56 and genomic profiles (n = 67 of responders and non-responders to first-line chemotherapy or radiation therapy alone were compared on Affymetrix Plus 2 gene expression arrays and BAC CGH arrays. Results According to Verhaak et al.'s classification system, mesenchymal GBMs were more likely to respond to radiotherapy than to first-line chemotherapy, whereas classical GBMs were more likely to respond to first-line chemotherapy than to radiotherapy. In patients treated with radiation therapy alone, the response was associated with differential expression of microenvironment-associated genes; the expression of hypoxia-related genes was associated with short-term progression-free survival ( 10 months. Consistently, infiltration of the tumor by both CD3 and CD68 cells was significantly more frequent in responders to radiotherapy than in non-responders. In patients treated with first-line chemotherapy, the expression of stem-cell genes was associated with resistance to chemotherapy, and there was a significant association between response to treatment and p16 locus deletions. Consistently, in an independent data set of patients treated with either radiotherapy alone or with both radiotherapy and adjuvant chemotherapy, we found that patients with the p16 deletion benefited from adjuvant chemotherapy regardless of their MGMT promoter methylation status, whereas in patients without the p16 deletion, this benefit was only observed in patients with a methylated MGMT promoter. Conclusion Differential expression of microenvironment genes and p16 locus deletion are associated with responses to radiation therapy and to first-line

  13. Semi-quantitative analysis of salivary gland scintigraphy in Sjögren's syndrome diagnosis: a first-line tool.

    Science.gov (United States)

    Angusti, Tiziana; Pilati, Emanuela; Parente, Antonella; Carignola, Renato; Manfredi, Matteo; Cauda, Simona; Pizzigati, Elena; Dubreuil, Julien; Giammarile, Francesco; Podio, Valerio; Skanjeti, Andrea

    2017-01-03

    The aim of this study was the assessment of semi-quantified salivary gland dynamic scintigraphy (SGdS) parameters independently and in an integrated way in order to predict primary Sjögren's syndrome (pSS). Forty-six consecutive patients (41 females; age 61 ± 11 years) with sicca syndrome were studied by SGdS after injection of 200 MBq of pertechnetate. In sixteen patients, pSS was diagnosed, according to American-European Consensus Group criteria (AECGc). Semi-quantitative parameters (uptake (UP) and excretion fraction (EF)) were obtained for each gland. ROC curves were used to determine the best cut-off value. The area under the curve (AUC) was used to estimate the accuracy of each semi-quantitative analysis. To assess the correlation between scintigraphic results and disease severity, semi-quantitative parameters were plotted versus Sjögren's syndrome disease activity index (ESSDAI). A nomogram was built to perform an integrated evaluation of all the scintigraphic semi-quantitative data. Both UP and EF of salivary glands were significantly lower in pSS patients compared to those in non-pSS (p quantitative parameters and ESSDAI. The proposed nomogram accuracy was 87%. SGdS is an accurate and reproducible tool for the diagnosis of pSS. ESSDAI was not shown to be correlated with SGdS data. SGdS should be the first-line imaging technique in patients with suspected pSS.

  14. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Foà, Robin; Del Giudice, Ilaria; Cuneo, Antonio; Del Poeta, Giovanni; Ciolli, Stefania; Di Raimondo, Francesco; Lauria, Francesco; Cencini, Emanuele; Rigolin, Gian Matteo; Cortelezzi, Agostino; Nobile, Francesco; Callea, Vincenzo; Brugiatelli, Maura; Massaia, Massimo; Molica, Stefano; Trentin, Livio; Rizzi, Rita; Specchia, Giorgina; Di Serio, Francesca; Orsucci, Lorella; Ambrosetti, Achille; Montillo, Marco; Zinzani, Pier Luigi; Ferrara, Felicetto; Morabito, Fortunato; Mura, Maria Angela; Soriani, Silvia; Peragine, Nadia; Tavolaro, Simona; Bonina, Silvia; Marinelli, Marilisa; De Propris, Maria Stefania; Starza, Irene Della; Piciocchi, Alfonso; Alietti, Alessandra; Runggaldier, Eva Josephine; Gamba, Enrica; Mauro, Francesca Romana; Chiaretti, Sabina; Guarini, Anna

    2014-05-01

    In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients. Copyright © 2014 Wiley Periodicals, Inc.

  15. Short term outcomes of topiramate monotherapy as a first-line treatment in newly diagnosed West syndrome

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    Gyu Min Lee

    2011-09-01

    Full Text Available Purpose : To investigate the efficacy of topiramate monotherapy in West syndrome prospectively. Methods : The study population included 28 patients (15 male and 13 female children aged 2 to 18 months diagnosed with West syndrome. After a 2-week baseline period for documentation of the frequency of spasms, topiramate was initiated at 2 mg/kg/day. The dose was increased by 2 mg/kg every week to a maximum of 12 mg/ kg/day. Clinical assessment was based on the parents’ report and a neurological examination every 2 weeks for the first 2 months of treatment. The baseline electroencephalograms (EEGs were compared with the post-treatment EEGs at 2 weeks and 1 month. Results : West syndrome was considered to be cryptogenic in 7 of the 28 patients and symptomatic in 21 patients. After treatment, 11 patients (39% became spasm-free, 6 (21% had more than 50% spasmsreduction, 3 (11% showed less than 50% reduction, and 8 (29% did not respond. The effective daily dose for achieving more than 50% reduction in spasm frequency, including becoming spasm-free, was found to be 5.8±1.1 mg/kg/day. Nine patients (32% showed complete disappearance of spasms and hypsarrhythmia, and 11 (39% showed improved EEG results. Despite adverse events (4 instances of irritability, 3 of drowsiness, and 1 of decreased feeding, no patients discontinued the medication. Conclusion : Topiramate monotherapy seems to be effective and well tolerated as a first line therapy for West syndrome and is not associated with serious adverse effects.

  16. Toxicity associated with stavudine dose reduction from 40 to 30 mg in first-line antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Mar Pujades-Rodríguez

    Full Text Available BACKGROUND: To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART for HIV treatment and to investigate associated risk factors. METHODS: Multicohort study including 23 HIV programs in resource-limited countries. Adults enrolled between January 2005 and December 2009. Four-year rates of all-cause and stavudine-specific toxicity were estimated. Multilevel mixed-effect Poisson and accelerated failure models were used to investigate factors associated with toxicity and timing of diagnosis. FINDINGS: A total of 48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause toxicity was 7.80 (95%CI 7.59-8.03 per 100 person-years, but varied greatly across sites (range 0.41-21.76. Patients treated with stavudine 40 mg had higher rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year. Women, older age, initial advanced clinical stage, and low CD4 count were associated with increased toxicity rate ratios. Timing of lipodystrophy and peripheral neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and 0.07, respectively. INSTERPRETATION: Higher rates of drug-related toxicity were reported in patients receiving stavudine 40 mg compared with 30 mg, and the time to toxicity diagnosis was shorter in patients treated with the higher dose. Higher rates of toxicity were observed during the first two years of ART.

  17. Current problems in the first-line treatment of metastatic breast cancer: focus on the role of docetaxel

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    Filippo Montemurro

    2010-09-01

    Full Text Available Metastatic breast cancer is a very heterogeneous disease, both from a clinical and a biological point of view. Despite being still incurable, the expanding therapeutic repertoire has determined a progressive increase in median survival. We describe the clinical course of a 67-year-old woman with a locally advanced, hormone-receptor positive breast cancer with synchronous liver metastases. Single-agent docetaxel at the dose of 100 mg/m2 for 8 cycles determined a pathological complete remission in the breast and a near complete remission of liver metastases. After more than 4 years from diagnosis, the patient is alive and without signs of tumour progression. Based on this clinical case, we discuss management issues like the choice of the initial treatment, the use of monochemotherapy vs polychemotherapy, the worth of surgery of the primary tumour in patients with stage IV disease, and the issue of maintenance endocrine therapy. Furthermore, we reviewed the pivotal role of docetaxel in the management of advanced breast cancer. Whether monochemotherapy or polychemotherapy is felt to be an adequate choice in the clinical practice, docetaxel qualifies as one of the most active and manageable agents. Single agent activity ranging from 20-48% in terms of response rate has been reported in several clinical trials in patients treated in various clinical settings. Docetaxel-based combinations with other cytotoxic agents have become established in the first line treatment both in patients with anthracycline-resistant and anthracycline-sensitive metastatic breast cancer. Finally, docetaxel has been shown to be an optimal companion drug for biologically targeted agents like trastuzumab or bevacizumab, resulting in further treatment options.

  18. Quadruple-first line drug resistance in Mycobacterium tuberculosis in Vietnam: What can we learn from genes?

    Science.gov (United States)

    Nguyen, Huy Quang; Nguyen, Nhung Viet; Contamin, Lucie; Tran, Thanh Hoa Thi; Vu, Thuong Thi; Nguyen, Hung Van; Nguyen, Ngoc Lan Thi; Nguyen, Son Thai; Dang, Anh Duc; Bañuls, Anne-Laure; Nguyen, Van Anh Thi

    2017-02-21

    In Vietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant (MDR)-TB burdens (7.8/100.000 population), little is known about the molecular signatures of drug resistance in general and more particularly of second line drug (SLD) resistance. This study is specifically focused on Mycobacterium tuberculosis isolates resistant to four first-line drugs (FLDs) that make TB much more difficult to treat. The aim is to determine the proportion of SLD resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance (XDR). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) FLD resistant and 55 susceptible isolates were included. Spoligotyping and 24-locus MIRU-VNTR techniques were performed and 9 genes and promoters linked to FLD and SLD resistance were sequenced. SLD susceptibility testing was carried out on a subsample of isolates. High proportion of quadruple-FLD resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (30.2%) by drug susceptibility testing. The sequencing revealed high mutation diversity with prevailing mutations at positions katG315, inhA-15, rpoB531, embB306, rrs1401, rpsL43 and gyrA94. The sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (<69%). The mutation patterns revealed 23.1% of pre-XDR and 7.7% of XDR isolates, mostly belonging to Beijing family. The genotypic diversity and the variety of mutations reflect the existence of various evolutionary paths leading to FLD and SLD resistance. Nevertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored.

  19. First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

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    Shu Yong-Qian

    2010-09-01

    Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

  20. In vitro pharmacological interaction of caffeine and first-line antibiotics is antagonistic against clinically important bacterial pathogens.

    Science.gov (United States)

    Olajuyigbe, Olufunmiso O; Adeoye-Isijola, Morenike O; Okon, Victoria; Adedayo, Otunola; Coopoosamy, Roger M

    2017-01-01

    The in vitro antibacterial activity of pure caffeine powder and its interaction with first line antibiotic against bacterial isolates were investigated with the macrobroth dilution and the checkerboard assay methods. This study showed that caffeine and the antibiotics exhibited various degrees of antibacterial activities. While caffeine had MICs ranging between 67.19 and 268.75 µg/ml, chloramphenicol was characterized by MICs between 0.98 and 31.25 µg/ml, kanamycin - 15.63-62.5 µg/ml, nalidixic acid - 0.49-250 µg/ml, erythromycin - 0.49-62.5 µg/ml, tetracycline - 1.99-62.5 µg/ml and metronidazole - 15.63-31.25 µg/ml. Combining ½ MICs and MICs of caffeine with the antibiotics as well as direct combination of caffeine and the antibiotics resulted in significant reduction of antibiotics' effectiveness. The fractional inhibitory concentration index (FICI) for the combination of ½ MICs of caffeine with different antibiotics showed antagonistic interactions with the antibiotics except kanamycin which had additive and indifferent interactions with caffeine. The FICI of the MICs of caffeine combined with antibiotics showed a reduction in the number of antagonistic interactions as chloramphenicol, nalidixic acid and erythromycin showed some indifferent interactions while kanamycin was the only antibiotic that showed indifferent interaction against all the bacterial isolates. The direct combination of caffeine and the antibiotics resulted in significant antagonistic interactions higher than in the case when caffeine, at the ½ MICs and MICs, was combined with the antibiotics. Although caffeine demonstrated significant antibacterial activity against the selected bacterial isolates, its combination with the selected antibiotics resulted in significant antagonistic interactions. Caffeine should not be combined with antibiotics as this could result in serious therapeutic failure and, possibly, drug toxicity in vivo.

  1. Comparison of therapeutic effects between EGFR-TKI in first-line and second-line therapy in non-small cell lung cancer (NSCLC patients

    Directory of Open Access Journals (Sweden)

    Liang-an CHEN

    2011-08-01

    Full Text Available Platinum-based chemotherapy is still the standard first-line treatment for patients with advanced non-small cell lung cancer(NSCLC.Molecular targeted agents provide a new option for NSCLC patients.Clinical trial had shown that survival rate with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI treatment was not inferior compared with platinum-based chemotherapy in second line NSCLC therapy.However,for the patients with EGFR gene mutation,a better outcome has been achieved with the use of EGFR-TKI as first-line treatment.Currently,controversy still exists in the use of EGFR-TKI for treatment of NSCLC as first-line or second-line therapy.In present paper,the optimal time to use EGFR-TKI for treatment of NSCLC has been discussed based on the analysis of a series of clinical trials.

  2. Modal aerosol dynamics modeling

    Energy Technology Data Exchange (ETDEWEB)

    Whitby, E.R.; McMurry, P.H.; Shankar, U.; Binkowski, F.S.

    1991-02-01

    The report presents the governing equations for representing aerosol dynamics, based on several different representations of the aerosol size distribution. Analytical and numerical solution techniques for these governing equations are also reviewed. Described in detail is a computationally efficient numerical technique for simulating aerosol behavior in systems undergoing simultaneous heat transfer, fluid flow, and mass transfer in and between the gas and condensed phases. The technique belongs to a general class of models known as modal aerosol dynamics (MAD) models. These models solve for the temporal and spatial evolution of the particle size distribution function. Computational efficiency is achieved by representing the complete aerosol population as a sum of additive overlapping populations (modes), and solving for the time rate of change of integral moments of each mode. Applications of MAD models for simulating aerosol dynamics in continuous stirred tank aerosol reactors and flow aerosol reactors are provided. For the application to flow aerosol reactors, the discussion is developed in terms of considerations for merging a MAD model with the SIMPLER routine described by Patankar (1980). Considerations for incorporating a MAD model into the U.S. Environmental Protection Agency's Regional Particulate Model are also described. Numerical and analytical techniques for evaluating the size-space integrals of the modal dynamics equations (MDEs) are described. For multimodal logonormal distributions, an analytical expression for the coagulation integrals of the MDEs, applicable for all size regimes, is derived, and is within 20% of accurate numerical evaluation of the same moment coagulation integrals. A computationally efficient integration technique, based on Gauss-Hermite numerical integration, is also derived.

  3. No Can Do Modal Verbs

    Directory of Open Access Journals (Sweden)

    Gašper Ilc

    2008-06-01

    Full Text Available The paper presents the systems of modal verbs in Slovene and English, and it focuses on comprehension and usage problems that advanced students of English may have when dealing with modal verb constructions. The paper identifies the key factors that give rise to various problems, such as in-vacuo vs. in-context treatment of modal verbs and absolute vs. relative temporal relations. It is argued that most students fail to fully understand contextualised modal verb constructions mostly due to the polysemy of modal verbs as well as their relative tense value. This is particularly the case when a (narrative text containing modal verb constructions has a past time reference, and combines different narrative techniques.

  4. First-line nurse administrators in academe: how are they prepared, what do they do, and will they stay in their jobs?

    Science.gov (United States)

    Princeton, J C; Gaspar, T M

    1991-01-01

    This article examines the role characteristics, responsibilities, and anticipated career patterns of first-line nurse administrators employed in university-based nursing education programs throughout the nation. First-line administration is the first level on the administrative ladder, and these administrators are most frequently entitled department chairpersons; division, program, and level directors; or coordinators. This was an exploratory and descriptive research project, and the questions addressed were (1) How are first-line nurse administrators in academe formally educated and informally prepared for their administrative role? (2) What are the administrative competencies important for this administrative role? (3) What strains, conflicts, and work overload are associated with the first-line administrative role, and what strategies are used to cope? (4) What do these administrators anticipate as a career pattern in administration based on their experiences as first-line administrators? Fifty-six first-line nurse administrators were interviewed from 42 schools of nursing that offer both bachelor's degree and graduate nursing programs. Data indicated that one third of the study participants completed graduate level courses in administration, and the majority had worked with administrative mentors. They ranked having character and integrity as their most important competency, which was defined as being trusted by faculty, other administrators, and students. Settling priorities for their administrative work caused them their greatest strain, and work overload was most predominant. Role conflict was present consistently as they attempted to meet the traditional triad of faculty responsibilities (research and scholarship, teaching, service) plus administrative duties. Numerous time-management strategies were used to cope, but nonetheless, one half will not continue in an administration career pathway. Implications for academic nurse administrators are cited.

  5. P11: 18FDG-PET/CT for early prediction of response to first line platinum chemotherapy in advanced thymic epithelial tumors

    Science.gov (United States)

    Palmieri, Giovannella; Ottaviano, Margaret; Del Vecchio, Silvana; Segreto, Sabrina; Tucci, Irene; Damiano, Vincenzo

    2015-01-01

    Background To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiological markers, to predict the response disease to first line platinum based chemotherapy in advanced thymic epithelial tumors (TETs). Methods Twenty patients with diagnosis of TET and stage of disease III and IV sec, Masaoka-Koga, were retrospectively included in this monocentric study. Different pre-treatment clinical, biological and pathological parameters, including histotype sec, WHO 2004 and stage of disease sec, Masaoka-Koga were assessed. Tumor glucose metabolism at baseline and its change after the first line platinum based chemotherapy (from 4 to 6 cycles) were assessed using FDG-PET, moreover the response disease was assessed using total body CT scan for the evaluation of RECIST criteria 1.1. Results Twelve patients had an objective response to the first line platinum based chemotherapy according RECIST criteria 1.1 and all of them started with a SUVmax at baseline major than 5, indeed the other eight patients, non-responders to chemotherapy, had a SUVmax at baseline minor than 5. Conclusions It is important to define the chemosensitivity of advanced TETs early. Combining bio-pathological parameters with the metabolism at baseline assessed with FDG-PET can help the physician to early predict the probability of obtaining a disease response to first line platinum based chemotherapy. The SUVmax cut off of 5 at 18FDG-PET/CT performed at baseline treatment might be a new parameter for choosing the most powerful first line of chemotherapy. Given these results, further prospective studies are needed to establish a new first line therapy in advanced TETs with a low SUVmax at baseline, non-responders to conventional chemotherapy.

  6. On Modal Refinement and Consistency

    DEFF Research Database (Denmark)

    Nyman, Ulrik; Larsen, Kim Guldstrand; Wasowski, Andrzej

    2007-01-01

    Almost 20 years after the original conception, we revisit several fundamental question about modal transition systems. First, we demonstrate the incompleteness of the standard modal refinement using a counterexample due to Hüttel. Deciding any refinement, complete with respect to the standard...... notions of implementation, is shown to be computationally hard (co-NP hard). Second, we consider four forms of consistency (existence of implementations) for modal specifications. We characterize each operationally, giving algorithms for deciding, and for synthesizing implementations, together...

  7. Cross-market cost-effectiveness analysis of erlotinib as first-line maintenance treatment for patients with stable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2012-01-01

    Full Text Available Alain Vergnenègre1, Joshua A Ray2, Christos Chouaid3, Francesco Grossi4, Helge G Bischoff5, David F Heigener6, Stefan Walzer21Department of Pneumology, Hôpital du Cluzeau, Limoges, France; 2Global Health Economics and Strategic Pricing, F Hoffmann-La Roche Ltd, Basel, Switzerland; 3Respiratory Service, Hôpital Saint Antoine, Paris, France; 4Lung Cancer Unit, National Institute for Cancer Research, Genoa, Italy; 5Thoracic Oncology, Onkologie Thoraxklinik Heidelberg, Heidelberg, Germany; 6Department of Thoracic Oncology, Krankenhaus Großhansdorf, Großhansdorf, GermanyBackground: Platinum-doublet, first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC is limited to 4–6 cycles. An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy. Erlotinib was approved for first-line maintenance in a stable disease population following results from a randomized, controlled Phase III trial comparing erlotinib with best supportive care. We aimed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease.Methods: An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN (SequentiAl Tarceva in UnResectable NSCLC study. An area under the curve model was developed; all patients entered the model in the progression-free survival health state and, after each month, moved to progression or death. A time horizon of 5 years was used. The model was conducted from the perspective of national health care payers in France, Germany, and Italy. Probabilistic sensitivity analyses were performed.Results: Treatment with erlotinib in first-line maintenance resulted in a mean life expectancy of 1.39 years in all countries

  8. Immunological failure of first-line and switch to second-line antiretroviral therapy among HIV-infected persons in Tanzania: analysis of routinely collected national data

    OpenAIRE

    Vanobberghen, FM; Kilama, B; Wringe, A; Ramadhani, A; Zaba, B; Mmbando, D; J. Todd

    2015-01-01

    Objectives Rates of first-line treatment failure and switches to second-line therapy are key indicators for national HIV programmes. We assessed immunological treatment failure defined by WHO criteria in the Tanzanian national HIV programme. Methods We included adults initiating first-line therapy in 2004–2011 with a pre-treatment CD4 count, and ≥6-months of follow-up. We assessed subhazard ratios (SHR) for immunological treatment failure, and subsequent switch to second-line therapy, using c...

  9. Load Estimation from Modal Parameters

    DEFF Research Database (Denmark)

    Aenlle, Manuel López; Brincker, Rune; Fernández, Pelayo Fernández;

    2007-01-01

    In Natural Input Modal Analysis the modal parameters are estimated just from the responses while the loading is not recorded. However, engineers are sometimes interested in knowing some features of the loading acting on a structure. In this paper, a procedure to determine the loading from a FRF...... matrix assembled from modal parameters and the experimental responses recorded using standard sensors, is presented. The method implies the inversion of the FRF which, in general, is not full rank matrix due to the truncation of the modal space. Furthermore, some ecommendations are included to improve...

  10. Level of suboptimal adherence to first line antiretroviral treatment & its determinants among HIV positive people in India

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    Beena Joshi

    2014-01-01

    Full Text Available Background & objectives: National Anti-retroviral treatment (ART programme in India was launched in 2004. Since then, there has been no published country representative estimate of suboptimal adherence among people living with HIV (PLHIV on first line ART in public settings. Hence a multicentric study was undertaken in 15 States of India to assess the level of suboptimal adherence and its determinants among PLHIV. Methods: Using a prospective observational study design, 3285 PLHIV were enrolled and followed up to six months across 30 ART centres in India. Adherence was assessed using pill count and self-reported recall method and determinants of suboptimal adherence were explored based on the responses to various issues as perceived by them. Results: Suboptimal adherence was found in 24.5 per cent PLHIV. Determinants of suboptimal adherence were illiteracy (OR-1.341, CI-1.080-1.665 , on ART for less than 6 months (OR-1.540, CI- 1.280-1.853, male gender (OR for females -0.807, CI- 0.662-0.982, tribals (OR-2.246, CI-1.134-4.447, on efavirenz (EFA regimen (OR- 1.479, CI - 1.190 - 1.837, presence of anxiety (OR- 1.375, CI - 1.117 - 1.692, non-disclosure of HIV status to family (OR- 1.549, CI - 1.176 - 2.039, not motivated for treatment (OR- 1.389, CI - 1.093 - 1.756, neglect from friends (OR-1.368, CI-1.069-1.751, frequent change of residence (OR- 3.373, CI - 2.659 - 4.278, travel expenses (OR- 1.364, CI - 1.138-1.649, not meeting the PLHIV volunteer/community care coordinator at the ART center (OR-1.639, CI-1.330-2.019. Interpretation & conclusions: To enhance identification of PLHIV vulnerable to suboptimal adherence, the existing checklist to identify the barriers to adherence in the National ART Guidelines needs to be updated based on the study findings. Quality of comprehensive adherence support services needs to be improved coupled with vigilant monitoring of adherence measurement.

  11. Next-Generation EGFR Tyrosine Kinase Inhibitors for Treating EGFR-Mutant Lung Cancer beyond First Line.

    Science.gov (United States)

    Sullivan, Ivana; Planchard, David

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) against the human epidermal growth factor receptor (EGFR) are now standard treatment in the clinic for patients with advanced EGFR mutant non-small-cell lung cancer (NSCLC). First-generation EGFR TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR tyrosine kinase domain, have resulted in a significant improvement in outcome for NSCLC patients with activating EGFR mutations (L858R and Del19). However, after a median duration of response of ~12 months, all patients develop tumor resistance, and in over half of these patients this is due to the emergence of the EGFR T790M resistance mutation. The second-generation EGFR/HER TKIs were developed to treat resistant disease, targeting not only T790M but EGFR-activating mutations and wild-type EGFR. Although they exhibited promising anti-T790M activity in the laboratory, their clinical activity among T790M+ NSCLC was poor mainly because of dose-limiting toxicity due to simultaneous inhibition of wild-type EGFR. The third-generation EGFR TKIs selectively and irreversibly target EGFR T790M and activating EGFR mutations, showing promising efficacy in NSCLC resistant to the first- and second-generation EGFR TKIs. They also appear to have lower incidences of toxicity due to the limited inhibitory effect on wild-type EGFR. Currently, the first-generation gefitinib and erlotinib and second-generation afatinib have been approved for first-line treatment of metastatic NSCLC with activating EGFR mutations. Among the third-generation EGFR TKIs, osimertinib is today the only drug approved by the Food and Drug Administration and the European Medicines Agency to treat metastatic EGFR T790M NSCLC patients who have progressed on or after EGFR TKI therapy. In this review, we summarize the available post-progression therapies including third-generation EGFR inhibitors and combination treatment strategies for treating patients with NSCLC harboring EGFR mutations and address the

  12. Nanoparticle albumin-bound paclitaxel combined with cisplatin as the first-line treatment for metastatic esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shi Y

    2013-05-01

    Full Text Available Yan Shi, Rui Qin, Zhi-Kuan Wang, Guang-Hai DaiDepartment of Multimodality Therapy of Oncology, General Hospital of CPLA, Beijing, People's Republic of ChinaAbstract: Esophageal cancer is a major health hazard in many parts of the world and is often diagnosed late. The objective of this study was to explore the efficacy and safety of nanoparticle albumin-bound paclitaxel (Nab-PTX combined with cisplatin (DDP in patients with metastatic esophageal squamous cell carcinoma (ESCC. Patients with histologically confirmed ESCC were treated with Nab-PTX 250 mg/m2 and DDP 75 mg/m2 intravenously on day 1, every 21 days. Evaluation was performed after every two cycles of therapy and the therapy was continued until disease progression or unacceptable toxicity. From April 2010 to December 2012, 33 patients were enrolled. Ten patients had recurrent and metastatic tumors after surgery and 23 patients were diagnosed with unresectable metastatic disease. Patients received a median of four cycles of therapy (ranging from two to six cycles. Twenty patients achieved partial response and nine patients achieved stable disease; no complete response was observed. The objective response rate was 60.6% and the disease control rate was 87.9%. The median progression-free survival was 6.2 months (95% confidence interval: 4.0 to 8.4 months and the median overall survival was 15.5 months (95% CI: 7.6 to 23.4 months. Only four patients experienced grade 3 adverse events, including vomiting, neutropenia, and sensory neuropathy. The most common adverse events were nausea/vomiting (81.8%, neutropenia (63.6%, leucopenia (48.5%, anemia (24.2% and sensory neuropathy (24.2%. In conclusion, the combination of Nab-PTX and DDP is a highly effective and well-tolerated first-line treatment in metastatic ESCC.Keywords: esophageal squamous cell carcinoma, nanoparticle albumin-bound paclitaxel, chemotherapy, metastasis

  13. Metaphysical Modality, Modality of Predicate and the Theory of

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    l nabavi

    2010-05-01

    This paper discusses the historical overview of the metaphysical modality firstly and then shows that the theory of "Decisive Necessity” is true and justified in a model of modal logic with equivalent accessibility relation and homogeneous possible world view (fixed domain.

  14. A Modal Walk Through Space

    NARCIS (Netherlands)

    Aiello, Marco; Benthem, Johan van

    2002-01-01

    We investigate the major mathematical theories of space from a modal standpoint: topology, affine geometry, metric geometry, and vector algebra. This allows us to see new fine-structure in spatial patterns which suggests analogies across these mathematical theories in terms of modal, temporal, and c

  15. Modal Logics for Cryptographic Processes

    DEFF Research Database (Denmark)

    Frendrup, U.; Huttel, Hans; Jensen, N. J.

    2002-01-01

    We present three modal logics for the spi-calculus and show that they capture strong versions of the environment sensitive bisimulation introduced by Boreale et al. Our logics differ from conventional modal logics for process calculi in that they allow us to describe the knowledge of an attacker ...

  16. Constraint methods for modal satisfiability

    NARCIS (Netherlands)

    Brand, S.; Gennari, R.; de Rijke, M.; Apt, K.R.; Fages, F.; Rossi, F.

    2004-01-01

    Modal and modal-like formalisms such as temporal or description logics go beyond propositional logic by introducing operators that allow for a guarded form of quantication over states or paths of transition systems. Thus, they are more expressive than propositional logic, yet computationally better

  17. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well as re...

  18. Treatment of multicentric or cranial mediastinal high-grade T-cell lymphoma in dogs with a first-line CCNU-L(-chlorambucil)-CHOP protocol

    NARCIS (Netherlands)

    Ossowska, M.; Teske, E.; Beirens-Van Kuijk, L.; Zandvliet, M.; De Vos, J. P.

    2016-01-01

    This retrospective study determined disease free survival (DFS) and progression free survival (PFS) in chemo-naïve dogs with multicentric or cranial mediastinal high-grade T-cell lymphoma, treated with a first-line CCNU-L(-chlorambucil)-CHOP protocol. Of thirteen dogs with multicentric lymphoma, 92.

  19. Impact of food on the pharmacokinetics of first-line anti-TB drugs in treatment-naive TB patients : a randomized cross-over trial

    NARCIS (Netherlands)

    Saktiawati, Antonia M. I.; Sturkenboom, Marieke G. G.; Stienstra, Ymkje; Subronto, Yanri W.; Sumardi, [No Value; Kosterink, Jos G. W.; van der Werf, Tjip S.; Alffenaar, Jan-Willem C.

    2016-01-01

    Concomitant food intake influences pharmacokinetics of first-line anti-TB drugs in healthy volunteers. However, in treatment-naive TB patients who are starting with drug treatment, data on the influence of food intake on the pharmacokinetics are absent. This study aimed to quantify the influence of

  20. Costs of managing adverse events in the treatment of first-line metastatic renal cell carcinoma: Bevacizumab in combination with interferon-α2a compared with sunitinib

    NARCIS (Netherlands)

    G.H.J. Mickisch; M. Gore (Martin); B. Escudier (B.); G. Procopio (G.); S. Walzer (S.); M.J.C. Nuijten (Mark)

    2010-01-01

    textabstractBackground: Bevacizumab plus interferon-α2a (IFN) prolongs progression-free survival to>10 months, which is comparable with sunitinib as first-line treatment of metastatic renal cell carcinoma (RCC). The two regimens have different tolerability profiles; therefore, costs for managing

  1. Treatment of multicentric or cranial mediastinal high-grade T-cell lymphoma in dogs with a first-line CCNU-L(-chlorambucil)-CHOP protocol

    NARCIS (Netherlands)

    Ossowska, M.; Teske, E.; Beirens-Van Kuijk, L.; Zandvliet, M.; De Vos, J. P.

    2016-01-01

    This retrospective study determined disease free survival (DFS) and progression free survival (PFS) in chemo-naïve dogs with multicentric or cranial mediastinal high-grade T-cell lymphoma, treated with a first-line CCNU-L(-chlorambucil)-CHOP protocol. Of thirteen dogs with multicentric lymphoma,

  2. The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Ter Veer, Emil; Mohammad, Nadia Haj; Lodder, Paul; Ngai, Lok Lam; Samaan, Mary; van Oijen, Martijn G H; van Laarhoven, Hanneke W M

    2016-01-01

    BACKGROUND: S-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based

  3. Cost-effectiveness of tenofovir instead of zidovudine for use in first-line antiretroviral therapy in settings without virological monitoring

    DEFF Research Database (Denmark)

    von Wyl, Viktor; Cambiano, Valentina; Jordan, Michael R

    2012-01-01

    The most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and the...

  4. Randomised phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.

    Science.gov (United States)

    Kwakman, J J M; Simkens, L H J; van Rooijen, J M; van de Wouw, A J; Ten Tije, A J; Creemers, G J M; Hendriks, M P; Los, M; van Alphen, R J; Polée, M B; Muller, E W; van der Velden, A M T; van Voorthuizen, T; Koopman, M; Mol, L; van Werkhoven, E; Punt, C J A

    2017-04-05

    Hand-foot syndrome (HFS) is a common side effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients.

  5. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Hainsworth, John D; Daugaard, Gedske; Lesimple, Thierry

    2015-01-01

    BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial, previo...

  6. Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma

    NARCIS (Netherlands)

    Hofstra, LS; Kristensen, GB; Willemse, PHB; Vindevoghel, A; Meden, H; Lahousen, M; Oberling, F; Sorbe, B; Crump, M; Sklenar, [No Value; Sluiter, WJ; Kiese, B; Trope, CG; de Vries, EGE

    1998-01-01

    Purpose: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. Patients and Methods: In a randomized multicenter study, 185 patients recei

  7. Cost-effectiveness of early treatment with first-line NNRTI-based HAART regimens in the UK, 1996-2006.

    Directory of Open Access Journals (Sweden)

    Eduard J Beck

    Full Text Available AIM: Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996-2006. BACKGROUND: Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PI(boosted regimens. METHODS: Times to first-line treatment failure and annual costs were calculated for first-line HAART regimens by CD4 count when starting HAART (2006 UK prices. Cost-effectiveness of 2NRTIs+NNRTI versus 2NRTIs+PI(boosted regimens was calculated for four CD4 strata. RESULTS: 55% of 5,541 people living with HIV (PLHIV started HAART with CD4 count ≤ 200 cells/mm3, many of whom were Black Africans. Annual treatment cost decreased as CD4 count increased; most marked differences were observed between starting HAART with CD4 ≤ 200 cells/mm3 compared with CD4 count >200 cells/mm3. 2NRTI+PI(boosted and 2NRTI+NNRTI regimens were the most effective regimens across the four CD4 strata; 2NRTI + NNRTI was cost-saving or cost-effective compared with 2NRTI + PI(boosted regimens. CONCLUSION: To ensure more effective and efficient provision of HIV services, 2NRTI+NNRTI should be started as first-line HAART regimen at CD4 counts ≤ 350 cell/mm3, unless specific contra-indications exist. This will increase the number of PLHIV receiving HAART and will initially increase population costs of providing HIV services. However, starting PLHIV earlier on cost-effective regimens will maintain them in better health and use fewer health or social services, thereby generating fewer treatment and care costs, enabling them to remain socially and economically active members of society. This does raise a number of ethical issues, which will have to be acknowledged and addressed, especially in countries with limited

  8. First-line antiretroviral treatment outcome in a patient presenting an HIV-1/2 multiclass drug resistant infection

    Directory of Open Access Journals (Sweden)

    E Castro

    2012-11-01

    week 24. Laboratory assessments showed a neutrophile drop to 0.96 at week 4, fully restored at week 9. Conclusion: This case of HIV-1/2 dual infection underscores the importance of assessing genotypic analysis of both viruses ahead to treatment choice. It also highlights viral load platforms constraints when it comes to clinical monitoring of HIV-1/2 co-infection in western settings. Overall, first-line salvage treatment was well tolerated and suppressed HIV-1 resistant clade allowing recovery of CD4+ T-cell count.

  9. Relation of early tumor shrinkage (ETS) observed in first-line treatment to efficacy parameters of subsequent treatment in FIRE-3 (AIOKRK0306).

    Science.gov (United States)

    Modest, Dominik P; Stintzing, Sebastian; Fischer von Weikersthal, Ludwig; Decker, Thomas; Kiani, Alexander; Vehling-Kaiser, Ursula; Al-Batran, Salah-Eddin; Heintges, Tobias; Lerchenmüller, Christian; Kahl, Christoph; Seipelt, Gernot; Kullmann, Frank; Scheithauer, Werner; Kirchner, Thomas; Jung, Andreas; Stauch, Martina; von Einem, Jobst Christian; Moehler, Markus; Held, Swantje; Heinemann, Volker

    2017-04-15

    We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after 6 weeks of treatment. Shrinkage was classified as ETS (shrinkage by ≥ 20%), mETS (shrinkage by 0 to 0 to ETS patients, while non-ETS was associated with less favorable outcome (mETS 24.0 (95% CI 21.2-26.9) months, mPD 19.0 (95% CI 13.0-25.0) months, PD 12.8 (95% CI 11.1-14.5) months). Differences in PFS of first-line therapy were less pronounced. ETS subgroups defined in first-line therapy also correlated with efficacy of second-line therapy. Progression-free survival in second-line (PFS2nd) was 6.5 months (5.8-7.2) for ETS, and was 5.6 (95% CI 4.7-6.5) months for mETS, 4.9 (95% CI 3.7-6.1) months for mPD and 3.3 (95% CI 2.3-4.3) months for PD. PFS of first-line and PFS2nd showed a linear correlation (Bravais-Pearson coefficient: 0.16, p = 0.006). While ETS is associated with the most favorable outcome, non-ETS represents a heterogeneous subgroup with distinct characteristics of less favorable initial tumor response to treatment. This is the first analysis to demonstrate that early tumor response observed during first-line FOLFIRI-based therapy may also relate to efficacy of second-line treatment. Early response parameters may serve as stratification factors in trials recruiting pretreated patients. © 2016 UICC.

  10. Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

    Directory of Open Access Journals (Sweden)

    Soo-Yon Rhee

    2017-04-01

    Full Text Available Tenofovir disoproxil fumarate (TDF genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs, we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

  11. Retrospective survey and evaluation of first-line antibiotics for chemotherapy-induced febrile neutropenia in patients with acute myeloid leukemia

    Science.gov (United States)

    Mukoyama, Naoki; Nakashima, Marie; Miyamura, Koichi; Yoshimi, Akira; Noda, Yukihiro; Mori, Kazuhiro

    2017-01-01

    ABSTRACT Patients with acute leukemia are susceptible to chemotherapy-induced severe myelosuppression, and therefore are at a high risk for febrile neutropenia (FN). In such cases, the use of broad-spectrum antibiotics such as fourth-generation cephalosporins and carbapenems is recommended as first-line antimicrobial treatment; however, the effectiveness of these agents in patients with acute myeloid leukemia (AML) has not been investigated in detail. We retrospectively examined and evaluated the effectiveness of first-line antibiotic treatment regimens for chemotherapy-induced FN in patients with AML in Japanese Red Cross Nagoya Daiichi Hospital. The evaluated first-line treatment regimens were as follows: cefozopran (CZOP) + amikacin (AMK) in 38 cases, cefepime (CFPM) alone in 2 cases, CFPM + AMK in 2 cases, piperacillin (PIPC) + AMK in 2 cases, and CZOP alone in 1 case. Additionally, prophylactic antifungal agents were administered in all cases. Markedly effective, effective, moderately effective, and ineffective responses occurred in 31.1%, 8.9%, 8.9%, and 51.1%, respectively, of the treated cases. The response rate, defined as the combination of markedly effective and effective outcomes, was 40.0%. In 11 cases, impairment of renal functions were observed, and they were associated with combination treatments including AMK; nine of these were associated with a glycopeptide. The combination of CZOP with AMK (84.4%) was the most commonly used first-line treatment for FN in patients with AML; carbapenem or tazobactam/PIPC has never been used for treatment of such cases. Our findings demonstrate that fourth-generation cephems will be an effective first-line treatment for FN in patients with AML in our hospital. PMID:28303057

  12. The Clinical and Economic Impact of Genotype Testing at First-line Antiretroviral Therapy Failure for HIV-Infected Patients in South Africa

    Science.gov (United States)

    Levison, Julie H.; Wood, Robin; Scott, Callie A.; Ciaranello, Andrea L.; Martinson, Neil A.; Rusu, Corina; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2013-01-01

    Background. In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type (WT) virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications International model of human immunodeficiency virus (HIV) disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs genotype, assuming availability of protease inhibitor–based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/µL, and WT virus prevalence 20%; genotype cost was $300 per test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US dollars), and incremental cost-effectiveness ratios (dollars per years of life saved [YLS]). Results. No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16 360 and $16 540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of WT virus (very cost-effective when prevalence ≥12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care ≥5 months decreased survival and made no genotype the preferred strategy. When the test cost was ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results. PMID:23087386

  13. Interpreting Metaphor of Modality in Advertising English

    Science.gov (United States)

    Xu, Jian

    2009-01-01

    Based on a review of the historical and current studies on modality, this paper aims at interpreting metaphor of modality and its functions in advertising English according to theories of modality system and metaphor of modality in systemic-functional linguistics with a corpus we have collected. It is pointed out that metaphor of modality, a usual…

  14. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy.

    Science.gov (United States)

    Bacha, Tigist; Tilahun, Birkneh; Worku, Alemayehu

    2012-08-24

    The emergence of resistance to first line antiretroviral therapy (ART) regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Data of 1186 children were analyzed. Five hundred seventy seven (48.8%) were males with a mean age of 6.22 (SD = 3.10) years. Of the 167(14.1%) children who had treatment failure, 70 (5.9%) had only clinical failure, 79 (6.7%) had only immunologic failure, and 18 (1.5%) had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR), 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4%) were switched to second line ART with a mean delay of 24 (SD = 11.67) months. The remaining 143 (85.6%) cases were diagnosed to have treatment failure retrospectively by the

  15. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Bacha Tigist

    2012-08-01

    Full Text Available Abstract Background The emergence of resistance to first line antiretroviral therapy (ART regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. Methods A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Results Data of 1186 children were analyzed. Five hundred seventy seven (48.8% were males with a mean age of 6.22 (SD = 3.10 years. Of the 167(14.1% children who had treatment failure, 70 (5.9% had only clinical failure, 79 (6.7% had only immunologic failure, and 18 (1.5% had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR, 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4% were switched to second line ART with a mean delay of 24 (SD = 11.67 months. The remaining 143 (85.6% cases were diagnosed

  16. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well...... as refutation of safety and liveness properties. However, the algorithmic construction of finite abstractions from potentially infinite concurrent processes is a missing link that prevents their more widespread usage for model checking of concurrent systems. Our algorithm is a worklist algorithm using concepts...

  17. Analysis of Competency Model for First-line Managers%基层管理者胜任力模型分析

    Institute of Scientific and Technical Information of China (English)

    覃昆

    2011-01-01

    First-line managers play a role in connecting leaders and staff in organization management,who are the executors of enterprise strategy.The advance and continuity of first-line managers' abilities have already become the key factor to realize the enterprise strategy,which is the guarantee of continues development of enterprise.Competency model gives a new standpoint to understand the roles of first-line managers.This article sets up a competency model and provides an effective evidence for recruitment,selection,training,performance appraisal and salary management aiming at the characteristic of first-line manager.%基层管理者在组织经营管理中起着承上启下的作用,是企业战略的执行者,其能力的快速提升和能力的延续性已经成为企业战略实现的关键环节,它是企业可持续发展的保证。胜任力模型为认识和理解基层管理者角色提供了新的视角,本文针对基层管理者的特点建立基层管理者胜任力模型,为各类企业基层管理者的招聘、选拔、培训、绩效考核、薪酬管理等提供有力的依据。

  18. Systematic review and meta-analysis on the prognostic value of complete remission status at FDG-PET in Hodgkin lymphoma after completion of first-line therapy.

    Science.gov (United States)

    Adams, Hugo J A; Nievelstein, Rutger A J; Kwee, Thomas C

    2016-01-01

    This study aimed to systematically review and meta-analyze the prognostic value of complete remission status at 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in Hodgkin lymphoma after completion of first-line therapy. A systematic literature search was performed in the MEDLINE database for suitable original articles. The included studies were methodologically assessed using the Quality In Prognosis Studies tool. The proportion of patients who developed disease relapse during follow-up, among those patients who were in complete remission according to FDG-PET at the completion of first-line therapy, was calculated for each included study. Heterogeneity in disease relapse proportions across individual studies was assessed using the I2 statistic, with heterogeneity regarded present if I2disease relapse proportion was calculated using either a random effects model (if I2>50) or a fixed effects model (if I2≤50). Ten studies comprising a total number of 1137 Hodgkin lymphoma patients with complete remission status according to FDG-PET after completion of first-line therapy were included. Overall methodological quality of included studies was reasonably good. The disease relapse rate during follow-up among all patients with complete remission status at end-of-treatment FDG-PET ranged from 0 to 26.7 %, with a weighted summary proportion of 7.5 % (95 % confidence interval 3.9–13.8 %) using the random effects model (I2=88.3 %). In conclusion, although the disease relapse rate in Hodgkin lymphoma patients who achieve an FDG-PET-based complete remission after first-line therapy is low from an absolute point of view, it is actually high when considering the generally favorable outcome of Hodgkin lymphoma.

  19. Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab

    DEFF Research Database (Denmark)

    Tarpgaard, Line Schmidt; Guren, Tormod K; Glimelius, Bengt

    2014-01-01

    AND METHODS: A total of 566 patients in the NORDIC VII Study were randomized 1∶1∶1 to arm A (Nordic FLOX), arm B (Nordic FLOX + cetuximab), or arm C (Nordic FLOX + cetuximab for 16 weeks followed by cetuximab alone as maintenance therapy). Pretreatment plasma samples were available from 510 patients. Plasma......: Plasma YKL-40 is an independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy alone or combined with cetuximab....

  20. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial)

    OpenAIRE

    Telekes Peter; Holm Frantisek; Slaby Josef; Aschermann Ondrej; Wiendl Martin; Kettner Jiri; Kvapil Milan; Mates Martin; Hajek Petr; Macek Milan; Kukacka Jiri; Vejvoda Jiri; Alan David; Ostadal Petr; Horak David

    2010-01-01

    Abstract Background Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome (ACS). The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear. The aim of our study was, therefore, to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS. Methods The trial was ...

  1. Treatment patterns, healthcare resource utilization, and costs following first-line antidepressant treatment in major depressive disorder: a retrospective US claims database analysis.

    Science.gov (United States)

    Gauthier, Geneviève; Guérin, Annie; Zhdanava, Maryia; Jacobson, William; Nomikos, George; Merikle, Elizabeth; François, Clément; Perez, Vanessa

    2017-06-19

    Although the symptoms of major depressive disorder (MDD) are often manageable with pharmacotherapy, response to first-line antidepressant treatment is often less than optimal. This study describes long-term treatment patterns in MDD patients in the United States and quantifies the economic burden associated with different treatment patterns following first-line antidepressant therapy. MDD patients starting first-line antidepressant monotherapy and having continuous enrollment ≥12 months before and ≥24 months following the index date (i.e., the first documented prescription fill) were selected from the Truven Health Analytics MarketScan (2003-2014) database. Based on the type of first treatment change following initiation, six treatment cohorts were defined a priori ("persistence"; "discontinuation"; "switch"; "dose escalation"; "augmentation"; and "combination"). Treatment patterns through the fourth line of therapy within each cohort, healthcare resource utilization (HCRU), and cost analyses were restricted to patients with adequate treatment duration (defined as ≥42 days) in each line (analysis sub-sample, N = 21,088). HCRU and costs were described at the cohort and pattern levels. Treatment cohorts representing patterns. Median time to discontinuation was 23 weeks. The switch cohort exhibited the highest HCRU (18.9 days with medical visits per-patient-per-year) and greatest healthcare costs ($11,107 per-patient-per-year) following the index date. Treatment patterns representing a cycling on and off treatment in the switch cohort were associated with the greatest healthcare costs overall. A high proportion of patients discontinue first-line antidepressant shortly after initiation. Patterns representing a cycling on and off treatment in the switch cohort were associated with the highest healthcare costs. These findings underscore challenges in effectively treating patients with MDD and a need for personalized patient management.

  2. Post-study therapy as a source of confounding in survival analysis of first-line studies in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Zietemann, Vera D; Schuster, Tibor; Duell, Thomas Hg

    2011-06-01

    Clinical trials exploring the long-term effects of first-line therapy in patients with advanced non-small-cell lung cancer generally disregard subsequent treatment although most patients receive second and third-line therapies. The choice of further therapy depends on critical intermediate events such as disease progression and it is usually left at the physician's discretion. Time-dependent confounding may then arise with standard survival analyses producing biased effect estimates, even in randomized trials. Herein we describe the concept of time-dependent confounding in detail and discuss whether the response to first-line treatment may be a potential time-dependent confounding factor for survival in the context of subsequent therapy. A prospective observational study of 406 patients with advanced non-small-cell lung cancer served as an example base. There is evidence that time-dependent confounding may occur in multivariate survival analysis after first-line therapy when disregarding subsequent treatment. In the light of this important but underestimated aspect some of the large and meaningful recent clinical first-line lung cancer studies are discussed, focussing on subsequent treatment and its potential impact on the survival of the study patients. No recently performed lung cancer trial applied adequate statistical analyses despite the frequent use of subsequent therapies. In conclusion, effect estimates from standard survival analysis may be biased even in randomized controlled trials because of time-dependent confounding. To adequately assess treatment effects on long-term outcomes appropriate statistical analyses need to take subsequent treatment into account.

  3. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

    DEFF Research Database (Denmark)

    Fløtten, Ø; Grønberg, B H; Bremnes, R;

    2012-01-01

    BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... of radiotherapy did not differ significantly between the treatment groups. CONCLUSION: The two regimens yielded similar overall survival. The VG combination had only a slightly better toxicity profile....

  4. Paclitaxel plus cisplatin vs. 5-fluorouracil plus cisplatin as first-line treatment for patients with advanced squamous cell esophageal cancer

    OpenAIRE

    Liu, Ying; Ren, Zhonghai; Yuan, Long; Xu, Shuning; Yao, Zhihua; Qiao, Lei; Li, Ke

    2016-01-01

    Paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin treatments are effective strategies for patients with advanced esophageal squamous cell carcinoma. This study was to evaluate the safety and efficacy of paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin as first-line chemotherapy for patients with advanced esophageal squamous cell carcinoma. A total of 398 patients with advanced esophageal squamous cell carcinoma who received chemotherapy were included and divided into 2 gr...

  5. Second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma

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    Song ZB

    2014-10-01

    Full Text Available Zhengbo Song, Yiping Zhang Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China Purpose: This retrospective analysis evaluates the clinical efficacy and toxicity of second-line docetaxel-based chemotherapy after failure of fluorouracil-based first-line treatment for advanced esophageal squamous cell carcinoma (ESCC. Methods: We retrospectively reviewed patients who had received second-line docetaxel-based chemotherapy for advanced ESCC in Zhejiang Cancer Hospital between January 2008 and December 2011. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis. Results: Eighty-five patients received docetaxel-based second-line chemotherapy after the failure of first-line fluorouracil-based treatment. Forty-four patients received docetaxel-platinum chemotherapy, and 41 received docetaxel single-agent treatment. The progression-free survival (PFS and overall survival (OS were 3.5 and 5.5 months in all of the patients, respectively. There were no statistically significant differences in PFS and OS between docetaxel-platinum and docetaxel single-agent chemotherapy groups (P-value 0.38 and 0.64, respectively. Response to first-line chemotherapy was a favorable prognostic factor for PFS in uni- and multivariate analyses (P-value 0.005 and 0.028, respectively. Conclusion: Patients with docetaxel-based second-line treatment obtained a moderate PFS advantage in advanced ESCC. Response to first-line chemotherapy was a favorable prognostic factor for PFS of second-line chemotherapy in advanced ESCC. Keywords: ESCC, efficacy, toxicity

  6. Evaluation of PET and MR datasets in integrated 18F-FDG PET/MRI: A comparison of different MR sequences for whole-body restaging of breast cancer patients.

    Science.gov (United States)

    Grueneisen, Johannes; Sawicki, Lino Morris; Wetter, Axel; Kirchner, Julian; Kinner, Sonja; Aktas, Bahriye; Forsting, Michael; Ruhlmann, Verena; Umutlu, Lale

    2017-04-01

    To investigate the diagnostic value of different MR sequences and 18F-FDG PET data for whole-body restaging of breast cancer patients utilizing PET/MRI. A total of 36 patients with suspected tumor recurrence of breast cancer based on clinical follow-up or abnormal findings in follow-up examinations (e.g. CT, MRI) were prospectively enrolled in this study. All patients underwent a PET/CT and subsequently an additional PET/MR scan. Two readers were instructed to identify the occurrence of a tumor relapse in subsequent MR and PET/MR readings, utilizing different MR sequence constellations for each session. The diagnostic confidence for the determination of a malignant or benign lesion was qualitatively rated (3-point ordinal scale) for each lesion in the different reading sessions and the lesion conspicuity (4-point ordinal scale) for the three different MR sequences was additionally evaluated. Tumor recurrence was present in 25/36 (69%) patients. All three PET/MRI readings showed a significantly higher accuracy as well as higher confidence levels for the detection of recurrent breast cancer lesions when compared to MRI alone (pbreast cancer recurrence (p>0.05), yet the highest confidence levels were obtained, when all three MR sequences were used for image interpretation. Moreover, contrast-enhanced T1-weighted VIBE imaging showed significantly higher values for the delineation of malignant and benign lesions when compared to T2w HASTE and diffusion-weighted imaging. Integrated PET/MRI provides superior restaging of breast cancer patients over MRI alone. Facing the need for appropriate and efficient whole-body PET/MR protocols, our results show the feasibility of fast and morphologically adequate PET/MR protocols. However, considering an equivalent accuracy for the detection of breast cancer recurrences in the three PET/MR readings, the application of contrast-agent and the inclusion of DWI in the study protocol seems to be debatable. Copyright © 2017 Elsevier B

  7. Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

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    Macedo Ligia

    2012-03-01

    Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

  8. Proton pump inhibitor-amoxicillin-clarithromycin versus proton pump inhibitor-amoxicillin-metronidazole as first-line Helicobacter pylori eradication therapy.

    Science.gov (United States)

    Nishizawa, Toshihiro; Suzuki, Hidekazu; Suzuki, Masayuki; Takahashi, Masahiko; Hibi, Toshifumi

    2012-09-01

    The aim of this study was to compare the efficacy and tolerability of the first-line Helicobacter pylori (H. pylori) eradication regimen composed of proton pump inhibitor, clarithromycin, and amoxicillin, with those of a regimen composed of proton pump inhibitor, metronidazole, and amoxicillin. Data of patients, who were administered the first-line H. pylori eradication regimen at Tokyo Medical Center between 2008 and 2011, were reviewed. All patients had H. pylori gastritis without peptic ulcer disease. The 7-day triple regimen composed of lansoprazole, clarithromycin, and amoxicillin was administered to 55 patients, and that composed of omeprazole, metronidazole, and amoxicillin was administered to 55 patients. Intention-to-treat and per-protocol eradication rates were 74.5 and 80.4%, respectively, for the regimen of lansoprazole, clarithromycin, and amoxicillin, whereas the corresponding rates were 96.4 and 100%, respectively, for the regimen of omeprazole, metronidazole, and amoxicillin. In conclusion, first-line H. pylori eradication therapy composed of omeprazole, metronidazole, and amoxicillin was significantly more effective than that composed of lansoprazole, clarithromycin, and amoxicillin, without differences in tolerability.

  9. Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

    Science.gov (United States)

    Chen, Hui; Zhang, Ji; Cao, Guang; Liu, Peng; Xu, Haifeng; Wang, Xiaodong; Zhu, Xu; Gao, Song; Guo, Jianhai; Zhu, Linzhong; Zhang, Pengjun

    2016-02-01

    Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials.

  10. Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Patients Treated with First-Line Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Chang, I-Shou; Jiang, Shih Sheng; Yang, James Chih-Hsin; Su, Wu-Chou; Chien, Li-Hsin; Hsiao, Chin-Fu; Lee, Jih-Hsiang; Chen, Chih-Yi; Chen, Chung-Hsing; Chang, Gee-Chen; Wang, Zhaoming; Lo, Fang-Yi; Chen, Kuan-Yu; Wang, Wen-Chang; Chen, Yuh-Min; Huang, Ming-Shyan; Tsai, Ying-Huang; Su, Yu-Chun; Hsieh, Wan-Shan; Shih, Wen-Chi; Shieh, Shwn-Huey; Yang, Tsung-Ying; Lan, Qing; Rothman, Nathaniel; Chen, Chien-Jen; Chanock, Stephen J; Yang, Pan-Chyr; Hsiung, Chao A

    2017-03-01

    Patients with non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR) are relatively sensitive to EGFR-tyrosine kinase inhibitor (TKI) treatment and have longer progression-free survival (PFS) when treated with EGFR-TKI compared with platinum-based chemotherapy. However, many patients with advanced NSCLC who have mutated EGFR do not respond to first-line EGFR-TKI treatment and still have shorter PFS. The aim of this study was to identify genetic variants associated with PFS among patients with lung adenocarcinoma who were treated with first-line EGFR-TKIs. A genome-wide association study on PFS was performed in never-smoking women diagnosed with lung adenocarcinoma and who were treated with first-line EGFR-TKIs (n = 128). Significant single-nucleotide polymorphisms (SNPs) were selected for follow-up association analysis (n = 198) and for replication assay in another independent cohort (n = 153). We identified SNPs at 4q12 associated with PFS at genome-wide significance (P Genetic variants in 4q12 merit further investigation to assess their potential as pharmacogenomic predictors for and to understand the biology underlying its influence on PFS in patients treated with TKI therapy.

  11. Minority HIV-1 resistant variants in recent infection and in patients who failed first-line antiretroviral therapy with no detectable resistance-associated mutations in Thailand.

    Science.gov (United States)

    Le Nguyen, Hai; Pitakpolrat, Patrawadee; Sirivichayakul, Sunee; Delaugerre, Constance; Ruxrungtham, Kiat

    2012-05-01

    Through the Thai National AIDS Program, approximately 200,000 patients infected with HIV are on antiretroviral (ARV) therapy. Although studies have shown low prevalence of primary HIV-1 resistance transmission in Thailand and in Southeast Asia where subtype CRF01_AE is predominant, minority HIV-1 drug resistance has not been studied. Two groups of patients, whose conventional genotyping results showed no drug resistance-associated mutations, were investigated: 104 homosexual men recently infected with HIV-1, naïve to ARV treatment and 22 first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based failure patients. Pyrosequencing (PSQ) assay was developed to detect and quantify minority Y181C and M184V variants from the patients' plasma samples. The sensitivity of PSQ to detect minority Y181C and M184V variants was approximately 1%. 1/104 (0.5%) and 3/101 (3%) samples were found harboring Y181C and M184V in the group of homosexual men recently infected with HIV-1. In patients with first-line treatment failure, one had a minority M184V mutation (4.5%). The prevalence of Y181C and M184V minority variants in homosexual men recently infected and naïve to treatment was low in Thailand. Systematic monitoring of primary resistance transmission in Thailand and this region is essential to guide whether genotypic resistance test is required prior to commencing the first-line highly active antiretroviral therapy (HAART).

  12. Rates and factors associated with major modifications to first-line combination antiretroviral therapy: results from the Asia-Pacific region.

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    Stephen Wright

    Full Text Available BACKGROUND: In the Asia-Pacific region many countries have adopted the WHO's public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART in resource-rich and resource-limited countries in the region. METHODS: We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD and the TREAT Asia HIV Observational Database (TAHOD. We dichotomised each country's per capita income into high/upper-middle (T-H and lower-middle/low (T-L. Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV or a substitution of two or more ARV agents from within the same ARV class. RESULTS: A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI of treatment modification was 0.48 (0.44-0.52, 0.33 (0.30-0.36 and 0.21 (0.18-0.23 for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL, quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL, monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. CONCLUSIONS: Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher

  13. [Systematic review and Meta-analysis of Shenqi Fuzheng injection combined with first-line chemotherapy for non-small cell lung cancer].

    Science.gov (United States)

    Hao, Teng-teng; Xie, Yan-ming; Liao, Xing; Wang, Jing

    2015-10-01

    The paper is to systematically evaluate the effect and safety of Shenqi Fuzheng injection (SFI) combined with first-line chemotherapy for non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) on Shenqi Fuzheng injection (SFI) combined with first-line chemotherapy (experiment group) and chemotherapy alone group ( control group) were electronically retrieved from Medline, EMbase, Clinical Trials, Cochrane Library, CBM, CNKI, VIP, and Wanfang Data base. All trials were assessed for quality according to the Cochrane Reviewer's Handbook for Systematic Reviews of Intervention and then Meta-analysis was performed withRevMan5. 2 Software. A total of 43 RCTs (3433 patients) were included after screening and selecting. Results of Meta-analysis showed that: Objective remission rate (ORR): ORR of experimental group was about 20% higher than that of control group [RR = 1.23, 95% CI (1.11,1.35), P < 0.0001]. Disease control rate (DCR):DCR of SFI combined with first-line chemotherapy was 11% higher than that of first-line chemotherapy alone [RR = 1.11, 95% CI (1.07, 1.16), P < 0.000 01]. Life quality evaluated by Kosovan performance status (KPS) showed that: life quality improvement rate of experimental group was about twice of that in control group [RR = 2.02, 95% CI (1.81, 2.26), P < 0.000 01]. Toxic and side reaction analysis showed that: the incidence of side reactions in experimental group was about 50% lower than that in control group [RR = 0.59, 95% CI (0.53, 0.66), P < 0.000 01]. Immune function test showed that: the function of experimental group was 3.2 (standard deviations) times greater than that of control group [MD = 3.23, 95% CI (2.86, 3.60), P < 0.000 01]. We can see that SFI combined with first-line chemotherapy for NSCLC can increase objective efficacy, improve life quality, decrease toxic and side reactionsinduced by chemotherapy, and improve the immune functions. As most of the included studies in this systematic evaluation had poor quality

  14. Multi-Modality Phantom Development

    Energy Technology Data Exchange (ETDEWEB)

    Huber, Jennifer S.; Peng, Qiyu; Moses, William W.

    2009-03-20

    Multi-modality imaging has an increasing role in the diagnosis and treatment of a large number of diseases, particularly if both functional and anatomical information are acquired and accurately co-registered. Hence, there is a resulting need for multi modality phantoms in order to validate image co-registration and calibrate the imaging systems. We present our PET-ultrasound phantom development, including PET and ultrasound images of a simple prostate phantom. We use agar and gelatin mixed with a radioactive solution. We also present our development of custom multi-modality phantoms that are compatible with PET, transrectal ultrasound (TRUS), MRI and CT imaging. We describe both our selection of tissue mimicking materials and phantom construction procedures. These custom PET-TRUS-CT-MRI prostate phantoms use agargelatin radioactive mixtures with additional contrast agents and preservatives. We show multi-modality images of these custom prostate phantoms, as well as discuss phantom construction alternatives. Although we are currently focused on prostate imaging, this phantom development is applicable to many multi-modality imaging applications.

  15. Conservative treatment modalities in retinoblastoma

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    Bhavna Chawla

    2013-01-01

    Full Text Available Retinoblastoma is the most common primary intraocular malignancy of childhood. A potentially curable cancer, its treatment has improved significantly over the last few decades. The purpose of this article is to review the literature on various conservative treatment modalities available for the treatment of retinoblastoma and their effectiveness, when used alone or in combination. Pubmed, Medline, Embase, and the Cochrane library were searched through 2012 for published peer reviewed data on conservative treatment modalities for retinoblastoma. Various studies show that while enucleation remains the standard of care for advanced intraocular tumors, conservative modalities that can result in globe salvage and preservation of useful vision are being increasingly employed. Such modalities include systemic chemotherapy, focal consolidation with transpupillary thermotherapy, laser photocoagulation and cryotherapy, plaque brachytherapy, and delivery of local chemotherapy using subconjunctival, sub-tenon, or intra-arterial routes. When used alone or in combination, these treatment modalities can help in avoidance of external beam radiotherapy or enucleation, thus reducing the potential for long-term side effects, while salvaging useful vision. Radioactive plaque brachytherapy has an established role in selected patients with intraocular retinoblastoma. Local injections of chemotherapeutic agents via the sub-tenon or sub-conjunctival route have been used with varying degrees of success, usually as an adjunct to systemic chemotherapy. Intra-arterial ophthalmic artery delivery of melphalan has shown promising results. It is important to recognize that today, several treatment options are available that can obviate the need for enucleation, and cure the cancer with preservation of functional vision. A thorough knowledge and understanding of these conservative treatment modalities is essential for appropriate management.

  16. Linear contextual modal type theory

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Abstract. When one implements a logical framework based on linear type theory, for example the Celf system [?], one is immediately con- fronted with questions about their equational theory and how to deal with logic variables. In this paper, we propose linear contextual modal type theory that giv...... a mathematical account of the nature of logic variables. Our type theory is conservative over intuitionistic contextual modal type theory proposed by Nanevski, Pfenning, and Pientka. Our main contributions include a mechanically checked proof of soundness and a working implementation....

  17. Diagnosis of pulmonary embolism with various imaging modalities.

    Science.gov (United States)

    Srivastava, Sunita D; Eagleton, Matthew J; Greenfield, Lazar J

    2004-06-01

    Pulmonary embolism (PE) is a major health concern that affects approximately 600,000 new patients annually. The diagnosis of PE can be difficult to make, and several imaging studies have been developed to aid in this process. Initial evaluation involves the acquisition of a chest radiograph. Findings on radiography, however, are often non-specific. The gold-standard study historically has been pulmonary angiography, with increasing diagnostic yield since the implementation of digital subtraction technology. This is an invasive procedure, however, but the incidence of major complications is low. Less invasive modalities have been developed and include ventilation-perfusion lung scans. These are used as one of the initial screening tests in evaluation of patients with suspected PE. The presence of a high-probability scan usually indicates the presence of a PE, although few patients have high probability scans. The test is significantly affected by underlying pulmonary disease or previous PE. Given this, ventilation-perfusion lung scans are limited as a primary diagnostic tool in the evaluation of suspected PE. Helical computed tomography (CT) is currently under much scrutiny as a diagnostic tool for PE. Currently a prospective, multicenter trial evaluating its efficacy (PIOPED II) has been initiated, but the results are pending. Preliminary reports suggest the helical CT and venous phase CT may become a first line study in patient evaluation. The diagnosis of PE is challenging and several imaging modalities are currently used to assist the clinician. Currently, multiple modalities are often required to make the diagnosis. With the advent of new technology and improved imaging techniques, the diagnosis of PE will become easier.

  18. A STUDY OF PEOPLE LIVING WITH HIV-AIDS [PLHA] ON FIRST LINE HIGHLY ACTIVE ANTIRETROVIRAL THERAPY [HAART] WITH IMMUNOLOGICAL FAILURE

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    Natarajan Kandasamy

    2016-07-01

    Full Text Available BACKGROUND Follow-up of patients with First line antiretroviral therapy, Cluster Differentiation (CD4 counts are done every 6 months. Viral load is not possible in resource poor settings like India. Non-Governmental Organisation (NGO’s, Human Immunodeficiency Virus (HIV treating physicians and international guidelines recommend viral load as the follow-up method for first line failure, so to study the impact of national program with immunological criteria and its sensitivity to identify virological failure is needed at this juncture. METHODS A total of 170 patients from northern districts of Tamilnadu referred to Government Hospital for Thoracic Medicine (GHTMTambaram Sanatorium State AIDS Clinical Expert Panel (SACEP committee with suspected first line ART failure were included in the study [after fulfilling the inclusion and exclusion criteria]. Viral load done for these patients were compared with Immunological criteria for concordance or discordance. RESULTS In our study we conclude that Virological discordance was noted in 51% of all cases. CD4 falling greater than 50% of on treatment peak value has the highest sensitivity to detect virological failure. The ODD’s ratio for immunological criteria CD4 falling more than 50% was three times more than other criteria with significant P-value 0.002. Immunological criteria CD4 persistently below 100 had highest specificity. CONCLUSION Immunological criteria CD4 falling more than 50% had highest sensitivity. 2. Immunological criteria CD4 persistently below 100 had had highest specificity. 3. The ODD’s ratio for immunological criteria CD4 falling more than 50% of on treatment peak value was three times more than other criteria with significant P-value 0.002. 4. Immunological and virological discordance was 51% of all cases. 5. Differences in age and duration of ART was not associated with virological failure between males and females. 6. An economical lab test with low cost to detect the viral

  19. The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa.

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    Gwenan M Knight

    Full Text Available A 4-month first-line treatment regimen for tuberculosis disease (TB is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa.An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015-2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current, reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds.It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range] per month at a willingness-to-pay threshold of one GDP per capita ($6,618.The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa.

  20. Design of a randomized trial to evaluate the influence of mobile phone reminders on adherence to first line antiretroviral treatment in South India - the HIVIND study protocol

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    Kumarasamy Nagalingeswaran

    2010-03-01

    Full Text Available Abstract Background Poor adherence to antiretroviral treatment has been a public health challenge associated with the treatment of HIV. Although different adherence-supporting interventions have been reported, their long term feasibility in low income settings remains uncertain. Thus, there is a need to explore sustainable contextual adherence aids in such settings, and to test these using rigorous scientific designs. The current ubiquity of mobile phones in many resource-constrained settings, make it a contextually appropriate and relatively low cost means of supporting adherence. In India, mobile phones have wide usage and acceptability and are potentially feasible tools for enhancing adherence to medications. This paper presents the study protocol for a trial, to evaluate the influence of mobile phone reminders on adherence to first-line antiretroviral treatment in South India. Methods/Design 600 treatment naïve patients eligible for first-line treatment as per the national antiretroviral treatment guidelines will be recruited into the trial at two clinics in South India. Patients will be randomized into control and intervention arms. The control arm will receive the standard of care; the intervention arm will receive the standard of care plus mobile phone reminders. Each reminder will take the form of an automated call and a picture message. Reminders will be delivered once a week, at a time chosen by the patient. Patients will be followed up for 24 months or till the primary outcome i.e. virological failure, is reached, whichever is earlier. Self-reported adherence is a secondary outcome. Analysis is by intention-to-treat. A cost-effectiveness study of the intervention will also be carried out. Discussion Stepping up telecommunications technology in resource-limited healthcare settings is a priority of the World Health Organization. The trial will evaluate if the use of mobile phone reminders can influence adherence to first-line

  1. More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments.

    Science.gov (United States)

    Kandolf Sekulovic, L; Peris, K; Hauschild, A; Stratigos, A; Grob, J-J; Nathan, P; Dummer, R; Forsea, A-M; Hoeller, C; Gogas, H; Demidov, L; Lebbe, C; Blank, C; Olah, J; Bastholt, L; Herceg, D; Neyns, B; Vieira, R; Hansson, J; Rutkowski, P; Krajsova, I; Bylaite-Bucinskiene, M; Zalaudek, I; Maric-Brozic, J; Babovic, N; Banjin, M; Putnik, K; Weinlich, G; Todorovic, V; Kirov, K; Ocvirk, J; Zhukavets, A; Kukushkina, M; De La Cruz Merino, L; Ymeri, A; Risteski, M; Garbe, C

    2017-04-01

    Despite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF). Web-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes. The recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Magnitude and correlates of moderate to severe anemia among adult HIV patients receiving first line HAART in Northwestern Tanzania: a cross sectional clinic based study

    Science.gov (United States)

    Gunda, Daniel Wilfred; Kilonzo, Semvua Bukheti; Mpondo, Bonaventura Cornel

    2016-01-01

    Introduction Moderate to severe anemia is an important clinical problem in HIV patients on Highly Active Antiretroviral Therapy. The rate of progression and mortality in this sub group of patients is high compared to non anemic patients. In sub Saharan Africa with scale up of Anti retroviral therapy, the magnitude of this problem is not known especially in Tanzania. This study aimed at determining the magnitude and correlates of moderate to severe anemia in HIV patients receiving first line ART in northwestern Tanzania. Methods This was a cross sectional clinic based study, involving adult HIV patients on first line Highly Active Antiretroviral Therapy at Bugando Medical Centre Care and Treatment Center. The patients’ data were analyzed using STATA version 11 to determine the prevalence of moderate to severe anemia and risk factors that could predict occurrence of anemia. Results In this study 346 patients on Highly Active Anti-Retroviral Therapy were enrolled, of whom 100(40.46%) had moderate to severe anemia. The odds of being anemic were strongly predicted by Zidovudine based regime, low baseline CD4 count (100fl. Conclusion The prevalence of moderate to severe anemia is significantly high in this cohort of HIV-infected patients on first line Anti Retroviral Therapy and it is strongly predicted by Zidovudine based regime, low baseline CD4 and HIV stage 3 and 4. On clinical grounds this suggests that patients who are initiated on Zidovudine based regimen and those in advanced HIV at enrollment should have regular haemoglobin follow up to identify anemia at its earliest stage to improve the clinical outcome of these patients. PMID:27200131

  3. Adoption of new HIV treatment guidelines and drug substitutions within first-line as a measure of quality of care in rural Lesotho: health centers and hospitals compared.

    Science.gov (United States)

    Labhardt, Niklaus D; Sello, Motlalepula; Lejone, Thabo; Ehmer, Jochen; Mokhantso, Mohlaba; Lynen, Lutgarde; Pfeiffer, Karolin

    2012-10-01

    In 2007, Lesotho launched new national antiretroviral treatment (ART) guidelines, prioritising tenofovir and zidovudine over stavudine as a backbone together with lamivudine. We compared the rate of adoption of these new guidelines and substitution of first-line drugs by health centers (HC) and hospitals in two catchment areas in rural Lesotho. Retrospective cohort analysis. Patients aged ≥16 years were stratified into a HC- and a hospital-group. Type of backbone at ART-initiation (i), substitutions within first line (ii) and type of backbone among patients retained by December 2010 (iii). A multiple logistic regression model including HC vs. hospital, patient characteristics (sex, age, WHO-stage, baseline CD4-count, concurrent pregnancy, concurrent tuberculosis treatment) and year of ART-start, was used. Of 3936 adult patients initiated on ART between 2007 and 2010, 1971 started at hospitals and 1965 at HCs. Hospitals were more likely to follow the new guidelines as measured by prescription of backbones without stavudine (Odds-ratio 1.55; 95%CI: 1.32-1.81) and had a higher rate of drug substitutions while on first-line ART (2.39; 1.83-3.13). By December 2010, patients followed at health centres were more likely to still receive stavudine (2.28; 1.83-2.84). Health centers took longer to adopt the new guidelines and substituted drugs less frequently. Decentralised ART-programmes need close support, supervision and mentoring to absorb new guidelines and to adhere to them. © 2012 Blackwell Publishing Ltd.

  4. A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naive patients starting a first-line HAART.

    Directory of Open Access Journals (Sweden)

    Daniele Armenia

    Full Text Available We previously found that a very low geno2pheno false positive rate (FPR ≤ 2% defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (% values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3 and on the time to achieve virological success (the first HIV-RNA measurement 60; p = 0.008. The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003 and to achieve virological success (0.50 [0.26-0.94], p = 0.031 than those with pre-HAART FPR >60%.Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

  5. Effectiveness and tolerance of single tablet versus once daily multiple tablet regimens as first-line antiretroviral therapy - Results from a large french multicenter cohort study

    Science.gov (United States)

    Cotte, Laurent; Ferry, Tristan; Pugliese, Pascal; Valantin, Marc-Antoine; Allavena, Clotilde; Cabié, André; Poizot-Martin, Isabelle; Rey, David; Duvivier, Claudine; Cheret, Antoine; Dellamonica, Pierre; Pradat, Pierre; Parienti, Jean-Jacques

    2017-01-01

    Objectives Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART. Methods Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat’AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM). Results Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, pPSM cohort (HR = 0.55, pPSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, pPSM cohort (HR = 1.22, p = 0.11). Conclusion First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar. PMID:28152047

  6. Validation and implementation of array comparative genomic hybridisation as a first line test in place of postnatal karyotyping for genome imbalance

    Directory of Open Access Journals (Sweden)

    Docherty Zoe

    2010-04-01

    Full Text Available Abstract Background Several studies have demonstrated that array comparative genomic hybridisation (CGH for genome-wide imbalance provides a substantial increase in diagnostic yield for patients traditionally referred for karyotyping by G-banded chromosome analysis. The purpose of this study was to demonstrate the feasibility of and strategies for, the use of array CGH in place of karyotyping for genome imbalance, and to report on the results of the implementation of this approach. Results Following a validation period, an oligoarray platform was chosen. In order to minimise costs and increase efficiency, a patient/patient hybridisation strategy was used, and analysis criteria were set to optimise detection of pathogenic imbalance. A customised database application with direct links to a number of online resources was developed to allow efficient management and tracking of patient samples and facilitate interpretation of results. Following introduction into our routine diagnostic service for patients with suspected genome imbalance, array CGH as a follow-on test for patients with normal karyotypes (n = 1245 and as a first-line test (n = 1169 gave imbalance detection rates of 26% and 22% respectively (excluding common, benign variants. At least 89% of the abnormalities detected by first line testing would not have been detected by standard karyotype analysis. The average reporting time for first-line tests was 25 days from receipt of sample. Conclusions Array CGH can be used in a diagnostic service setting in place of G-banded chromosome analysis, providing a more comprehensive and objective test for patients with suspected genome imbalance. The increase in consumable costs can be minimised by employing appropriate hybridisation strategies; the use of robotics and a customised database application to process multiple samples reduces staffing costs and streamlines analysis, interpretation and reporting of results. Array CGH provides a

  7. Survival times of women with metastatic breast cancer starting first-line chemotherapy in routine clinical practice versus contemporary randomised trials.

    Science.gov (United States)

    Thientosapol, E S; Tran, T T; Della-Fiorentina, S A; Adams, D H; Chantrill, L; Stockler, M R; Kiely, B E

    2013-08-01

    Survival times of women starting first-line chemotherapy for metastatic breast cancer (MBC) in routine clinical practice were determined and compared with those from a systematic review of randomised clinical trials. We identified women with MBC starting first-line chemotherapy from June 2003 to February 2011 and recorded their demographics, tumour and treatment characteristics, and survival times from the start of chemotherapy. Their survival distribution was summarised by the following percentiles (represented scenarios for survival): 90th (worst-case), 75th (lower-typical), 25th (upper-typical) and 10th (best-case), which were compared with the same percentiles from our systematic review of first-line chemotherapy trials. The 273 women had a median age of 56 years, and a median time from diagnosis of MBC of 3 months. Eastern Cooperative Oncology Group performance status was 0-1 in 80%. Tumours were hormone receptor positive in 69%, human epidermal growth factor receptor 2 (HER2)-positive in 27% and triple negative in 13%. Survival times in months in routine clinical practice (vs the systematic review) were: 90th percentile 4 (6); 75th percentile 9 (12); median 20 (22); 25th percentile 36 (36) and 10th percentile 61 (56). Independent predictors of overall survival included HER2-positive disease (hazard ratio (HR) 0.49, P = 0.0002), hormone receptor positive disease (HR 0.51, P = 0.0004), Eastern Cooperative Oncology Group performance status 0-1 (HR 0.36, P HR 1.86, P = 0.0002). Median and better survival times in routine practice were similar to those from randomised clinical trials; however, survival times worse than the median were shorter, likely reflecting patient selection in trials. Oncologists should adjust trial-based survival estimates for patients not meeting typical trial eligibility criteria. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  8. Clinical Study of Pemetrexed as the First-line Treatment in Elderly Patients with Advanced Non-squamous Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaolin Pu

    2013-12-01

    Full Text Available Objective: To evaluate the efficacy and adverse reactions of pemetrexed as the first-line treatment in elderly patients with advanced non-squamous non-small-cell lung cancer (NSCLC. Methods: The elderly patients with advanced non-squamous NSCLC received pemetrexed as the first-line treatment were retrospectively analyzed. All of them were intravenously injected 500 mg/ m2 pemetrexed, and 21 days were as one cycle. The efficiency was evaluated every two cycles till the disease progressed or sever adverse reactions occurred. The condition of adverse reactions as well as final outcome were observed. Results: Eighty-seven patients were enrolled in the research, totally receiving 392 cycles of chemotherapy, and the mean for 1 patient being 4.5 cycles. After 2 cycles of chemotherapy, partial response (PR and stable disease (SD were respectively 39 and 18 cases. The response rate and disease control rate were 44.8% and 65.5%, respectively. The median overall survival (OS of all patients was 16.1 months, and median progression-free survival (PFS was 3.2 months. Twenty-five patients completed 4 cycles of chemotherapy, and 32 patients completed 6 cycles of chemotherapy at least. The median OS of patients > 4 cycles of chemotherapy was 17.4 months, while those ≤ 4 cycles was 13.6 months, and the difference had statistical significance (χ2 = 4.374, P = 0.036. The major adverse reactions included myelosuppression, fatigue and gastrointestinal reactions, mainly at grades 1 - 2. No treatment-related deaths occurred. Conclusion: The efficiency of pemetrexed is definite as the first-line treatment in elderly patients with advanced non-squamous NSCLC, and the incidence of adverse reactions is low. The prognosis of patients is associated with cycles of pemetrexed chemotherapy.

  9. High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Rasmussen, Mads H; Jensen, Niels F; Tarpgaard, Line S; Qvortrup, Camilla; Rømer, Maria U; Stenvang, Jan; Hansen, Tine P; Christensen, Lise L; Lindebjerg, Jan; Hansen, Flemming; Jensen, Benny V; Hansen, Torben F; Pfeiffer, Per; Brünner, Nils; Ørntoft, Torben F; Andersen, Claus L

    2013-06-01

    The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major unsolved problem is that no predictors of response to these treatments are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among others, high expression of miR-625-3p, miR-181b and miR-27b to be associated with poor clinical response. In a validation cohort of 94 mCRC patients treated first-line with XELOX, high expression of miR-625-3p was confirmed to be associated with poor response (OR = 6.25, 95%CI [1.8; 21.0]). Independent analyses showed that miR-625-3p was not dysregulated between normal and cancer samples, nor was its expression associated with recurrence of stage II or III disease, indicating that miR-625-3p solely is a response marker. Finally, we also found that these miRNAs were up-regulated in oxaliplatin resistant HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) colon cancer cell lines as compared with their isogenic parental cells. Altogether, our results suggest an association between miR-625-3p and response to first-line oxaliplatin based chemotherapy of mCRC.

  10. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  11. Rapid, automated, nonradiometric susceptibility testing of Mycobacterium tuberculosis complex to four first-line antituberculous drugs used in standard short-course chemotherapy

    DEFF Research Database (Denmark)

    Johansen, Isik Somuncu; Thomsen, Vibeke Østergaard; Marjamäki, Merja

    2004-01-01

    The increasing prevalence of drug-resistant tuberculosis necessitates rapid and accurate susceptibility testing. The nonradiometric BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT) system for susceptibility testing was evaluated on 222 clinical Mycobacterium tuberculosis complex isolates...... MGIT system is a rapid and reliable alternative for susceptibility testing of M. tuberculosis complex to first-line drugs....... for isoniazid, rifampin, and ethambutol. Fifty-seven of the isolates were tested for pyrazinamide. Results were compared to those of radiometric BACTEC 460 system and discrepancies were resolved by the agar proportion method. We found an overall agreement of 99.0% for isoniazid, 99.5% for rifampin, 98...

  12. Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique

    DEFF Research Database (Denmark)

    Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima

    2008-01-01

    BACKGROUND: In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin...... investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the Plasmodium falciparum genes Pfdhfr, Pfdhps and Pfcrt before and a year after the introduction of SP. METHODS: Samples were collected during two cross sectional surveys in early 2002 and 2003...

  13. Comparison of therapeutic effects between EGFR-TKI in first-line and second-line therapy in non-small cell lung cancer (NSCLC) patients

    OpenAIRE

    CHEN, LIANG-AN

    2011-01-01

    Platinum-based chemotherapy is still the standard first-line treatment for patients with advanced non-small cell lung cancer(NSCLC).Molecular targeted agents provide a new option for NSCLC patients.Clinical trial had shown that survival rate with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI) treatment was not inferior compared with platinum-based chemotherapy in second line NSCLC therapy.However,for the patients with EGFR gene mutation,a better outcome has been achieved...

  14. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

    DEFF Research Database (Denmark)

    Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

    2016-01-01

    BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International m......RCC Database Consortium (IMDC) to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS (OS2) and second-line PFS (PFS2) were also evaluated. RESULTS: We obtained data from 7438...

  15. Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

    Science.gov (United States)

    Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

    2016-08-01

    Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

  16. GEMCYTABIN (CYTOGEM®) AND CISPLATIN AS FIRST-LINE THERAPY FOR ADVANCED BLADDER CANCER: RESULTS OF A PROSPECTIVE OPEN-LABELED NON-COMPARATIVE NON-RANDOMIZED STUDY

    OpenAIRE

    V. B. Matveev; M. I. Volkova; M. M. Konstantinova; L. V. Schapligin; G. M. Manikhas

    2014-01-01

    Purpose.  The primary end-points of the study were overall response rate, progressive-free and overall survival in patients received Gemcytabin (Cytogem®) and Cisplatin as first-line therapy for transitional-cell bladder cancer. Secondary end-points were toxicity and safty of the regimen. Material. From February 2005 to March 2007 25 patients with morphologically verified inoperable locally advanced and metastatic transitional-cell bladder cancer were recruited. Men-to-women ratio was 3:1. Me...

  17. Epidermal Growth Factor-like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Nielsen, Boye Schnack; Sørensen, Flemming Brandt

    2014-01-01

    with bevacizumab, in patients with metastatic colorectal cancer (mCRC). A total of 158 patients from two different, but comparable, cohorts were included. Analyses were performed on tumor tissue from the primary tumor either based on a whole-tumor resection or an endoscopic biopsy. EGFL7 was analyzed...... = 0.049). The results showed no significant relationship between the miR126 VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC and supports the mechanism of a dual blocking of the vascular endothelial...

  18. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study

    DEFF Research Database (Denmark)

    Andersson, Michael; Lidbrink, Elisabeth; Bjerre, Karsten;

    2011-01-01

    To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer.......To evaluate docetaxel or vinorelbine, both with trastuzumab, as first-line therapy of human epidermal growth factor receptor 2-positive advanced breast cancer....

  19. Wavefront reconstruction by modal decomposition

    CSIR Research Space (South Africa)

    Schulze, C

    2012-08-01

    Full Text Available We propose a new method to determine the wavefront of a laser beam based on modal decomposition by computer-generated holograms. The hologram is encoded with a transmission function suitable for measuring the amplitudes and phases of the modes...

  20. Arithmetic Memory Is Modality Specific.

    Directory of Open Access Journals (Sweden)

    Timothy Myers

    Full Text Available In regards to numerical cognition and working memory, it is an open question as to whether numbers are stored into and retrieved from a central abstract representation or from separate notation-specific representations. This study seeks to help answer this by utilizing the numeral modality effect (NME in three experiments to explore how numbers are processed by the human brain. The participants were presented with numbers (1-9 as either Arabic digits or written number words (Arabic digits and dot matrices in Experiment 2 at the first (S1 and second (S2 stimuli. The participant's task was to add the first two stimuli together and verify whether the answer (S3, presented simultaneously with S2, was correct. We hypothesized that if reaction time (RT at S2/S3 depends on the modality of S1 then numbers are retrieved from modality specific memory stores. Indeed, RT depended on the modality of S1 whenever S2 was an Arabic digit which argues against the concept of numbers being stored and retrieved from a central, abstract representation.

  1. Clinical usefulness of 18F-FDG PET/CT in the restaging of esophageal cancer after surgical resection and radiotherapy

    Institute of Scientific and Technical Information of China (English)

    Long Sun; Xin-Hui Su; Yong-Song Guan; Wei-Ming Pan; Zuo-Ming Luo; Ji-Hong Wei; Long Zhao; Hua Wu

    2009-01-01

    %. CONCLUSION: Selec t ive TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.

  2. Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2012-08-01

    Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

  3. Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? Yes, they continue to serve us well!

    Science.gov (United States)

    Abrahamson, Martin J

    2015-01-01

    Since their introduction to clinical practice in the 1950s, sulfonylureas have been widely prescribed for use in patients with type 2 diabetes. Of all the other medications currently available for clinical use, only metformin has been used more frequently. However, several new drug classes have emerged that are reported to have equal glucose-lowering efficacy and greater safety when added to treatment of patients in whom metformin monotherapy is no longer sufficient. Moreover, current arguments also suggest that the alternative drugs may be superior to sulfonylureas with regard to the risk of cardiovascular complications. Thus, while there is universal agreement that metformin should remain the first-line pharmacologic therapy for those in whom lifestyle modification is insufficient to control hyperglycemia, there is no consensus as to which drug should be added to metformin. Therefore, given the current controversy, we provide a Point-Counterpoint on this issue. In the point narrative presented below, Dr. Abrahamson provides his argument suggesting that avoiding use of sulfonylureas as a class of medication as an add-on to metformin is not appropriate as there are many patients whose glycemic control would improve with use of these drugs with minimal risk of adverse events. In the following counterpoint narrative, Dr. Genuth suggests there is no longer a need for sulfonylureas to remain a first-line addition to metformin for those patients whose clinical characteristics are appropriate and whose health insurance and/or financial resources make an alternative drug affordable.

  4. Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? No, it's time to move on!

    Science.gov (United States)

    Genuth, Saul

    2015-01-01

    Since their introduction to clinical practice in the 1950s, sulfonylureas have been widely prescribed for use in patients with type 2 diabetes. Of all the other medications currently available for clinical use, only metformin has been used more frequently. However, several new drug classes have emerged that are reported to have equal glucose-lowering efficacy and greater safety when added to treatment of patients in whom metformin monotherapy is no longer sufficient. Moreover, current arguments also suggest that the alternative drugs may be superior to sulfonylureas with regard to the risk of cardiovascular complications. Thus, while there is universal agreement that metformin should remain the first-line pharmacologic therapy for those in whom lifestyle modification is insufficient to control hyperglycemia, there is no consensus as to which drug should be added to metformin. Therefore, given the current controversy, we provide a Point-Counterpoint on this issue. In the preceding point narrative, Dr. Abrahamson provides his argument suggesting that avoiding use of sulfonylureas as a class of medication as an add-on to metformin is not appropriate as there are many patients whose glycemic control would improve with use of these drugs with minimal risk of adverse events. In the counterpoint narrative below, Dr. Genuth suggests there is no longer a need for sulfonylureas to remain a first-line addition to metformin for those patients whose clinical characteristics are appropriate and whose health insurance and/or financial resources make an alternative drug affordable.

  5. Afatinib in first-line setting for NSCLC harbouring common EGFR mutations: new light after the preliminary results of LUX-Lung 7?

    Science.gov (United States)

    Passaro, Antonio; Pochesci, Alessia; Spitaleri, Gianluca; Catania, Chiara; Noberasco, Cristina; Del Signore, Ester; de Marinis, Filippo

    2016-03-01

    The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed dramatically the history of non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Several randomized prospective trials confirmed the superiority of these target agents about survival and response rate when comparing with platinum-based chemotherapy. Knowledge about EGFR mutations increased gradually during the development of target agents and different clinical trials. EGFR mutations cannot be considered all equal, but different entities should be considered in our clinical practice: exon 19 deletions, exon 21 mutation (L858R) and uncommon mutation (exon 20, exon 18 and double mutation). Nowadays, we dispose of three different EGFR TKIs (afatinib, erlotinib and gefitinib) approved for the treatment for first-line treatment of patients di NSCLC carrying EGFR, that was compared only by indirect analysis, producing data not always clear and convincing. This research highlight is an overview of data about EGFR TKIs in first-line setting, focusing on differences about exon 19 deletions and L585R mutation in patients treated with different TKIs. In addition, we report the preliminary results of the first head-to-head randomized clinical trial between two different EGFR TKIs, the LUX-Lung 7 (LL7) that compared afatinib and gefitinib showing interesting results.

  6. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia.

    Science.gov (United States)

    Eichhorst, Barbara F; Busch, Raymonde; Stilgenbauer, Stephan; Stauch, Martina; Bergmann, Manuela A; Ritgen, Matthias; Kranzhöfer, Nicole; Rohrberg, Robert; Söling, Ulrike; Burkhard, Oswald; Westermann, Anne; Goede, Valentin; Schweighofer, Carmen D; Fischer, Kirsten; Fink, Anna-Maria; Wendtner, Clemens M; Brittinger, Günter; Döhner, Hartmut; Emmerich, Bertold; Hallek, Michael

    2009-10-15

    Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m(2) for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with www.isrctn.org under identifier ISRCTN 36294212.

  7. How do patients who fail first-line TB treatment but who are not placed on an MDR-TB regimen fare in South India?

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    Sharath Burugina Nagaraja

    Full Text Available SETTING: Seven districts in Andhra Pradesh, South India. OBJECTIVES: To a determine treatment outcomes of patients who fail first line anti-TB treatment and are not placed on an multi-drug resistant TB (MDR-TB regimen, and b relate the treatment outcomes to culture and drug susceptibility patterns (C&DST. DESIGN: Retrospective cohort study using routine programme data and Mycobacterium TB Culture C&DST between July 2008 and December 2009. RESULTS: There were 202 individuals given a re-treatment regimen and included in the study. Overall treatment outcomes were: 68 (34% with treatment success, 84 (42% failed, 36 (18% died, 13 (6.5% defaulted and 1 transferred out. Treatment success for category I and II failures was low at 37%. In those with positive cultures, 81 had pan-sensitive strains with 31 (38% showing treatment success, while 61 had drug-resistance strains with 9 (15% showing treatment success. In 58 patients with negative cultures, 28 (48% showed treatment success. CONCLUSION: Treatment outcomes of patients who fail a first-line anti-TB treatment and who are not placed on an MDR-TB regimen are unacceptably poor. The worst outcomes are seen among category II failures and those with negative cultures or drug-resistance. There are important programmatic implications which need to be addressed.

  8. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20-1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59-0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46-2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis.

  9. Three Weekly Irinotecan and Bolus 5-Fluorouracil Combination in the First Line Treatment of Advanced Gastric Cancer - A Single Institution Experience

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    Mohamed Mesmoudi

    2016-06-01

    Full Text Available Background: The goal of this study is to determine the efficacy and toxicity of a non-platinum based chemotherapy combination using irinotecan associated to bolus 5-FU as first line treatment in advanced gastric cancer. Materiel and methods: Retrospective analysis of a population of patients treated for metastatic and locally advanced gastric cancer with irinotecan and 5-FU as upfront chemotherapy. Results: Thirteen patients were enrolled. The median age was 56 years. Seven patients were males and six were of females. Ten patients had a metastatic disease and three patients had a locally advanced disease. Patients received a total number of 43 cycles of chemotherapy. Overall response rate was 38,4%, median time to progression (TTP was 3 months, and median overall survival was 4 months. Three patients (23,1% presented grade 3 /4 neutropenia complicated with an infectious episode with fever in two cases, three patients (23,1% required blood transfusion for a grade 4 anemia, and one patient (7,6% was hospitalized for a severe episode of diarrhea. Conclusion: Three weekly irinotecan and bolus 5-FU is an interesting combination as first line treatment of advanced gastric cancer; designed clinical trials are needed to confirm the activity of this combination.

  10. Caspofungin first-line therapy for invasive aspergillosis in allogeneic hematopoietic stem cell transplant patients: an European Organisation for Research and Treatment of Cancer study.

    Science.gov (United States)

    Herbrecht, R; Maertens, J; Baila, L; Aoun, M; Heinz, W; Martino, R; Schwartz, S; Ullmann, A J; Meert, L; Paesmans, M; Marchetti, O; Akan, H; Ameye, L; Shivaprakash, M; Viscoli, C

    2010-07-01

    Caspofungin at standard dose was evaluated as first-line monotherapy of mycologically documented probable/proven invasive aspergillosis (IA) (unmodified European Organisation for Research and Treatment of Cancer/Mycosis Study Group criteria) in allogeneic hematopoietic SCT patients. The primary efficacy end point was complete or partial response at end of caspofungin treatment. Response at week 12, survival and safety were additional end points. Enrollment was stopped prematurely because of low accrual, with 42 enrolled and 24 eligible, giving the study a power of 85%. Transplant was from unrelated donors in 16 patients; acute or chronic GVHD was present in 15. In all, 12 patients were neutropenic (<500/microl) at baseline, 10 received steroids and 16 calcineurin inhibitors or sirolimus. Median duration of caspofungin treatment was 24 days. At the end of caspofungin therapy, 10 (42%) patients had complete or partial response (95% confidence interval: 22-63%); 1 (4%) and 12 (50%) had stable and progressing disease, respectively; one was not evaluable. At week 12, eight patients (33%) had complete or partial response. Survival rates at week 6 and 12 were 79 and 50%, respectively. No patient had a drug-related serious adverse event or discontinued because of toxicity. Caspofungin first-line therapy was effective and well tolerated in allogeneic hematopoietic SCT patients with mycologically documented IA.

  11. Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC

    Science.gov (United States)

    Perrone, Francesco; Baldassarre, Gustavo; Indraccolo, Stefano; Signoriello, Simona; Chiappetta, Gennaro; Esposito, Franca; Ferrandina, Gabriella; Franco, Renato; Mezzanzanica, Delia; Sonego, Maura; Zulato, Elisabetta; Zannoni, Gian F.; Canzonieri, Vincenzo; Scambia, Giovanni; Sorio, Roberto; Savarese, Antonella; Breda, Enrico; Scollo, Paolo; Ferro, Antonella; Tamberi, Stefano; Febbraro, Antonio; Natale, Donato; Maio, Massimo Di; Califano, Daniela; Scognamiglio, Giosuè; Lorusso, Domenica; Canevari, Silvana; Losito, Simona; Gallo, Ciro; Pignata, Sandro

    2016-01-01

    Background No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m², every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m², every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model. Results After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. Conclusion These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted. PMID:27655643

  12. Efficacy and Safety of the Triple Therapy Containing Ilaprazole, Levofloxacin, and Amoxicillin as First-Line Treatment in Helicobacter pylori Infections

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    Hyo Jun Ahn

    2017-01-01

    Full Text Available Background and Aims. To establish the efficacy and safety of ilaprazole, levofloxacin, and amoxicillin as a first-line eradication treatment for Helicobacter pylori. Methods. Patients with gastric ulcer, duodenal ulcer, or gastritis, as detected by esophagogastroduodenoscopy with confirmed H. pylori infection between September 2014 and November 2015, were enrolled in the study. All participants received ilaprazole (10 mg bid, levofloxacin (500 mg bid, and amoxicillin (1000 mg bid for 10 days. H. pylori eradication was confirmed by a 13C-urea breath test at 6–8 weeks after the end of treatment. Results. Of 84 patients included in the analysis, the eradication rate was 88.8% in the per protocol group (n=80. Demographic factors such as age, gender, body mass index (BMI, alcohol, smoking, hypertension, diabetes mellitus, and peptic ulcer did not affect the eradication rate. However, multivariate analysis showed that overweight patients and patients with cerebrovascular accident (CVA had a significantly lower eradication rate than patients with normal BMI and without CVA. Laboratory test results did not change significantly after treatment. A total of six (7.5% patients developed eight adverse reactions. Conclusions. A 10-day triple therapy containing ilaprazole, levofloxacin, and amoxicillin is a safe alternative first-line eradication treatment for H. pylori.

  13. First-Line Treatment of Metastatic Pancreatic Adenocarcinoma: Can We Do Better? Highlights from the "2010 ASCO Annual Meeting'. Chicago, IL, USA. June 4-8, 2010

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    Man Yee Merl

    2010-07-01

    Full Text Available Pancreatic cancer is one of the most devastating solid tumor malignancies. Majority of patients have metastatic disease upon diagnosis. Five-year survival is less than 5% for all stages of pancreatic cancer combined. Gemcitabine has been the standard palliative therapy for advanced pancreatic cancer over the past decade. Many studies attempted to develop combination regimens, but they failed to improve overall survival in the metastatic settings. The combination of gemcitabine and erlotinib was the first combination regimen to show improvements in survival benefit compared with gemcitabine alone and became the first-line combination therapy in advanced pancreatic cancer. The search for better treatment strategies to prolong survival in this deadly disease is very much needed and is a worldwide effort. There were many studies presented at the 2010 American Society of Clinical Oncology (ASCO Annual Meeting focused on first-line therapy in metastatic pancreatic cancer. This article highlights a few phase III and II studies that have demonstrated encouraging results.

  14. Adverse Events of Afatinib as First-line Treatment for Five Cases of Advanced
Lung Adenocarcinoma and Review of Literature

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    Hong TAO

    2014-04-01

    Full Text Available Background and objective Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR mutations. The aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. Methods Patients with lung adenocarcinoma (stage IIIb or IV with EGFR mutations were first-line treated with an oral administration of afatinib (40 mg/d until disease progression. Adverse events, effects, and survival condition were observed. Results The most common adverse events were diarrhea (n=5, 100%, skin rash (n=4, 80%, and mucositis/stomatitis (n=4, 80%. Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. Three patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%, one with stable disease (25% and one with progressive disease (25%. Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. Conclusion Afatinib was approved as first-line treatment for patients with advanced lung adenocarcinoma. The most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for confirmation.

  15. ON THE REDUNDANCY OF COMPLEX MODAL PARAMETERS

    Institute of Scientific and Technical Information of China (English)

    陈奎孚; 焦群英

    2004-01-01

    Generating the simulation transfer function (TF) is indispensable to modal analysis, such as examining modal parameters identification algorithm, and assessing modal analysis software. Comparing 3 feasible algorithms to simulate TF shows that, one of them is preperable, which is expressing the TF as the function of the complex modal parameters ( CMPs ) , because the deliberate behaviors of CMPs can be implemented easily,such as, dense modals , large damping, and complex modal shape, etc. Nonetheless, even this preferable algorithms is elected, the complex modal shapes cannot be specified arbitrarily, because the number of CMPs far more exceeds that in physical coordinate. So for physical realizable system, there are redundant constraints in CMPs. By analyzing the eigenvalue problem of a complex modal system, and the inversion equations from CMPs to physical parameters, the explicit redundancy constraints were presented. For the special cases, such as the real modal, the damping free modal, and non-complete identification, the specific forms of the redundancy constraints were discussed, along with the number of independent parameters. It is worthy of noting that, redundancy constraints are automatically satisfied for the real modal case. Their equivalent forms on the transfer matrix and a column of transfer matrix were also provided. These results are applicable to generate TF, to implement identification by optimization and appreciate the identification results, to evaluate residual modal, and to verify the complementary of identified modal orders.

  16. Modal liquid crystal wavefront corrector.

    Science.gov (United States)

    Kotova, S; Kvashnin, M; Rakhmatulin, M; Zayakin, O; Guralnik, I; Klimov, N; Clark, P; Love, Gordon; Naumov, A; Saunter, C; Loktev, M; Vdovin, G; Toporkova, L

    2002-11-04

    Results are presented of the properties of a liquid crystal wavefront corrector for adaptive optics. The device is controlled using modal addressing in which case the device behaves more like a continuous facesheet deformable mirror than a segmented one. Furthermore, the width and shape of the influence functions are electrically controllable. We describe the construction of the device, the optical properties, and we show experimental results of low order aberration generation.

  17. Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy: A Systematic Review and Meta-Analysis

    Institute of Scientific and Technical Information of China (English)

    Yuan-Rong Ren; Yong-Dong Jin; Zhi-Hui Zhang; Li Li; Ping Wu

    2015-01-01

    Background:Rituximab in combination with cyclophosphamide,doxorubicin,vincristine,and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL).But relapse and refractory DLBCL occur frequently.Although rituximab is effective,its role in salvage therapy after autologous transplant remains unclear.Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit.This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.Methods:We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation.We searched the Cochrane Library,PubMed,EMBASE,conference proceedings,databases of ongoing trials,and references of published trials.Two reviewers independently assessed the quality of the trials and extracted data.Hazard ratios for time-to-event data were estimated and pooled.Results:Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis.Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm,but there was no statistical significance.Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death =0.72,95% CI (0.55-0.94),P=0.02],progression-free survival (PFS) [HR =0.61,95% CI (0.52-0.72),P< 0.05],odds ratio (OR) [RR =1.26,95% CI (1.07-1.47),P =0.004] than patients in the observation arm.The rate of infection-related adverse events was higher with rituximab treatment [RR =1.37,95% CI =(1.14-1.65) P =0.001].Conclusions:After first-line chemotherapy,the two rituximab

  18. Bevacizumab plus interferon-α versus sunitinib for first-line treatment of renal cell carcinoma in Italy: a cost-minimization analysis.

    Science.gov (United States)

    Ravasio, Roberto; Ortega, Cinzia; Sabbatini, Roberto; Porta, Camillo

    2011-01-01

    Renal cell carcinoma (RCC) is the most common form of kidney cancer. Immunotherapy with interferon-α (IFNα) and interleukin-2 (IL-2) has been the historical therapy of choice for the treatment of locally advanced or metastatic RCC prior to the more recent development of targeted therapies, including sunitinib and bevacizumab (combined with IFNα). Clinically and statistically significant advantages have been shown with both sunitinib and the combination of bevacizumab + IFNα versus IFNα alone in the treatment of advanced or metastatic RCC. The present study evaluated the incremental costs of bevacizumab + IFNα versus sunitinib for the first-line treatment of advanced or metastatic RCC assuming similar efficacy for these treatments. The efficacy profiles of bevacizumab + IFNα or sunitinib alone have been shown (indirectly) to be similar in patients with RCC; indeed, median progression-free survival (PFS) with either treatment is in the 10- to 11-month range. Therefore, a cost-minimization analysis was performed, focusing on direct medical costs only (drugs, administration and management of adverse events). The analysis considered the perspective of the Italian National Health Service (NHS), comparing the cost of bevacizumab (10 mg/kg) plus IFNα (9, 6 or 3 million IU [MIU]) versus sunitinib (50 mg) as first-line therapies for advanced or metastatic clear-cell RCC. The average cost per treated patient (year 2010 values) was assessed for the two treatment options at 11 months (median PFS). Assuming a PFS of 11 months for both treatment options, bevacizumab + IFNα (9 MIU) would be a lower cost strategy (cost savings of €2052 per patient) than sunitinib. This difference arises mainly from the reduction in the acquisition cost of bevacizumab to the NHS (risk-sharing agreement). The cost advantages for bevacizumab would increase in parallel with a reduction in IFNα dosing; for example, with IFNα 6 MIU the corresponding cost savings would be

  19. Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    LIANG Xiao-bo; HOU Sheng-huai; Li Yao-ping; WANG Li-chun; ZHANG Xin; YANG Jun

    2010-01-01

    Background To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fiuorouracil and leucovorin as first-line therapy for advanced colorectal cancer.Methods Literature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2.Results According to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group.The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR)=0.82, 95% confidence interval (95%CI) (0.70, 0.96), P=0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P=0.008). In the comparison of grade 3-4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR=1.94, 95%CI(1.22, 3.09), P=0.005; 1.71, 95%CI (1.34, 2.18), P <0.001; 14.56, 95%CI (4.11,51.66), P <0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR=0.06, 95%CI(0.03, 0.14), P <0.00001; 0.70, 95%CI(0.55, 0.91), P=0.006; 0.18, 95%CI(0.05, 0.61), P=0.006), respectively.Conclusions Both irinotecan and oxaliplatin combined

  20. Cost effectiveness analysis of fesoterodine compared to mirabegron in first-line therapy setting for overactive bladder with urge urinary incontinence, from the Spanish National Health System perspective.

    Science.gov (United States)

    Angulo, J C; Sánchez-Ballester, F; Peral, C; Rejas, J; Ramos, J; Snedecor, S J; Sudharshan, L; Liu, S; Luo, X

    2016-10-01

    To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective. A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015. At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold. Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain. Copyright © 2016 AEU. Publicado por Elsevier España, S

  1. 125I brachytherapy of locally advanced non-small-cell lung cancer after one cycle of first-line chemotherapy:a comparison with best supportive care

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    Song J

    2017-03-01

    Full Text Available Jingjing Song* Xiaoxi Fan* Zhongwei Zhao* Minjiang Chen* Weiqian Chen, Fazong Wu, Dengke Zhang, Li Chen, Jianfei Tu, Jiansong Ji Department of Interventional Radiology, Zhejiang University Lishui Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, People’s Republic of China *These authors have contributed equally to this work Objectives: The objective of this study was to assess the efficacy of computed tomography (CT-guided 125I brachytherapy alone in improving the survival and quality of life of patients with unresectable locally advanced non-small-cell lung cancer (NSCLC after one cycle of first-line chemotherapy.Patients and methods: Sixteen patients with locally advanced NSCLC were treated with CT-guided 125I brachytherapy after one cycle of first-line chemotherapy (group A. Sixteen patients who received only best supportive care (group B were matched up with the patients in group A. Primary end point included survival, and secondary end point included assessment of safety, effectiveness of CT-guided 125I brachytherapy, and improvement in the quality of life.Results: The two groups were well balanced in terms of age, disease histology, tumor stage, tumor location, and performance status (P>0.05. The median follow-up time was 16 months (range, 3–30. The total tumor response rate was 75.0% in group A, which was significantly higher than that in group B (0.0% (P<0.01. The median progression-free survival time was 4.80 months for patients in group A and 1.35 months for patients in group B (P<0.001. Kaplan–Meier survival analysis showed that the median survival time of group A was 9.4±0.3 months versus 8.4±0.1 months in group B (P=0.013. Tumor-related symptoms of patients were significantly relieved, and the quality of life was markedly improved in group A than in group B.Conclusion: CT-guided 125I brachytherapy improved the survival of patients with locally advanced

  2. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

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    Xiao HQ

    2016-03-01

    Full Text Available Huai-Qing Xiao,1 Rong-Hua Tian,2 Zhi-Hao Zhang,1 Kai-Qi Du,1 Yi-Ming Ni3 1Department of Cardiothoracic Surgery, Zhejiang Corps Hospital, Chinese People’s Armed Police Force, Jiaxing, Zhejiang Province, People’s Republic of China; 2Department of Respiratory, Affiliated Haian People’s Hospital of Nantong University, Haian, Jiangsu, People’s Republic of China; 3Department of Cardiothoracic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Purpose: To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC through a trial-level meta-analysis. Methods: Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library. All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR, progression-free survival (PFS, and overall survival (OS were extracted and analyzed using comprehensive meta-analysis software (version 2.0. Results: A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%, with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01 but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084 in advanced nonsquamous NSCLC patients. Conclusion: Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our

  3. Trends of Mycobacterium bovis Isolation and First-Line Anti-tuberculosis Drug Susceptibility Profile: A Fifteen-Year Laboratory-Based Surveillance.

    Directory of Open Access Journals (Sweden)

    Miriam Bobadilla-del Valle

    2015-09-01

    Full Text Available Mycobacterium tuberculosis causes the majority of tuberculosis (TB cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. We describe the trends of M. bovis isolation from human samples and first-line drug susceptibility during a 15-year period in a referral laboratory located in a tertiary care hospital in Mexico City.Data on mycobacterial isolates from human clinical samples were retrieved from the laboratory's database for the 2000-2014 period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin (STR and ethambutol was determined. We identified 1,165 isolates, 73.7% were M. tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis. The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to 28.4% in 2014 (X(2trend, p<0.001. Primary STR resistance was higher among M. bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001. Secondary multidrug resistance (MDR rates were 38.5% and 34.4% for M. bovis and M. tuberculosis, respectively (p = 0.637. A rising trend of primary STR monoresistance was observed for both species (3.4% in 2000-2004 vs. 7.6% in 2010-2014; p = 0.02.There is a high prevalence and a rising trend of M. bovis isolates in our region. The proportion of pulmonary M. bovis isolates is higher than in previous reports. Additionally, we report high rates of primary anti-tuberculosis resistance and secondary MDR in both M. tuberculosis and M. bovis. This is one of the largest reports on drug susceptibility of M. bovis from human samples and shows a significant proportion of first-line anti-tuberculosis drug resistance.

  4. Treatment discontinuation in HIV-1-infected individuals starting their first-line HAART after 2008: data from the ICONA Foundation Study Cohort

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    Antonio Di Biagio

    2014-11-01

    Full Text Available Introduction: The aim of this study was to analyze the likelihood and the predictors of discontinuation of first-line regimen in the late HAART era. Methodology: An observational multi-center analysis of HIV-positive patients enrolled in ICONA. Patients eligible were those starting a first-line HAART after 1 January 2008. Discontinuation was defined as stop and/or switch of at least one drug of the regimen. All causes of discontinuation, as reported by the treating physician, were evaluated and cumulative risk of stopping was investigated according to age, gender, co-morbidity, years since starting HAART, immuno-virological status, third drug and backbone of the first regimen. Kaplan Meier (KM analysis and Cox proportional hazards model were used for the outcome discontinuation of ≥1 drug regardless of the reason. For the KM estimates a competing risk approach was used to estimate the contribution of each of the reasons over time to the cumulative risk of stopping over time. Results: Data of 1759 patients who started first HAART and had at least one month of clinical follow-up were analyzed. The overall discontinuation risk was 33% over a median follow-up of 12 months. The likelihood of discontinuation by KM was 27% by one year (95% CI 25–29 and 41% by two years (95% CI 38–44. Main reason for stopping at least one drug in regimen was simplification (10%, followed by intolerance (7%, toxicity (5%, failure (2% and other causes (8%. Estimates of the cumulative risk of discontinuation of ≥1 drug over time and according to reason are shown in Figure 1. In a multivariable Cox model independent predictors of discontinuation regardless of the reason were: longer time from HIV diagnosis to date of starting HAART (hazard ratio [HR] 0.96; 95% CI 0.93–1.00; p=0.039, regimens containing ZDV/3TC (HR 2.86; 95% CI 1.42–5.76; p=0.003 vs TDF/FTC and an NNRTI-based regimen (HR 2.47; 95% CI 0.91–6.72; p=0.07 vs regimens not NNRTI-based. Conclusions

  5. Rituximab Treatment Strategy for Patients with Diffuse Large B-Cell Lymphoma after First-Line Therapy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yuan-Rong Ren

    2015-01-01

    Full Text Available Background: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL. But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL. Methods: We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results: Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS and event-free survival (EFS than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94, P = 0.02], progression-free survival (PFS [HR = 0.61, 95% CI (0.52-0.72, P < 0.05], odds ratio (OR [RR = 1.26, 95% CI (1.07-1.47, P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65 P =0.001]. Conclusions: After

  6. Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

    Directory of Open Access Journals (Sweden)

    Giroux Leprieur E

    2016-06-01

    Full Text Available Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy depends on the phenotype of the progression, the

  7. Management of patients with recurrent/advanced cervical cancer beyond first line platinum regimens: Where do we stand? A literature review.

    Science.gov (United States)

    Boussios, Stergios; Seraj, Esmeralda; Zarkavelis, George; Petrakis, Dimitrios; Kollas, Aristomenes; Kafantari, Aikaterini; Assi, Abraam; Tatsi, Konstantina; Pavlidis, Nicholas; Pentheroudakis, George

    2016-12-01

    Cervical cancer is the fourth most common cancer affecting women worldwide. Despite advances in screening and human papillomavirus (HPV) vaccination, a significant number of women present with or develop advanced disease. Palliative platinum-based chemotherapy (CT) is the standard first-line treatment for metastatic/recurrent cervical cancer. The prognosis remains poor and effective second line options are urgently needed. We searched the English-language medical literature as well as relevant guideline databases, published from January 1981 to December 2015 and identified publications related to cervical cancer and its therapies. Our effort was to highlight the available treatment options in the setting of recurrent/metastatic disease. Although there have been important advances in the management of women with cervical cancer, the optimal treatment for patients with locally recurrent and metastatic disease after platinum failure is still problematic. Overall, there is a trend in terms of longer overall survival (OS) and better quality of life for the combination of cisplatin/paclitaxel (PC) as compared to the doublets of cisplatin/topotecan (TC), cisplatin/vinorelbine (VC), and cisplatin/gemcitabine (GC). Currently available single agents beyond first-line platinum-based therapy have limited efficacy in this setting and include topoisomerase inhibitors, vinca alkaloids, taxanes, alkylating agents and antimetabolites. Several targeted therapies have demonstrated activity in advanced cervical cancer. Bevacizumab has been evaluated in a phase III trial using doublets of cisplatin with paclitaxel or topotecan and has been approved in the first-line setting by the U. S. Food and Drug Administration. Selective targeting of angiogenic kinases by tyrosine kinase inhibitors (TKIs) may represent a novel therapeutic tool in this setting, but its use alone or in combination with CT is still investigational. Early reports have implicated PI3KCA somatic mutations suggesting

  8. Initial LDH level can predict the survival benefit from bevacizumab in the first-line setting in Chinese patients with metastatic colorectal cancer

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    Yin CX

    2014-08-01

    Full Text Available Chenxi Yin,1,2,* Chang Jiang,1,2,* Fangxin Liao,1,2 Yuming Rong,1,2 Xiuyu Cai,1,2 Guifang Guo,1,2 Huijuan Qiu,1,2 Xuxian Chen,1,2 Bei Zhang,1,2 Wenzhuo He,1,2 Liangping Xia1,2 1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer, Medicine, 2VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this paper Background: Markers to predict the efficacy of bevacizumab treatment have been not fully validated in most cancers, including metastatic colorectal cancer (mCRC. The aim of this study was to investigate the potential role of lactate dehydrogenase (LDH in predicting the survival benefit from first-line bevacizumab treatment, in Chinese patients with mCRC. Methods: All the patients were diagnosed with mCRC at the Sun Yat-sen University Cancer Center from 2003 to 2013. The study group and the control group were classified by receiving bevacizumab or not. The serum LDH value of all the patients had been detected before the first-line treatment. The primary end point was progression-free survival (PFS. Results: The median PFS of the study and the control group (patients who received bevacizumab or not was 11.3 and 9.1 months, respectively (P=0.004. In the control group, the median PFS of the high LDH level and the low LDH level groups was 6.9 and 10.2 months, respectively (P<0.001. However, in the study group, the corresponding median PFS was 9.9 and 11.9 months, respectively (P=0.145. In addition, for the low LDH level group, the median PFS was 11.9 and 10.2 months for patients who received bevacizumab or not, respectively (P=0.066; however, the median PFS of patients receiving bevacizumab or not was significantly different in the high LDH level group (9.9 and 6.9 months, respectively (P=0.012. Conclusion: The addition of bevacizumab in the first-line treatment setting could improve the

  9. Modality effects in sentence recall.

    Science.gov (United States)

    Goolkasian, Paula; Foos, Paul W; Eaton, Mirrenda

    2009-04-01

    The authors examined the intrusion of lures into sentence recall when manipulating the modality of distractor-word lists and sentences separately. Participants received a list of words followed by a sentence, and the list did or did not contain a lure related to a target in the sentence. Conceptual regeneration of the sentence during recall predicted higher lure intrusions than spontaneous intrusions in all conditions. However, if surface information is remembered, the modality of sentence and list should influence intrusions. The results from Experiment 1 showed that both factors are important, as intrusions were always higher when lures were contained in the distractor-word list and when visual, rather than auditory, sentences were recalled. The authors also found distractor modality to influence the results. In Experiment 2, when interference from the word probe was reduced by removing 40% of the word probes, the disruptive effect of the auditory distractors was attenuated on the trials without the word probe. Also, the authors found lure intrusions to be dependent on the presence of the word probe.

  10. Special issue on Operational Modal Analysis

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Brincker, Rune

    2010-01-01

    Operational Modal Analysis (OMA) is not really a new discipline; it has been present from the very beginning of the development of modal testing and analysis going back to the sixties and early seventies.......Operational Modal Analysis (OMA) is not really a new discipline; it has been present from the very beginning of the development of modal testing and analysis going back to the sixties and early seventies....

  11. Uncertainty calculation in (operational) modal analysis

    Science.gov (United States)

    Pintelon, R.; Guillaume, P.; Schoukens, J.

    2007-08-01

    In (operational) modal analysis the modal parameters of a structure are identified from the response of that structure to (unmeasurable operational) perturbations. A key issue that remains to be solved is the calculation of uncertainty bounds on the estimated modal parameters. The present paper fills this gap. The theory is illustrated by means of a simulation and a real measurement example (operational modal analysis of a bridge).

  12. Extending Modal Transition Systems with Structured Labels

    DEFF Research Database (Denmark)

    Bauer, Sebastian S.; Juhl, Line; Larsen, Kim Guldstrand

    2012-01-01

    We introduce a novel formalism of label-structured modal transition systems that combines the classical may/must modalities on transitions with structured labels that represent quantitative aspects of the model. On the one hand, the specification formalism is general enough to include models like...... study modal and thorough refinement, determinization, parallel composition, conjunction, quotient, and logical characterization of label-structured modal transition systems....

  13. Physical modalities for treating acne and rosacea.

    Science.gov (United States)

    Jalian, H Ray; Levin, Yakir; Wanner, Molly

    2016-06-01

    Physical modalities provide an important adjunct to medical treatment of acne and rosacea. In patients who cannot tolerate or fail medical treatments, physical modalities offer an alternative approach. For cases of acne scarring, phymatous changes of rosacea, and rosacea-associated telangiectasia, physical modalities such as laser and light treatments represent the treatment of choice. We will review the use of laser and light treatments, photodynamic therapy, and other physical modalities such as targeted therapies for the treatment of acne and rosacea.

  14. Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years

    DEFF Research Database (Denmark)

    El Issaoui, Meryam; Giorgione, Veronica; Mamsen, Linn S

    2016-01-01

    the age of 18 years who underwent OTC before (group 1: 31 patients) and after (group 2: 32 patients) their initial cancer treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicular densities (follicles/mm(3)) measured from an ovarian cortical biopsy before OTC. The ovarian volume (mL) of entire...... to have little effect on the follicle pool. This information will improve counseling of young female cancer patients in deciding whether to undergo fertility preservation treatment.......OBJECTIVE: To study the impact of first-line antineoplastic treatment on ovarian reserve in young girls returning for ovarian tissue cryopreservation (OTC) in connection with a relapse. DESIGN: Retrospective case-control study. SETTING: University hospitals. PATIENT(S): Sixty-three girls under...

  15. Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V;

    1996-01-01

    follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical......We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during...... progressive disease, the median positive lead time was 35 days during therapy and 76 days during follow-up. Tumor marker assessment may document that a therapy is effective and ought to be continued in spite of adverse toxic effects, and that a treatment is ineffective and should be stopped to prevent...

  16. Why are ototopical aminoglycosides still first-line therapy for chronic suppurative otitis media? A systematic review and discussion of aminoglycosides versus quinolones.

    Science.gov (United States)

    Harris, A S; Elhassan, H A; Flook, E P

    2016-01-01

    This systematic review aimed to establish that quinolones are as effective as aminoglycosides when used to treat chronic suppurative otitis media. The review included good quality, randomised, controlled trials on human subjects, published in English, that compared topical aminoglycosides with topical quinolones for the treatment of chronic suppurative otitis media. Nine trials met the criteria. Two studies showed a higher clinical cure rate in the quinolone group (93 per cent vs 71 per cent, p = 0.04, and 76 per cent vs 52 per cent, p = 0.009). Four studies showed no statistically significant difference in clinical outcome. A significant difference in microbiological clearance in favour of quinolones was shown in two studies (88 per cent vs 30 per cent, p otitis media and when used as prophylaxis post-myringotomy. Topical quinolones should be considered a first-line treatment for these patients.

  17. Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab

    DEFF Research Database (Denmark)

    Boisen, Mogens K; Dehlendorff, Christian; Linnemann, Dorte

    2014-01-01

    PURPOSE: We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Patients with mCRC treated with first line...... CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain...... with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. CONCLUSIONS: We have identified...

  18. Escherichia coli resistance in uncomplicated urinary tract infection: a model for determining when to change first-line empirical antibiotic choice.

    Science.gov (United States)

    Perfetto, Eleanor M; Gondek, Kathleen

    2002-06-01

    Escherichia coli is typically the causative organism in uncomplicated urinary tract infection (UTI). Resistance rates of E. coli to trimethoprim/sulfamethoxazole (TMP/SMX) are increasing, exceeding 10% in many communities. Guidelines recommend using alternative treatments in these areas. Providers must reevaluate policies to include considerations for E. coli resistance. A model was developed, with cases for illustration, to help organizations determine the resistance rate threshold, where TMP/SMX is no longer first-line therapy. Using published data, a 19% to 21% threshold was derived, supporting a previous report of 22%. The model can aid decision makers updating internal policies to conform with guidelines for the treatment of uncomplicated UTI and to improve care.

  19. Low Incidence of Renal Dysfunction among HIV-Infected Patients on a Tenofovir-Based First Line Antiretroviral Treatment Regimen in Myanmar

    Science.gov (United States)

    Kyaw, Nang Thu Thu; Antierens, Annick; Soe, Kyi Pyar; Woodman, Mike; Das, Mrinalini; Zuu, Moe Khine Lwin; Htwe, Pyae Sone

    2015-01-01

    Background Since 2004, Médecins Sans Frontières-Switzerland has provided treatment and care for people living with HIV in Dawei, Myanmar. Renal function is routinely monitored in patients on tenofovir (TDF)-based antiretroviral treatment (ART), and this provides an opportunity to measure incidence and risk factors for renal dysfunction. Methods We used routinely collected program data on all patients aged ≥15 years starting first-line TDF-based ART between January 2012 and December 2013. Creatinine clearance (CrCl) was assessed at base line and six-monthly, with renal dysfunction defined as CrCl Myanmar, the low incidence of renal toxicity in our patient cohort suggests that routine assessment of CrCl may not be needed and could be targeted to high risk groups if resources permit. PMID:26301416

  20. Intensifying Modifiers for Chinese Modal Verbs.

    Science.gov (United States)

    Huang, Xiaozhao

    While English modal verbs have been studied extensively, Chinese modal verbs have only been analyzed in a general way. A discussion of the six properties of Chinese modal verbs by Li and Thompson (1981, 1997) examined this area, though some of the properties that they proposed appear to be inaccurate or flawed. This paper concentrates on one of…

  1. English Modals - Form, Function and Semantics

    Science.gov (United States)

    Matthews-Bresky, R. J. H.

    1978-01-01

    Gives some general suggestions for teaching English modal auxiliary verbs. For example, "would" and "could" should be taught as verbs in their own right, rather than as forms of "will" and "can." English modals do not exactly match German modals. (IFS/WGA)

  2. On Modality and Its Metaphorical Expressions

    Institute of Scientific and Technical Information of China (English)

    李潜波

    2011-01-01

    This paper is a brief introduction of modality and its metaphorical expressions.lt analyzes types of modality and its different system of orientation followed by the introduction on the metaphorical expressions of modality.The purpose of this study is, th

  3. Rapid drug-susceptibility testing of Mycobacterium tuberculosis clinical isolates to first-line antitubercular drugs by nitrate reductase assay: A comparison with proportion method.

    Science.gov (United States)

    Kohli, Amrish; Bashir, Gulnaz; Fatima, Akeela; Jan, Abiroo; Wani, Nayeem-U-Din; Ahmad, Junaid

    2016-12-01

    Early initiation of therapy in patients with tuberculosis is imperative for its control. Conventional methods of susceptibility testing such as the proportion method (PM) require visual detection and counting of colonies that takes up to 6weeks. Rapid and simple phenotypic methods that have been endorsed by the World Health Organization can serve as alternatives. In this study, we evaluated the colorimetric nitrate reductase assay, which utilizes the detection of nitrate reduction as an indicator of growth much earlier compared with PM (within 7-14days). The susceptibility of 75 clinical isolates of Mycobacterium tuberculosis to four first-line antitubercular drugs was tested by nitrate reductase assay and compared with the standard PM. In this assay, inoculation was done on both drug-free and drug-containing Löwenstein-Jensen medium containing sodium nitrate. After incubation for 7-14days, reduction to nitrite was taken as an indicator of growth, which was detected by color change on addition of Griess reagent. Agreement between nitrate reductase assay and PM was 100% for rifampicin, 97.30% for isoniazid, 93.30% for streptomycin, and 98.60% for ethambutol. Cost/isolate with this assay was found to be approximately two times lesser than that of PM. All results were obtained in 7-14days by nitrate reductase assay, which was significantly rapid compared with 42days taken for obtaining results by PM. Nitrate reductase assay can be used as a rapid and inexpensive method for drug-susceptibility testing of M. tuberculosis for first-line antitubercular drugs without compromising accuracy of standard methods. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

  4. Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Zhi-jie Wang; Ping-ping Li; Hong Sun; Ping Yang; Jie Wang; Tong-tong An; Tony Mok; Lu Yang; Hua Bai; Jun Zhao; Jian-chun Duan; Mei-na Wu; Yu-yan Wang

    2011-01-01

    Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). Methods: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74patients). The primary end point was progression-free survival (PFS). EGFR mutation status was detected using denaturing high-performance liquid chromatography (DHPLC). Results: PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively (hazard ratio [HR],0.99; 95% Confidence Interval [Cl]: 0.69-1.42; P=0.947). In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group (HR, 0.48; 95% Cl:0.27-0.85; P=0.012). In patients with wild type EGFR, the risk for disease progression was comparable between the two groups (HR, 1.23; 95% Cl: 0.61-2.51; P=0.564). No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival (OS) (26.1 months vs. 21.6 months, respectively;HR=0.53; 95% Cl: 0.27 to 1.06; P=0.072). There was also no difference in the incidence of adverse events between the two groups. Conclusions: EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

  5. Recombinant FSH Compared to Clomiphene Citrate as the First-Line in Ovulation Induction in Polycystic Ovary Syndrome Using Newly Designed Pens: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Batool Hossein-Rashidi

    2016-05-01

    Full Text Available Objective: Since there is still controversy regarding the best first-line choice for ovulation induction (OI other than clomiphene citrate (CC in infertile women diagnosed with polycystic ovary syndrome (PCOS, the aim of the present study was to compare recombinant human FSH with CC as the first course of OI in these women.Materials and methods: In this pilot randomized controlled trial, 104 infertile women diagnosed with PCOS were randomized in two groups to receive either CC with the dose of 100mg per day from day 3 of a spontaneous or progestin-induced menstruation for 5 days or rFSH with the starting dose of 50 IU daily {and weekly dose increment of as low as 12.5 IU}, on the day4 of the cycle. They were assessed during a single OI course. The pregnancy rate (PR and live birth rate (LBR were the primary outcomes. The follicular response, endometrial thickness, cancellation of the cycles and ovarian hyper stimulation (OHSS rate were the secondary outcomes.Results: Analyzing data of 96 patients using Chi2 and Fischer’s Exact test (44 in rFSH group and 52 in CC group, both PR and LBR were comparable in the two groups {13.6% vs. 9.6% and 11.4% vs. 9.6% respectively}, with the difference not to be significant (p > 0.05. No cases of OHSS or multiple gestations happened during the treatment course.Conclusion: It seems that rFSH is as efficacious as CC while not with more complications for the first-line OI in infertile women with PCOS. However, due to the limitations of the present study including the small population and the single cycle of treatment, our results did not come out to prove this and more studies with larger study population are needed to compare the cumulative PR and LBR.

  6. The first-line treatment regimens of peripheral T-cell lymphomas%外周T细胞淋巴瘤的一线治疗

    Institute of Scientific and Technical Information of China (English)

    周世勇; 吴少华

    2013-01-01

    Peripheral T-cell lymphomas (PTCLs) are a kind of non-Hodgkin's lymphoma (NHL),which arise from heterogeneous mature T-lymphocyte and include a variety of different subtypes.Compared with B-cell lymphoma,PTCLs are characterized by a lower incidence,resistance to conventional chemotherapy,widespread dissemination,a higher recurrence rate and unfavorable prognosis.At present,the standard first-line treatment regimens have not yet been developed for PTCLs.Though,there are many studies and trials about new drugs and novel intensive regimens,which improve the clinical curative effects and prognosis of PTCL patients significantly.In this paper,the progress of first-line treatment regimens of patients with different PTCL subtypes was reviewed.%外周T细胞淋巴瘤(PTCL)是非霍奇金淋巴瘤的一种类型,起源于异质性的成熟T细胞,包括多种不同亚型.与B细胞淋巴瘤相比,PTCL发病率较低、对传统化疗方案不敏感、病情迁延、易复发、预后较差.目前该病的标准一线治疗尚处于探索阶段,很多新药的研发正在进行,新强化方案的尝试也已展开,从很大程度上提高了PTCL患者的临床疗效及预后.文章着重对目前PTCL不同亚型一线治疗方案的研究进展进行介绍.

  7. Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC.A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS, progression-free survival (PFS, response rate (RR, and different types of toxicity. Hazard ratios (HRs, odds ratios (ORs and their 95% confidence intervals (CIs were pooled using RevMan software.Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC improved survival compared with other platinum-based regimens (PBR in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04, especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02. No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively. Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities.Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

  8. MicroRNA Expression Profiling of Peripheral Blood Samples Predicts Resistance to First-line Sunitinib in Advanced Renal Cell Carcinoma Patients

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    Angelo Gámez-Pozo

    2012-12-01

    Full Text Available Anti-angiogenic therapy benefits many patients with advanced renal cell carcinoma (RCC, but there is still a need for predictive markers that help in selecting the best therapy for individual patients. MicroRNAs (miRNAs regulate cancer cell behavior and may be attractive biomarkers for prognosis and prediction of response. Forty-four patients with RCC were recruited into this observational prospective study conducted in nine Spanish institutions. Peripheral blood samples were taken before initiation of therapy and 14 days later in patients receiving first-line therapy with sunitinib for advanced RCC. miRNA expression in peripheral blood was assessed using microarrays and L2 boosting was applied to filtered miRNA expression data. Several models predicting poor and prolonged response to sunitinib were constructed and evaluated by binary logistic regression. Blood samples from 38 patients and 287 miRNAs were evaluated. Twenty-eight miRNAs of the 287 were related to poor response and 23 of the 287 were related to prolonged response to sunitinib treatment. Predictive models identified populations with differences in the established end points. In the poor response group, median time to progression was 3.5 months and the overall survival was 8.5, whereas in the prolonged response group these values were 24 and 29.5 months, respectively. Ontology analyses pointed out to cancer-related pathways, such angiogenesis and apoptosis. miRNA expression signatures, measured in peripheral blood, may stratify patients with advanced RCC according to their response to first-line therapy with sunitinib, improving diagnostic accuracy. After proper validation, these signatures could be used to tailor therapy in this setting.

  9. First Line Androgen Deprivation Therapy Duration Is Associated with the Efficacy of Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer after Docetaxel

    Science.gov (United States)

    Li, Jian-Ri; Wang, Shian-Shiang; Yang, Cheng-Kuang; Chen, Chuan-Su; Ho, Hao-Chung; Chiu, Kun-Yuan; Hung, Chi-Feng; Cheng, Chen-Li; Yang, Chi-Rei; Chen, Cheng-Che; Wang, Shu-Chi; Lin, Chia-Yen; Ou, Yen-Chuan

    2017-01-01

    Introduction: We performed a chart review study in our castration-resistant prostate cancer (CRPC) patients who received Abiraterone acetate (AA) treatment after docetaxel and identified clinical markers which can predict treatment outcome. Materials and Methods: From 2012 to 2016, 64 patients who received docetaxel after CRPC followed by AA treatment were included. Clinical parameters were recorded and analysis was performed to identify associations between pre-treatment variables and treatment outcome. Results: Thirty three patients (51.6%) achieved a decrease in PSA of 50%. The median PSA progression-free survival and overall survival in the total cohort of 64 patients were 6.6 and 24 months, respectively. Adverse events (AEs) in all grades developed in 35.9% (23/64) patients and mostly were grade 1 or 2. The most common AEs were gastric upset, hypokalemia and elevated liver function tests. Of the eight variables analyzed, first line androgen deprivation therapy (ADT) duration showed positive association to progression free survival (HR 0.98, 95% CI [0.96–0.99], p = 0.012) and overall survival (HR 0.97, 95% CI [0.94–0.99], p = 0.019). Pre-AA PSA and PSA progression ratio showed negative association only to progression free survival (HR 1.0, 95% CI [1.000–1.002], p = 0.025, HR 1.01, 95% CI [1.00–1.01], p < 0.001, respectively). Conclusion: First line ADT duration was positively associated with AA treatment efficacy in progression free survival and overall survival. It can be used as a pre-treatment predictor. PMID:28243202

  10. Bendamustine versus chlorambucil for the first-line treatment of chronic lymphocytic leukemia in England and Wales: a cost-utility analysis.

    Science.gov (United States)

    Woods, Beth; Hawkins, Neil; Dunlop, William; O'Toole, Alison; Bramham-Jones, Steve

    2012-01-01

    To evaluate the cost-effectiveness of bendamustine compared with chlorambucil as first-line treatment for patients with chronic lymphocytic leukemia who would be considered unsuitable for treatment with fludarabine combination chemotherapy regimens. A semi-Markov approach was used to estimate time in each health state. The model was parameterized primarily by using data from a phase III randomized, open-label trial comparing bendamustine with chlorambucil. It captured the increased progression-free survival and improved response rates with bendamustine, and the cost and quality of life impacts of postprogression treatments. The analysis was conducted from the perspective of the National Health Service in England and Wales. A lifetime (35-year) time horizon was used. Deterministic sensitivity analyses, probabilistic sensitivity analyses, and subgroup analyses in older patients and patients with poor performance status were carried out. The estimated incremental cost-effectiveness ratio was £ 11,960 per quality-adjusted life-year. None of the deterministic sensitivity analyses increased the incremental cost-effectiveness ratio by more than £ 2000. Subgroup analyses showed that bendamustine remained cost-effective across different patient groups. Probabilistic sensitivity analysis showed that at the £ 20,000 threshold, bendamustine has a 90% probability of being cost-effective. Bendamustine represents good value for first-line treatment of patients with chronic lymphocytic leukemia who are unsuitable for treatment with fludarabine combination chemotherapy. The incremental cost-effectiveness ratio is below the thresholds commonly applied in England and Wales (£ 20,000-£ 30,000 per quality-adjusted life-year). Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  11. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma.

    Science.gov (United States)

    Herold, Michael; Scholz, Christian W; Rothmann, Frank; Hirt, Carsten; Lakner, Volker; Naumann, Ralph

    2015-09-01

    The randomised, controlled OSHO#39 study showed promising results using first-line mitoxantrone, chlorambucil and prednisolone (MCP) chemotherapy plus rituximab in patients with advanced symptomatic follicular lymphoma (FL) in need of therapy. The aim of this long-term follow-up was to investigate whether clinical benefits are maintained after up to 9 years of observation. Following the 4-year follow-up of OSHO#39, 77 FL patients who received rituximab plus MCP (R-MCP) and 52 patients who received MCP (129 patients alive and not previously censored in total) were followed for 5 additional years in this prospective, non-interventional, observational study. For the efficacy analysis, data were jointly analysed with OSHO#39 data (FL intention-to-treat population: 105 patients R-MCP, 96 MCP). Patients not included in the 5-year follow-up were censored. For surviving patients, median follow-up was 102 months (R-MCP) and 87 months (MCP). Although median overall survival (OS) was not yet reached, OS was longer for patients with R-MCP compared with MCP (p = 0.0057), with 8-year-survival rates of 76.1 versus 55.9%. Further time-to-event data were substantially longer for the R-MCP group than for MCP alone: median progression-free survival (PFS) was 93.4 versus 34.9 months, and median event-free survival (EFS) 89.6 versus 26.5 months. Unplanned subanalyses of patients with and without interferon maintenance showed improved PFS and EFS without an impact on OS. The addition of rituximab to first-line MCP chemotherapy improves clinical outcomes in advanced FL patients and translates into long-term OS benefits. R-MCP remains a promising standard option for this patient group.

  12. Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: A Gynecologic Oncology Group Study.

    Science.gov (United States)

    Burger, Robert A; Brady, Mark F; Bookman, Michael A; Monk, Bradley J; Walker, Joan L; Homesley, Howard D; Fowler, Jeffrey; Greer, Benjamin E; Boente, Matthew; Fleming, Gini F; Lim, Peter C; Rubin, Stephen C; Katsumata, Noriyuki; Liang, Sharon X

    2014-04-20

    To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.

  13. Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

    Science.gov (United States)

    Meini, Genny; Rossetti, Barbara; Bianco, Claudia; Ceccherini-Silberstein, Francesca; Di Giambenedetto, Simona; Sighinolfi, Laura; Monno, Laura; Castagna, Antonella; Rozera, Gabriella; D'Arminio Monforte, Antonella; Zazzi, Maurizio; De Luca, Andrea; Moroni, M.; Angarano, G.; Antinori, A.; Armignacco, O.; d'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; d'Arminio Monforte, A.; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Antinori, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; d'Arminio Monforte, A; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Puoti, M.; Quiros Roldan, E.; Rusconi, S.; Cozzi-Lepri, A.; Cicconi, P.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Giacometti, A.; Costantini, A.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Vanino, E.; Verucchi, G.; Castelli, F.; Quiros Roldan, E.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P.E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Lo Caputo, S.; Cassola, G.; Viscoli, G.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Bonfanti, P.; Caramma, I.; Castelli, A. P.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Puoti, M.; d'Arminio Monforte, A.; Ridolfo, A. L.; Piolini, R.; Castagna, A.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Cicconi, P.; Marchetti, G.; Mussini, C.; Puzzolante, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Cauda, R.; Andreoni, M.; Antinori, A.; Vullo, V.; Cingolani, A.; d'Avino, A.; Ammassari, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Mura, M. S.; Madeddu, G.; Caramello, P.; Di Perri, G.; Orofino, G. C.; Bonora, S.; Sciandra, M.; Pellizzer, G.; Manfrin, V.

    2014-01-01

    Objectives Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment. Methods HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated. Results Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing. Conclusions HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option. PMID:24155059

  14. Prevalence of HIV-1 drug resistance among patients failing first-line ART in Monrovia, Liberia: a cross-sectional study.

    Science.gov (United States)

    Loubet, Paul; Charpentier, Charlotte; Visseaux, Benoit; Borbor, Abraham; Nuta, Cecilia; Adu, Eric; Chapplain, Jean-Marc; Baysah, Maima; Tattevin, Pierre; Yazdanpanah, Yazdan; Descamps, Diane

    2015-01-01

    To assess the prevalence of acquired drug resistance in HIV-1-infected patients living in Monrovia, Liberia, who had clinical and/or immunological failure of first-line ART according to WHO criteria. Patients receiving ART for >1 year with clinical and/or immunological failure were included. Sequencing of protease and reverse transcriptase regions was performed using Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) procedures and sequences were interpreted using the ANRS resistance algorithm. Ninety patients were enrolled. They had been receiving ART for a median time of 42 months and half were receiving zidovudine/lamivudine/nevirapine. Seventy-five per cent of patients were infected with CRF02_AG. Twenty-seven per cent of patients displayed a plasma viral load viruses with PI RAMs. Regarding NRTI drug resistance, 29%, 38%, 63%, 29% and 25% of patients had viruses resistant to zidovudine, stavudine, lamivudine/emtricitabine, abacavir and tenofovir, respectively. Regarding the NNRTI drug class, 56%, 65%, 33% and 42% of patients had viruses resistant to efavirenz, nevirapine, etravirine and rilpivirine, respectively. The high prevalence of acquired drug resistance in patients followed in two centres of the Liberian capital city, documented after a median of 3 years on a first-line ART regimen, jeopardizes the activity of second-line regimens and highlights the need for virological monitoring in these settings. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Cost-effectiveness of adding cetuximab to platinum-based chemotherapy for first-line treatment of recurrent or metastatic head and neck cancer.

    Directory of Open Access Journals (Sweden)

    Malek B Hannouf

    Full Text Available PURPOSE: To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC from the perspective of the Canadian public healthcare system. METHODS: We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%. RESULTS: In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab. CONCLUSION: The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

  16. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Directory of Open Access Journals (Sweden)

    Marie-Anne Vandenhende

    Full Text Available OBJECTIVES: Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS before antiretroviral therapy (ART and at virological failure (VF, in HIV-1 infected patients experiencing VF on first-line ART. METHODS: Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL >500 copies/ml or one VL >1000 copies/ml were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS and UDS at baseline (before ART initiation and VF. RESULTS: Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (p<0.0001 compared to SS. These low-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. CONCLUSION: Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  17. HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 "Aging" study.

    Directory of Open Access Journals (Sweden)

    Sophie Perrin

    Full Text Available BACKGROUND: The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence. METHODS: 49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, NCT01038999. In more than 88% of treated patients, the viral load was 500/mm(3. ROS (reactive oxygen species production and ΔΨm (inner membrane potential were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters. Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively were analysed by western blotting. RESULTS: Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm or morphological (network volume density, fragmentation and branching parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria. CONCLUSIONS: In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1

  18. Genes involved in pericyte-driven tumor maturation predict treatment benefit of first-line FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer.

    Science.gov (United States)

    Volz, N B; Stintzing, S; Zhang, W; Yang, D; Ning, Y; Wakatsuki, T; El-Khoueiry, R E; Li, J E; Kardosh, A; Loupakis, F; Cremolini, C; Falcone, A; Scherer, S J; Lenz, H-J

    2015-02-01

    Pericytes are crucial for angiogenesis. The impact of pericyte function to bevacizumab efficacy in mCRC treatment has not been comprehensively examined. This retrospective study investigated germline polymorphisms in genes related to early pericyte maturation to predict bevacizumab efficacy in 424 patients of two clinical trials treated first line with FOLFIRI+bevacizumab. Eight single-nucleotide polymorphisms (SNPs) were tested for potential biomarker value: RGS5 (regulator of G-protein signaling 5; rs1056515, rs2661280), PDGFR-β (platelet-derived growth factor receptor-β; rs2229562, rs2302273), CSPG4 (chondroitin sulfate proteoglycan NG2; rs8023621, rs1127648) and RALBP1 (RalA binding protein 1; rs10989, rs329007). For progression-free survival (PFS), PDGFR-β (rs2302273) was able to define significantly different patient cohorts in uni- and multivariate testing. RALPB1 (rs329007) showed predictive value for tumor response. The C allele in RGS5 (rs2661280) predicted longer overall survival and CSPG4 rs1127648 was associated with differences in PFS, but for both value was lost when multivariate analysis was applied. A comprehensive statistical analysis revealed that the biomarker value of the SNPs was dependent on primary tumor location. This is the first study to identify pericyte germline polymorphisms associated with clinical outcome in mCRC patients treated first line with FOLFIRI+bevacizumab. The differences seen with regard to primary tumor location may lead to further research to understand the clinical outcome differences seen in right- and left-sided colon cancer.

  19. A pilot study of first-line chemotherapy with 5-FU and Platinum in advanced and recurrent cancer of the cervix

    Directory of Open Access Journals (Sweden)

    Ghaemmaghami F

    2003-06-01

    Full Text Available This study was designed to assess the role of first-line chemotherapy with 5-FU and platinum in the treatment of advanced or recurrent cervical cancer, ten patients with advanced or recurrent cancer of the cervix, with no prior chemotherapy were entered in phase II trial, from Oct. 2000 to Nov. 2001. Eight patients were treated with cis-platinum (50 mg/m2 over 60 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days and two patients with impaired renal function were treated with carboplatin (300 mg/m2 over 15 minutes in first day followed by 5-FU (1 g/m2 over 24 hours for 4 days every three weeks, until progression of disease or prohibitive toxicity had been observed. Median age was 52 years (range: 28-70 years. Ten patients received a total of 42 cycles of chemotherapy. The mean number of chemotherapy cycles was 4.2 (median 4, range: 3-7. Three patients had partial response (30%, CI, 1.7%-58.5%. Mean response duration was 198 days (range: 122-273 days. Four patients required red blood cell transfusions; three of them had grade II and one of them grade III nausea and vomiting Two had fever and neutropenia (one developed acute renal insufficiency, and there wee no treatment related mortalities. First-line chemotherapy with platinum and 5-FU for advanced recurrent cervical cancer is promising and deserves consideration for large phase III trials.

  20. Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years.

    Science.gov (United States)

    El Issaoui, Meryam; Giorgione, Veronica; Mamsen, Linn S; Rechnitzer, Catherine; Birkebæk, Niels; Clausen, Niels; Kelsey, Thomas W; Andersen, Claus Yding

    2016-12-01

    To study the impact of first-line antineoplastic treatment on ovarian reserve in young girls returning for ovarian tissue cryopreservation (OTC) in connection with a relapse. Retrospective case-control study. University hospitals. Sixty-three girls under the age of 18 years who underwent OTC before (group 1: 31 patients) and after (group 2: 32 patients) their initial cancer treatment. None. Follicular densities (follicles/mm(3)) measured from an ovarian cortical biopsy before OTC. The ovarian volume (mL) of entire ovaries excised for OTC was also monitored. There was no statistically significant difference in the mean age or follicular density between groups 1 and 2 (334 ± 476/mm(3) vs. 327 ± 756/mm(3)). In contrast, the ovarian volume and total number of ovarian cortex chips cryopreserved were statistically significantly lower in patients who received gonadotoxic treatment before OTC (mean ± standard deviation [SD]: ovarian volume, 5.3 ± 3.1 mL vs. 2.9 ± 2.1 mL, respectively; number of cortex chips: 21.3 ± 8.1 vs. 15.2 ± 7.1, respectively). The reduction in the estimated ovarian reserve ranged from 10% to 20% in children to around 30% in adolescent girls (>10 years). Girls under the age of 10 tolerate a gonadotoxic insult better than adolescents, who may experience up to a 30% reduction in the ovarian reserve via first-line gonadotoxic treatment, which at present is considered to have little effect on the follicle pool. This information will improve counseling of young female cancer patients in deciding whether to undergo fertility preservation treatment. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  1. First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected Children Treated Through the Universal Coverage Health Program in Thailand.

    Science.gov (United States)

    Teeraananchai, Sirinya; Bunupuradah, Torsak; Puthanakit, Thanyawee; Kerr, Stephen J; Ruxrungtham, Kiat; Chaivooth, Suchada; Bhakeecheep, Sorakij; Law, Matthew G; Chokephaibulkit, Kulkanya

    2017-06-01

    We assessed the treatment outcomes on first-line antiretroviral therapy (ART), and factors associated with switching regimen in HIV-infected children treated through the universal coverage health program (UC) in Thailand. Children aged <15 years at ART initiation who had been receiving ART for at least 6 months between 2008 and 2014 through UC were included in the analysis. The Kaplan-Meier method was used to estimate immunological recovery (IMR), immunological failure, and virological failure (VF). Cox models were used to assess predictors of IMR and VF. Competing risk models were used to assess factors associated with switching to a second-line regimen, with death considered as a competing risk. A total of 4120 children initiated ART at a median (interquartile range) age of 9.3 (5.8-12.0) years. The median duration of ART was 3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five children achieved IMR, and the probability of IMR increased to 76% by 3 years after ART initiation. Among 1054 children switched to second-line regimens, 84% had VF and 19% had immunological failure. The cumulative rate of switching regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged ≥12 years at ART initiation, starting with nonnucleoside reverse-transcriptase inhibitors, and baseline CD4% <10% had an increased risk of switching to second-line regimens. Children receiving ART through UC had good treatment outcomes, although a fifth required switching regimen by 3 years. Earlier treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor first-line regimens in high-risk children may prevent treatment failure.

  2. A phase Ⅱ trial of oxaliplatin plus S-1 as a first-line chemotherapy for patients with advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; SONG Yan; ZHOU Ai-ping; QIN Qiong; CHI Yihebali; HUANG Jing; WANG Jin-wan

    2013-01-01

    Background Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer.We conducted a Phase Ⅱ trial to determine the efficacy and safety of S-1 plus oxaliplatin (SOX regimen) as first-line chemotherapy for patients with unresectable locally advanced or metastatic gastric cancer.Methods Eligible patients had measurable lesions and no previous history of chemotherapy (except adjuvant chemotherapy).Oxaliplatin was administered intravenously at a dose of 130 mg/m2 on day 1.S-1 was administered orally in doses of 80,100,or 120 mg/d according to body surface areas of <1.25 m2,1.25-1.5 m2,or >1.5 m2 respectively;the total dose was divided into two daily doses on days 1-14.Treatments were repeated every 3 weeks until disease progression or intolerable toxicity occurred.Results Forty-three patients were enrolled in the study.All were assessable for efficacy and adverse events.The objective response and disease control rates were 55.8% and 76.7% respectively.The median follow-up time was 16.5 months.The median progression-free survival time was 7 months (95% Cl,5.8-8.2 months) and the median overall survival time was 16.5 months (95% Cl,9.7-23.3 months).The one-year survival rate was 54.2%.Major adverse reactions were grade 3/4 neutropenia (9.3%) and thrombocytopenia (20.9%).Conclusion The SOX regimen with oxaliplatin at a dose of 130 mg/m2 was found to be effective and safe as a first-line chemotherapy in Chinese patients with advanced gastric cancer.

  3. Modality and Task Switching Interactions using Bi-Modal and Bivalent Stimuli

    Science.gov (United States)

    Sandhu, Rajwant; Dyson, Benjamin J.

    2013-01-01

    Investigations of concurrent task and modality switching effects have to date been studied under conditions of uni-modal stimulus presentation. As such, it is difficult to directly compare resultant task and modality switching effects, as the stimuli afford both tasks on each trial, but only one modality. The current study investigated task and…

  4. Noise elimination algorithm for modal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bao, X. X., E-mail: baoxingxian@upc.edu.cn [Department of Naval Architecture and Ocean Engineering, China University of Petroleum (East China), Qingdao 266580 (China); Li, C. L. [Key Laboratory of Marine Geology and Environment, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China); Xiong, C. B. [The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061 (China)

    2015-07-27

    Modal analysis is an ongoing interdisciplinary physical issue. Modal parameters estimation is applied to determine the dynamic characteristics of structures under vibration excitation. Modal analysis is more challenging for the measured vibration response signals are contaminated with noise. This study develops a mathematical algorithm of structured low rank approximation combined with the complex exponential method to estimate the modal parameters. Physical experiments using a steel cantilever beam with ten accelerometers mounted, excited by an impulse load, demonstrate that this method can significantly eliminate noise from measured signals and accurately identify the modal frequencies and damping ratios. This study provides a fundamental mechanism of noise elimination using structured low rank approximation in physical fields.

  5. Politeness of English Modals in Business Negotiations

    Institute of Scientific and Technical Information of China (English)

    YU Zhan-ying

    2016-01-01

    With the development of global economy, more and more business negotiations are proceeding in which conflicts and disputes are inevitable. Business negotiations involve interpersonal relationships, which is usually expressed by mood and mo-dality. Modal verbs, as an essential approach for expressing politeness with rich meanings of modality, are widely employed in business negotiations. This paper focuses on analyzing the polite usages of modal verbs in business negotiations by Politeness Principle. Based on this theory, three interpersonal functions expressed by modal verbs are to be studied:Cost-and-Benefit, Humor and Choice.

  6. ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

    National Research Council Canada - National Science Library

    Bruce E. Johnson; Fairooz Kabbinavar; Louis Fehrenbacher; John Hainsworth; Saifuddin Kasubhai; Bruce Kressel; Chin-Yu Lin; Thomas Marsland; Taral Patel; Jonathan Polikoff; Mark Rubin; Leonard White; James Chih-Hsin Yang; Chris Bowden; Vincent Miller

    2013-01-01

    This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non-small-cell lung cancer (NSCLC...

  7. On modal energy in civil structural control

    Institute of Scientific and Technical Information of China (English)

    Miao PANG; Tie-jiong LOU; Ming ZHAO

    2008-01-01

    A new control strategy based on modal energy criterion is proposed to demonstrate the effectiveness of the control system in reducing structural earthquake responses. The modal control algorithm combining LQR (linear quadratic regulator) control algorithm is adopted in the discrete time-history analysis. The various modal energy forms are derived by definition of the generalized absolute displacement vector. A preliminary numerical study of the effectiveness of this control strategy is carried out on a 20-storey framed steel structural model. The controlled performance of the model is studied from the perspectives of both response and modal energy. Results show that the modal energy-based control strategy is very effective in reducing structural responses as well as in consuming a large amount of modal energy, while augmentation of additional generalized control force corresponding to the modes that contain little modal energy is unnecessary, as it does little help to improve the controlled structural performance.

  8. It does belong together: Cross-modal correspondences influence cross-modal integration during perceptual learning

    OpenAIRE

    Lionel eBrunel; Paulo eCarvalho; Robert L Goldstone

    2015-01-01

    Experiencing a stimulus in one sensory modality is often associated with an experience in another sensory modality. For instance, seeing a lemon might produce a sensation of sourness. This might indicate some kind of cross-modal correspondence between vision and gustation. The aim of the current study was to provide explore whether such cross-modal correspondences influence cross-modal integration during perceptual learning. To that end, we conducted 2 experiments. Using a speeded classificat...

  9. Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study

    Directory of Open Access Journals (Sweden)

    Thaler Josef

    2012-09-01

    Full Text Available Abstract Background Integument-related toxicities are common during epidermal growth factor receptor (EGFR-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial. Methods Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity. Results 154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59; most (98% experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]. Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56% compared with those with grade 0/1 (29%. Mean overall EQ-5D health state index scores (0.81 vs. 0.78, health rating scores (72.5 vs. 71.0 and QLQ-C30 global health status scores (65.8 vs. 66.7 were comparable at baseline vs. safety follow-up (8 weeks after completion, respectively and appeared unaffected by skin toxicity severity. Conclusions First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument

  10. Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Davidson Neville

    2004-07-01

    Full Text Available Abstract Background This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer. Methods Sixty-three patients received irinotecan (250 or 300 mg/m2, 30- to 90-minute intravenous infusion on day 1, immediately followed by folinic acid (20 mg/m2/day and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion days 1 to 5, every four weeks. Results Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3–4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m2. The response rate for the evaluable patient population was 36% (13/36, and 44% (16 patients had stable disease (including 19% of minor response. For the intention-to-treat population, the response rate was 29% (14/49 and 35% (17 patients stable disease (including 14% of minor response. The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3–4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related. Conclusions This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3–4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil

  11. Economic Analysis and Budget Impact of Tenofovir and Entecavir in the First-Line Treatment of Hepatitis B Virus in Italy.

    Science.gov (United States)

    Ruggeri, M; Basile, M; Coretti, S; Drago, C; Cicchetti, A

    2017-08-01

    Chronic hepatitis B is a common, progressive disease, particularly when viral replication is detected. Oral antivirals can suppress viral replication and prevent or delay the development of cirrhosis and liver-related complications. The treatments of chronic hepatitis B cannot totally cure the disease but can prevent its progression to hepatocellular carcinoma, decreasing the levels of both morbidity and mortality. To date, there are several therapies indicated by the international guidelines as first-line treatments for the management of hepatitis B; two of the most effective are those based on either tenofovir or entecavir. The aim of this study is to evaluate the cost-effectiveness of tenofovir and entecavir in the treatment of naïve patients with chronic hepatitis B. The two treatments are compared with the "no treatment" and to one another. The cost-effectiveness analysis was conducted using a Markov model; patients entered one of the following health states: chronic hepatitis, cirrhosis (compensated or decompensated), hepatocellular carcinoma, liver transplantation or death. The analysis was carried out from the perspective of the Italian National Health Service by considering a life-time horizon with cycles lasting 1 year and with costs and QALYs (quality-adjusted life years) discounted at a rate of 3.5%. The results of the model were analysed in terms of incremental cost-effectiveness ratio (ICER). ICERs for tenofovir and entecavir emerging from the comparison versus "no treatment" were equal to €10,274.73 and €16,300.44 per QALY gained, respectively, on the life-time horizon. Tenofovir was dominant in the direct comparison with entecavir, indicating more QALYs and a lower consumption of resources. The Monte Carlo simulation demonstrated that in 97% (tenofovir) and in 85% (entecavir) of the scenarios performed, the cost per QALY fell below the threshold of €30,000/QALY. The budget impact analysis showed savings for tenofovir amounting to 33

  12. First-line antiretroviral treatment failure and associated factors in HIV patients at University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Ayalew MB

    2016-09-01

    Full Text Available Mohammed Biset Ayalew,1 Dawit Kumilachew,2 Assefa Belay,3 Samson Getu,4 Derso Teju,4 Desalegn Endale,4 Yemisirach Tsegaye,4 Zebiba Wale4 1Department of Clinical Pharmacy, 2Department of Pharmaceutics, 3Department of Pharmacology, 4School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Background: Antiretroviral therapy (ART restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital.Patients and methods: A retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients’ sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. P<0.05 was used to declare association.Results: Among the 340 patients enrolled, 205 were females (60.3%. The mean age at ART initiation was 34.4 years. A total of 14 (4.1% patients were found to have treatment failure. The median duration of treatment failure from initiation of treatment was 17.5 months (8–36 months. Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure.Conclusion: The prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm3. Keywords: treatment failure, antiretroviral drugs, risk factor, adherence

  13. Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.

    Science.gov (United States)

    Kitamura, T

    2001-02-01

    Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on

  14. Immunological failure of first-line and switch to second-line antiretroviral therapy among HIV-infected persons in Tanzania: analysis of routinely collected national data

    Science.gov (United States)

    Vanobberghen, Fiona M; Kilama, Bonita; Wringe, Alison; Ramadhani, Angela; Zaba, Basia; Mmbando, Donan; Todd, Jim

    2015-01-01

    Objectives Rates of first-line treatment failure and switches to second-line therapy are key indicators for national HIV programmes. We assessed immunological treatment failure defined by WHO criteria in the Tanzanian national HIV programme. Methods We included adults initiating first-line therapy in 2004–2011 with a pre-treatment CD4 count, and ≥6-months of follow-up. We assessed subhazard ratios (SHR) for immunological treatment failure, and subsequent switch to second-line therapy, using competing risks methods to account for deaths. Results Of 121 308 adults, 7% experienced immunological treatment failure, and 2% died without observed immunological treatment failure, over a median 1.7 years. The 6-year cumulative probability of immunological treatment failure was 19.0% (95% CI 18.5, 19.7) and of death, 5.1% (4.8, 5.4). Immunological treatment failure predictors included earlier year of treatment initiation (P adultos que iniciaban la terapia de primera línea entre el 2004-2011 con un conteo de CD4 antes de recibir el tratamiento, y tras ≥6 meses de seguimiento. Hemos evaluado los subíndices de riesgo del fallo inmunológico en el tratamiento, y el cambio subsecuente a la segunda línea de tratamiento, utilizando análisis de riesgo competitivo para explicar las muertes. Resultados De 121,308 adultos, un 7% experimentó fallo inmunológico, y un 2% murió sin observarse un fallo inmunológico en el tratamiento, a lo largo de una mediana de 1.7 años. La probabilidad acumulada a lo largo de seis años de fallo terapéutico inmunológico era del 19.0% (IC 95% 18.5, 19.7) y de muerte del 5.1% (4.8,5.4). Los vaticinadores de fallo terapéutico inmunológico incluían haber empezado el tratamiento un año antes (pmayor cobertura. PMID:25779383

  15. HIV protease inhibitors do not cause the accumulation of prelamin A in PBMCs from patients receiving first line therapy: the ANRS EP45 "aging" study.

    Directory of Open Access Journals (Sweden)

    Sophie Perrin

    Full Text Available BACKGROUND: The ANRS EP45 "Aging" study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The present report focuses on lamin A processing, a pathway known to be altered in systemic genetic progeroid syndromes. METHODS: 35 HIV-1 infected patients being treated with first line antiretroviral therapy (ART, mean duration at inclusion: 2.7±1.3 years containing boosted protease inhibitors (PI/r (comprising lopinavir/ritonavir in 65% of patients were recruited together with 49 seronegative age- and sex-matched control subjects (http://clinicaltrials.gov/, NCT01038999. In more than 88% of patients, the viral load was 500/mm³. Prelamin A processing in peripheral blood mononuclear cells (PBMCs from patients and controls was analysed by western blotting at inclusion. PBMCs from patients were also investigated at 12 and 24 months after enrolment in the study. PBMCs from healthy controls were also incubated with boosted lopinavir in culture medium containing various concentrations of proteins (4 to 80 g/L. RESULTS: Lamin A precursor was not observed in cohort patient PBMC regardless of the PI/r used, the dose and the plasma concentration. Prelamin A was detected in PBMC incubated in culture medium containing a low protein concentration (4 g/L but not in plasma (60-80 g/L or in medium supplemented with BSA (40 g/L, both of which contain a high protein concentration. CONCLUSIONS: Prelamin A processing abnormalities were not observed in PBMCs from patients under the PI/r first line regimen. Therefore, PI/r do not appear to contribute to lamin A-related aging in PBMCs. In cultured PBMCs from healthy donors, prelamin A processing abnormalities were only observed when the protein concentration in the culture medium was low, thus increasing the amount of PI available to enter cells. ClinicalTrials.gov NCT01038999 http://clinicaltrials.gov/ct2/show/NCT01038999.

  16. The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden

    Directory of Open Access Journals (Sweden)

    Murphy Daniel R

    2012-10-01

    Full Text Available Abstract Background This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO and Glucocorticoid-induced osteoporosis (GIOP. The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. Methods A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated. For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5. Results The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. Conclusions The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO

  17. GEMCYTABIN (CYTOGEM® AND CISPLATIN AS FIRST-LINE THERAPY FOR ADVANCED BLADDER CANCER: RESULTS OF A PROSPECTIVE OPEN-LABELED NON-COMPARATIVE NON-RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2014-08-01

    Full Text Available Purpose.  The primary end-points of the study were overall response rate, progressive-free and overall survival in patients received Gemcytabin (Cytogem® and Cisplatin as first-line therapy for transitional-cell bladder cancer. Secondary end-points were toxicity and safty of the regimen. Material. From February 2005 to March 2007 25 patients with morphologically verified inoperable locally advanced and metastatic transitional-cell bladder cancer were recruited. Men-to-women ratio was 3:1. Median age of the patients was 66,5±6,8 years. All the patients received Cytogem® 1000 mg/m2 days 1, 8, 15, cisplatin 70 mg/m2 on day 2; every 28 days. No more than 6 cycles were allowed if the evidence of disease progression and unacceptable toxicity were not registered. Median follow-up was 36,2±12,1 months.  Results. Complete response was observed in 2 (8%, partial — in 11 (44%, stabilization — in 10 (40%, progression — in 2 (8% of 25 patients. Twelve- and 24-month overall survival was — 51,3% and 22,4% (median 13,4±3,5 (95% CI: 6,6—20,4 months, progressive- free survival — 26% and 13% respectively (median 8,8±1 (95% CI: 6,6—10,6 months. Toxicity was evaluated in 24 patients and occurred in all cases (grade I—II — 16 (67%, grade III—IV — 8 (33%. The main regimen-related toxicity was hematological (neutropenia — 16 (67% (grade I—II — 8 (33%, grade III—IV — 8 (33%, thrombocytopenia — 14 (58% (grade I—II — 10 (41,5%, grade III—IV — 4 (16,5%, anemia — 7 (29% (grade I—II — 5 (21%, grade III—IV — 2 (8%. Hematological toxicity was not associated with com- plications in any case. Non-hematological side-effects were nausea and vomiting in 21 (88% (grade I—II — 67%, grade III — 21%, alopecia — in 11 (44% patients. The regimen-related toxicity was considerable and reversible. No side-effect demanded blood transfusion, antibiotic and/or growth factors administration, and hospital admission.

  18. GEMCYTABIN (CYTOGEM® AND CISPLATIN AS FIRST-LINE THERAPY FOR ADVANCED BLADDER CANCER: RESULTS OF A PROSPECTIVE OPEN-LABELED NON-COMPARATIVE NON-RANDOMIZED STUDY

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2009-01-01

    Full Text Available Purpose.  The primary end-points of the study were overall response rate, progressive-free and overall survival in patients received Gemcytabin (Cytogem® and Cisplatin as first-line therapy for transitional-cell bladder cancer. Secondary end-points were toxicity and safty of the regimen. Material. From February 2005 to March 2007 25 patients with morphologically verified inoperable locally advanced and metastatic transitional-cell bladder cancer were recruited. Men-to-women ratio was 3:1. Median age of the patients was 66,5±6,8 years. All the patients received Cytogem® 1000 mg/m2 days 1, 8, 15, cisplatin 70 mg/m2 on day 2; every 28 days. No more than 6 cycles were allowed if the evidence of disease progression and unacceptable toxicity were not registered. Median follow-up was 36,2±12,1 months.  Results. Complete response was observed in 2 (8%, partial — in 11 (44%, stabilization — in 10 (40%, progression — in 2 (8% of 25 patients. Twelve- and 24-month overall survival was — 51,3% and 22,4% (median 13,4±3,5 (95% CI: 6,6—20,4 months, progressive- free survival — 26% and 13% respectively (median 8,8±1 (95% CI: 6,6—10,6 months. Toxicity was evaluated in 24 patients and occurred in all cases (grade I—II — 16 (67%, grade III—IV — 8 (33%. The main regimen-related toxicity was hematological (neutropenia — 16 (67% (grade I—II — 8 (33%, grade III—IV — 8 (33%, thrombocytopenia — 14 (58% (grade I—II — 10 (41,5%, grade III—IV — 4 (16,5%, anemia — 7 (29% (grade I—II — 5 (21%, grade III—IV — 2 (8%. Hematological toxicity was not associated with com- plications in any case. Non-hematological side-effects were nausea and vomiting in 21 (88% (grade I—II — 67%, grade III — 21%, alopecia — in 11 (44% patients. The regimen-related toxicity was considerable and reversible. No side-effect demanded blood transfusion, antibiotic and/or growth factors administration, and hospital admission.

  19. The efficacy of two-week quadruple first-line therapy with bismuth, lansoprazole, amoxicillin, clarithromycin on Helicobacter pylori eradication: a prospective study.

    Science.gov (United States)

    Ergül, Bilal; Doğan, Zeynal; Sarikaya, Murat; Filik, Levent

    2013-12-01

    To document the efficacy and tolerability of 14-day bismuth-lansoprazole-amoxicillin-clarithromycin (BLAC) regimen for Helicobacter pylori (H. pylori) eradication as a first-line therapy. Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and H. pylori infection was diagnosed through histologic examination of antral and body biopsy samples. Primary end point of this study was to evaluate the eradication rate of 14-day BLAC regimen therapies. H. pylori eradication was assessed using the 13C urea breath test performed 6 weeks after the completion of treatment. All patients were asked to fill in a validated questionnaire to report therapy-related side effects. Each symptom was graded from absent or present. Ninety-seven (21 men and 76 women) were enrolled. All the patients completed the study. The H. pylori eradication rate was 90.7% (88 of 97 patients). Side effects were observed in reasonable percentages, and none of the patients left the study because of drug side effect. Bismuth-lansoprazole-amoxicillin-clarithromycin regimen as a 2-week course achieved an acceptable eradication rate with relatively mild side effects. © 2013 John Wiley & Sons Ltd.

  20. Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer).

    Science.gov (United States)

    Del Mastro, L; Perrone, F; Repetto, L; Manzione, L; Zagonel, V; Fratino, L; Marenco, D; Venturini, M; Maggi, E; Bighin, C; Catzeddu, T; Venturino, A; Rosso, R

    2005-02-01

    First-line chemotherapy regimens suitable for elderly advanced breast cancer patients are still not defined. Women with stage III or IV breast cancer aged > or =70 years were enrolled in a phase II study aimed to evaluate both activity and toxicity of weekly paclitaxel. Among 46 planned patients, at least 18 responses and not more than seven unacceptable toxic events are required for a favourable conclusion. Paclitaxel 80 mg/m(2) was administered weekly for 3 weeks every 28 days. Unacceptable toxicity occurred in seven out of 46 patients evaluated for toxicity [15.2%; exact 95% confidence interval (CI) 7.6% to 28.2%] and was represented by one case of febrile neutropenia, one case of severe allergic reaction and five cases of cardiac toxicity. Among 41 patients evaluated for response, a complete response occurred in two (4.9%) patients and a partial response in 20 (48.8%), with an overall response rate of 53.7% (exact 95% CI 38.7% to 67.9%). The median progression-free survival was 9.7 months (95% CI 8.5-18.7) and median survival was 35.8 months (95% CI 19-not defined). Weekly paclitaxel is highly active in elderly advanced breast cancer patients. Data on cardiovascular complications, however, indicate the need for a careful monitoring of cardiac function before and during chemotherapy.

  1. Long-term use of first-line highly active antiretroviral therapy is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients

    Directory of Open Access Journals (Sweden)

    Haohui Zhu

    2014-09-01

    Full Text Available Objective: To evaluate whether or not highly active antiretroviral therapy is associated with carotid artery stiffness in human immunodeficiency virus-positive patients in Henan Province, China. Method: Fifty human immunodeficiency virus-positive patients with at least a 5-year history of highly active antiretroviral therapy use and 50 human immunodeficiency virus-positive patients without a history of highly active antiretroviral therapy use were enrolled in this study. Carotid artery intima-media thickness and stiffness were determined by quantitative inter-media thickness and quantitative artery stiffness, respectively. Results: No statistically significant difference in carotid artery intima-media thickness and stiffness was observed between groups. A significant association between human immunodeficiency virus infection time and carotid artery stiffness was observed, but no significant association between human immunodeficiency virus infection time and intima-media thickness was found. No significant association between intima-media thickness, stiffness, and CD4+ and CD8+ T-cell counts were observed. Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.

  2. Ampicillin and gentamicin are a useful first-line combination for the management of sepsis in under-five children at an urban hospital in Bangladesh.

    Science.gov (United States)

    Bibi, Samira; Chisti, Mohammod Jobayer; Akram, Farhana; Pietroni, Mark A C

    2012-12-01

    The study evaluated the commonly-used drugs for the management of sepsis and their outcome among under-five children. We evaluated the hospital-records of all paediatric sepsis patients (n = 183) in the intensive care unit (ICU) and longer-stay unit (LSU) of the Dhaka Hospital of icddr,b. These records were collected from the hospital management system (SHEBA) during November 2009 to October 2010. A total of 183 under-five children with clinical sepsis were found during the study period, and 14 (8%) of them were neonates. One hundred and eighty-one patients had received a combination of injection ampicilin and injection gentamicin, and two patients had received the combination of injection ceftriaxone and injection gentamicin. Only 46 (25%) patients required a change of antibiotics to the combination of intravenous ceftriaxone plus gentamicin after non-response of injection ampicilin and injection gentamicin combination; 7/181 (4%) patients died who received injection ampicilin and injection gentamicin whereas none died among the other two patients who received injection ceftriaxone and injection gentamicin (p = 1.00). The combination of injection ampicilin and injection gentamicin as the first-line antibiotics for the management of sepsis in children even beyond the neonatal age is very effective, resulting in lower mortality.

  3. First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study.

    Science.gov (United States)

    Martínez-Calle, Nicolás; Alfonso, Ana; Rifón, José; Herrero, Ignacio; Errasti, Pedro; Rábago, Gregorio; Merino, Juana; Panizo, Ángel; Pardo, Javier; Prósper, Felipe; García-Muñoz, Ricardo; Lecumberri, Ramón; Panizo, Carlos

    2017-01-01

    This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated.

  4. Clomiphene citrate, metformin or a combination of both as the first line ovulation induction drug for Asian Indian women with polycystic ovarian syndrome: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Sujata Kar

    2015-01-01

    Full Text Available Aim: To compare clomiphene citrate (CC, metformin or the combination of CC and metformin as the first line ovulation induction drug in Asian Indian women with polycystic ovary syndrome (PCOS. Methods: One hundred and five newly diagnosed, treatment naive PCOS women were recruited. They were randomized into any of the three groups: Group I (CC 50-150 mg/day, Group II (metformin 1700 mg/day, and Group III (CC + metformin in similar dosage to Groups I and II. Patients underwent follicular monitoring and advice on timed intercourse. The study period was 6 months, or till pregnant, or till CC resistant. Primary outcome studied was live birth rate (LBR. Secondary outcomes were ovulation rate, pregnancy rate, and early pregnancy loss rate. Results: There was no significant difference among the groups in baseline characteristics and biochemical parameters. LBR was 41.6%, 37.5%, and 28.1%, respectively in Groups III, II, and I. Group III (CC + metformin had the highest ovulation (83.3%, pregnancy (50%, and LBRs (41.6%. Group II (metformin was as good as Group I (CC in all the outcomes. CC + metformin (Group III had statistically significantly higher ovulation rate as compared to CC alone (Group I (P = 0.03; odds ratio: 95% confidence interval: 3.888 [1.08-13.997]. Conclusion: Thus, our study shows that metformin was as good as CC in terms of "LBR" and the combination of CC and metformin gave the highest ovulation and LBR.

  5. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

    Science.gov (United States)

    Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

    2014-12-01

    The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); Paplastic anemia.

  6. Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib

    Science.gov (United States)

    Cebrián, Arancha; Gómez del Pulgar, Teresa; Méndez-Vidal, María José; Gonzálvez, María Luisa; Lainez, Nuria; Castellano, Daniel; García-Carbonero, Iciar; Esteban, Emilio; Sáez, Maria Isabel; Villatoro, Rosa; Suárez, Cristina; Carrato, Alfredo; Munárriz-Ferrándiz, Javier; Basterrechea, Laura; García-Alonso, Mirta; González-Larriba, José Luis; Perez-Valderrama, Begoña; Cruz-Jurado, Josefina; González del Alba, Aránzazu; Moreno, Fernando; Reynés, Gaspar; Rodríguez-Remírez, María; Boni, Valentina; Mahillo-Fernández, Ignacio; Martin, Yolanda; Viqueira, Andrea; García-Foncillas, Jesús

    2017-01-01

    Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management. PMID:28117391

  7. The evidence base for efficacy of the low FODMAP diet in irritable bowel syndrome: is it ready for prime time as a first-line therapy?

    Science.gov (United States)

    Gibson, Peter R

    2017-03-01

    Six randomized controlled trials comparing low FODMAP diet with placebo approaches have all indicated efficacy in patients with irritable bowel syndrome (IBS). The studies have provided all the food (n = 3) or utilized dietitian-led education (n = 3). They have variably met criticisms regarding issues such as the choice of placebo, the number of patients studied, the success of blinding, and the duration of the interventions, but the results are uniformly positive for the diet. Real-world experience of the low FODMAP diet has confirmed the findings of the randomized studies, in that about 70% of patients respond. Difficulty in delivering the diet has not been an issue, and the majority of patients find the diet easy to follow when dietitian led. Observational studies have suggested durability of efficacy, even in association with reintroduction of FODMAPs as recommended. Three studies comparing institution of standard dietary guidelines for IBS with the low FODMAP diet have found either similar or improved outcomes with the latter. Low FODMAP diet also has similar efficacy to that of gut-directed hypnotherapy, another strategy with broad benefit in IBS. There are currently no clinically applicable indices that predict response to the diet. In conclusion, clinical trials and observational studies support the notion that a dietitian-led low FODMAP diet is ready for primetime and should be considered as a first-line therapy for patients with IBS where the use of a restrictive diet is appropriate.

  8. Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional Study of Patients and Physicians.

    Directory of Open Access Journals (Sweden)

    Koji Sugano

    Full Text Available Decision-making capacity to provide informed consent regarding treatment is essential among cancer patients. The purpose of this study was to identify the frequency of decision-making incapacity among newly diagnosed older patients with hematological malignancy receiving first-line chemotherapy, to examine factors associated with incapacity and assess physicians' perceptions of patients' decision-making incapacity.Consecutive patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Decision-making capacity was assessed using the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised (SICIATRI-R. Cognitive impairment, depressive condition and other possible associated factors were also evaluated.Among 139 eligible patients registered for this study, 114 completed the survey. Of these, 28 (25%, 95% confidence interval [CI]: 17%-32% were judged as having some extent of decision-making incompetency according to SICIATRI-R. Higher levels of cognitive impairment and increasing age were significantly associated with decision-making incapacity. Physicians experienced difficulty performing competency assessment (Cohen's kappa -0.54.Decision-making incapacity was found to be a common and under-recognized problem in older patients with cancer. Age and assessment of cognitive impairment may provide the opportunity to find patients that are at a high risk of showing decision-making incapacity.

  9. Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

    Science.gov (United States)

    Arenas-Pinto, Alejandro; Thompson, Jennifer; Musoro, Godfrey; Musana, Hellen; Lugemwa, Abbas; Kambugu, Andrew; Mweemba, Aggrey; Atwongyeire, Dickens; Thomason, Margaret J; Walker, A Sarah; Paton, Nicholas I

    2016-02-01

    Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.

  10. Ten-day bismuth-containing quadruple therapy is effective as first-line therapy for Helicobacter pylori-related chronic gastritis: a prospective randomized study in China.

    Science.gov (United States)

    Wang, L; Lin, Z; Chen, S; Li, J; Chen, C; Huang, Z; Ye, B; Ding, J; Li, W; Wu, L; Jiang, Y; Meng, L; Du, Q; Si, J

    2017-06-01

    To investigate the effectiveness of 10-day bismuth-containing quadruple (B-quadruple) treatment as first-line therapy in patients with Helicobacter pylori-related chronic gastritis. A randomized controlled trial was conducted from October 2011 to December 2013 in Zhejiang, China, including patients with H. pylori-related chronic gastritis who were randomly provided either 10-day omeprazole-based triple therapy (OM-triple; omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily) or 10-day B-quadruple therapy (OM-triple + bismuth subcitrate 120 mg four times daily). H. pylori status, pathologic findings and dyspeptic symptoms were assessed at baseline and after 3 months. The primary outcome was H. pylori eradication rates by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary outcomes were the histologic and symptomatic benefits from H. pylori eradication. A total of 351 patients with H. pylori-related chronic gastritis were recruited. The eradication rates of the OM-triple and B-quadruple groups were 58.4% (108/185) and 86.1% (143/166) respectively according to ITT analysis (p pylori eradication were 63.2% (108/171) and 92.3% (143/155) respectively (p pylori-induced chronic gastritis in China. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Combined sildenafil with vacuum erection device therapy in the management of diabetic men with erectile dysfunction after failure of first-line sildenafil monotherapy.

    Science.gov (United States)

    Sun, Lu; Peng, Fang-Li; Yu, Zhi-Ling; Liu, Cai-Ling; Chen, Jun

    2014-12-01

    To evaluate the efficacy and safety of combination therapy of sildenafil plus vacuum erection devices in men with type 2 diabetes mellitus with moderate to severe erectile dysfunction who are dissatisfied with the results of using sildenafil alone. The study included 66 diabetes mellitus patients presenting erectile dysfunction for at least 6 months and dissatisfied with the use of 100 mg sildenafil monotherapy. The patients were randomized in two groups. Those in group A (n = 33) were instructed to use a vacuum erection device only, whereas those in group B (n = 33) were treated with combination therapy, including sildenafil 100 mg and a vacuum erection device. Erectile function was evaluated subjectively using the International Index of Erectile Function, Sexual Encounter Profile questionnaire questions 2 and 3 at visit 1 (baseline; study entry), visit 2 (4 weeks after baseline), and visit 3 (12 weeks after baseline; study end). There were no significant differences in average patient age, duration of diabetes, duration of erectile dysfunction, baseline International Index of Erectile Function scores, hypertension, blood testosterone, smoking and alcohol consumption between two groups. Mean International Index of Erectile Function scores were significantly higher for group B at the 1-month (14.86 ± 2.17 vs 12.41 ± 2.63; P vacuum erection device therapy significantly enhances erectile function, and it is well tolerated by diabetes mellitus patients not responding to first-line sildenafil alone. © 2014 The Japanese Urological Association.

  12. Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma

    Science.gov (United States)

    Zuo, Wenli; Zhu, Xinghu; Yang, Jingke; Mei, Zhenyang; Deng, Mei; Lin, Quande; Song, Yongping; Yin, Qingsong

    2017-01-01

    Abstract Background: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. Case summary: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra. The patient was diagnosed with MM upon examination. A chest computed tomography (CT) scan revealed a round mass in the left lower lobe of the lungs, and a CT-guided needle biopsy uncovered a moderately differentiated adenocarcinoma. There were no additional notable findings in the left lung using positron emission tomography computed tomography (PET-CT). Therefore, a diagnosis of MM with pulmonary adenocarcinoma was made. Surgery was performed to excise the lung cancer. Bortezomib was used as first-line induction therapy against both tumors and lenalidomide was used for maintenance. The patient went into complete remission. Using this combined chemotherapy, the patient has survived for over 3 years since a diagnosis was made despite relapsing twice after the first year. Conclusion: This report clearly delineates the diagnosis and treatment of a rare case of synchronous MM and pulmonary adenocarcinoma, as well as depicts a potentially positive outcome for the patient. It also overviews some diagnostic and therapeutic implications for clinicians. PMID:28072730

  13. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients.

    Science.gov (United States)

    Nattenmüller, Johanna; Wochner, Raoul; Muley, Thomas; Steins, Martin; Hummler, Simone; Teucher, Birgit; Wiskemann, Joachim; Kauczor, Hans-Ulrich; Wielpütz, Mark Oliver; Heussel, Claus Peter

    2017-01-01

    Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (pdecreases in MA, MD and BMI (pDecrease in BMI (HR = 1.303; pincreased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: pdecreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity.

  14. Fully automated (operational) modal analysis

    Science.gov (United States)

    Reynders, Edwin; Houbrechts, Jeroen; De Roeck, Guido

    2012-05-01

    Modal parameter estimation requires a lot of user interaction, especially when parametric system identification methods are used and the modes are selected in a stabilization diagram. In this paper, a fully automated, generally applicable three-stage clustering approach is developed for interpreting such a diagram. It does not require any user-specified parameter or threshold value, and it can be used in an experimental, operational, and combined vibration testing context and with any parametric system identification algorithm. The three stages of the algorithm correspond to the three stages in a manual analysis: setting stabilization thresholds for clearing out the diagram, detecting columns of stable modes, and selecting a representative mode from each column. An extensive validation study illustrates the accuracy and robustness of this automation strategy.

  15. Modal Calculus of Illocutionary Logic

    CERN Document Server

    Schumann, Andrew

    2011-01-01

    The aim of illocutionary logic is to explain how context can affect the meaning of certain special kinds of performative utterances. Recall that performative utterances are understood as follows: a speaker performs the illocutionary act (e.g. act of assertion, of conjecture, of promise) with the illocutionary force (resp. assertion, conjecture, promise) named by an appropriate performative verb in the way of representing himself as performing that act. In the paper I proposed many-valued interpretation of illocutionary forces understood as modal operators. As a result, I built up a non-Archimedean valued logic for formalizing illocutionary acts. A formal many-valued approach to illocutionary logic was offered for the first time.

  16. Learning Multi-modal Similarity

    CERN Document Server

    McFee, Brian

    2010-01-01

    In many applications involving multi-media data, the definition of similarity between items is integral to several key tasks, e.g., nearest-neighbor retrieval, classification, and recommendation. Data in such regimes typically exhibits multiple modalities, such as acoustic and visual content of video. Integrating such heterogeneous data to form a holistic similarity space is therefore a key challenge to be overcome in many real-world applications. We present a novel multiple kernel learning technique for integrating heterogeneous data into a single, unified similarity space. Our algorithm learns an optimal ensemble of kernel transfor- mations which conform to measurements of human perceptual similarity, as expressed by relative comparisons. To cope with the ubiquitous problems of subjectivity and inconsistency in multi- media similarity, we develop graph-based techniques to filter similarity measurements, resulting in a simplified and robust training procedure.

  17. Investigative modalities in infectious keratitis

    Directory of Open Access Journals (Sweden)

    Gupta Noopur

    2008-01-01

    Full Text Available Standard recommended guidelines for diagnosis of infectious keratitis do exist. Based on an extensive Medline literature search, the various investigative modalities available for aiding the diagnosis of microbial keratitis have been reviewed and described briefly. Preferred practice patterns have been outlined and the importance of routine pre-treatment cultures in the primary management of infectious keratitis has been highlighted. Corneal scraping, tear samples and corneal biopsy are few of the specimens needed to carry out the investigative procedures for diagnosis and for initiating therapy in cases of microbial keratitis. In bacterial, fungal and amoebic keratitis, microscopic examination of smears is essential for rapid diagnosis. Potassium hydroxide (KOH wet mount, Gram′s stain and Giemsa stain are widely used and are important for clinicians to start empirical therapy before microbial culture results are available. The usefulness of performing corneal cultures in all cases of suspected infectious keratitis has been well established. In cases of suspected viral keratitis, therapy can be initiated on clinical judgment alone. If a viral culture is needed, scrapings should directly be inoculated into the viral transport media. In vivo confocal microscopy is a useful adjunct to slit lamp bio-microscopy for supplementing diagnosis in most cases and establishing early diagnosis in many cases of non-responding fungal and amoebic keratitis. This is a non-invasive, high resolution technique which allows rapid detection of Acanthamoeba cysts and trophozoites and fungal hyphae in the cornea long before laboratory cultures give conclusive results. Other new modalities for detection of microbial keratitis include molecular diagnostic techniques like polymerase chain reaction, and genetic finger printing by pulsed field gel electrophoresis.

  18. New Ultrasound Modalities in Rheumatology.

    Science.gov (United States)

    Gutierrez, Marwin; Okano, Tadashi; Reginato, Anthony M; Cazenave, Tomas; Ventura-Rios, Lucio; Bertolazzi, Chiara; Pineda, Carlos

    2015-12-01

    Over the years, ultrasound (US) has accumulated important evidence supporting its relevant role for the assessment of inflammatory processes of different rheumatologic diseases, as well as in the follow-up in assessing the response to different therapeutic approaches. This has been possible because of the increase in training, competency, and knowledge, as well as the rapid progress in the US technologies.Currently, some US machines can be equipped by sophisticated software modalities (i.e., 3-dimensional US, elastosonography, automated cardiovascular software, and fusion imaging) that can augment US traditional role as a safe, fast, and easy-to-perform modality and giving it new life and increased relevance in rheumatology. In this article, we evaluated the US developments, from conventional B-mode to more sophisticated technologies, and their potential clinical impact in the field of rheumatology.Three-dimensional US can improve the accuracy of the assessment of bone erosions and the quantification of power Doppler because of its multiplanar view including coronal, axial and sagital view. Elastosonography is still looking for its role in rheumatology. Preliminary works induce us to consider it as a promise tool for the assessment of tendon pathology and skin of patients with connective tissue disorders. The automated method for the measurement of carotid intima-media thickness permits a rapid and accurate assessment. The preliminary published data showed that it is reliable, and valid compared to the traditional method; they also support the future of rheumatologists as the direct operators in evaluating the cardiovascular risk in daily practice. Fusion imaging increases the diagnostic power of US, displaying simultaneously in the monitor, the US image, and the corresponding computed tomography/magnetic resonance imaging image. However, there are no sufficient data supporting its application in daily rheumatologic practice.

  19. Strong Completeness of Coalgebraic Modal Logics

    CERN Document Server

    Schröder, Lutz

    2009-01-01

    Canonical models are of central importance in modal logic, in particular as they witness strong completeness and hence compactness. While the canonical model construction is well understood for Kripke semantics, non-normal modal logics often present subtle difficulties - up to the point that canonical models may fail to exist, as is the case e.g. in most probabilistic logics. Here, we present a generic canonical model construction in the semantic framework of coalgebraic modal logic, which pinpoints coherence conditions between syntax and semantics of modal logics that guarantee strong completeness. We apply this method to reconstruct canonical model theorems that are either known or folklore, and moreover instantiate our method to obtain new strong completeness results. In particular, we prove strong completeness of graded modal logic with finite multiplicities, and of the modal logic of exact probabilities.

  20. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

    Science.gov (United States)

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-01-01

    Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127. PMID:26935876

  1. Experienced Sensory Modalities in Dream Recall

    OpenAIRE

    岡田, 斉

    2000-01-01

    The purpose of the present study is to survey the frequency of visual, auditory, kinaesthetic, cutaneous, organic, gustatory, and olfactory experience in dream recall. A total of 1267 undergraduate students completed a dream recall frequency questionnaire, which contained a question about dream recall frequency and about recall frequency of seven sensory modalities. Results showed that seven sensory modalities were divided into two groups; normally perceived sensory modalities in dreaming, wh...

  2. A survey of modal synthesis methods.

    Science.gov (United States)

    Hart, G. C.; Hurty, W. C.; Collins, J. D.

    1971-01-01

    Several modal synthesis procedures for the dynamic analysis of largy composite structural systems are surveyed. The matrix formulation of the free-free modal synthesis procedures is presented. Also given are schematic flow charts of the analysis procedure used in three prominent methods. The advantages and disadvantages of several modal synthesis methods for different classes of structural problems are presented in order to enable the engineer to select the best procedure for his particular type of problem.

  3. Embolização pré operatória de tumores renais com microparticulas esféricas de tecnologia nacional. (Spherus®-First line Brasil Pre operative embolization of renal tumors with microspherical particles of national technology (Spherus®-First line Brasil

    Directory of Open Access Journals (Sweden)

    Gaudencio Espinosa

    2008-02-01

    Full Text Available Os autores relatam pela primeira vez utilização de uma nova partícula para embolização, constituída de um núcleo de acetato de polivinil revestido por polivinil-álcool, de forma esférica (Spherus®-First Line Brasil, como preparo pré-operatório em três pacientes portadores de neoplasia renal, na intenção de diminuir o tamanho do tumor e prevenir complicações hemorrágicas durante o ato operatório. Estas novas partículas foram projetadas e elaboradas nos laboratórios da COPPE/UFRJ. A embolização intra-arterial pré-operatória com estas novas partículas ocasionou acentuada isquemia em todo o tecido tumoral facilitando o procedimento cirúrgico.The authors report a brand new component for embolization composed by a polivinil acetate core and a polivinil-alcohol coat in a microspherical form ( Spherus®-First Line Brasil used as preoperative management in three patients with renal tumors in an attempt to reduce the size of the tumors and to avoid hemorrhagic complications during the operations. This new component was developed in COPPE/UFRJ laboratories. The preoperative arterial embolization with this new component caused strong ischemia in the tumor tissue , facilitating the operative procedure.

  4. Modalne argumenty teistyczne (Modal Theistic Arguments

    Directory of Open Access Journals (Sweden)

    Graham Oppy

    2011-06-01

    Full Text Available The aim of Oppy’s paper is to provide a general ground for rejecting all kinds of modal theistic arguments. The author claims that all such arguments are questionbegging – before proving the existence of God (defined as a being which exists in every possible world theistic modalist must assume it when choosing his account of logical space (no matter which modal theory it relies on: Lewis’ modal realism, ersatz modal realism, combinatorialism or fictionalism. Two concrete arguments, Plantinga’s ontological argument and Leftow’s cosmological argument, are examples given by Oppy – both have premises which justification must refer to a non-modal question “Does God actually exist?”, concerning the nature of logical space.Oppy rejects suggestion that problems with modal theistic arguments show that there is simply something wrong with our standard modal analyses in terms of possible worlds. According to Oppy, problems with higher-level judgments about the nature of logical space are problems with propositional attitudes, not with modality, andthey need an analysis distinct from the analysis of ground-level modal judgments.

  5. Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug

    Directory of Open Access Journals (Sweden)

    Gonzalez-Block Miguel A

    2005-10-01

    Full Text Available Abstract Introduction Research is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research evidence into drug policy action in Tanzania is often constrained by poor communication between researchers and policy decision-makers, individual perceptions or attitudes towards the drug and hesitation by some policy decision-makers to approve change when they anticipate possible undesirable repercussions should the policy change as proposed. Internationally, literature on the role of researchers on national antimalarial drug policy change is limited. Objectives To describe the (a role of researchers in producing evidence that influenced the Tanzanian government replace chloroquine (CQ with sulfadoxine-pyrimethamine (SP as the first-line drug and the challenges faced in convincing policy-makers, general practitioners, pharmaceutical industry and the general public on the need for change (b challenges ahead before a new drug combination treatment policy is introduced in Tanzania. Methods In-depth interviews were held with national-level policy-makers, malaria control programme managers, pharmaceutical officers, general medical practitioners, medical research library and publications officers, university academicians, heads of medical research institutions and district and regional medical officers. Additional data were obtained through a review of malaria drug policy documents and participant observations were also done. Results In year 2001, the Tanzanian Government officially changed its malaria treatment policy guidelines whereby CQ – the first-line drug for a long time was replaced with SP. This policy decision was supported by research evidence indicating parasite resistance to CQ and clinical CQ treatment failure rates to have reached intolerable levels as compared to SP and amodiaquine (AQ. Research also indicated that since SP was also facing

  6. First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD).

    Science.gov (United States)

    Carrato, Alfredo; Abad, Albert; Massuti, Bartomeu; Grávalos, Cristina; Escudero, Pilar; Longo-Muñoz, Federico; Manzano, José-Luis; Gómez, Auxiliadora; Safont, María José; Gallego, Javier; García-Paredes, Beatriz; Pericay, Carles; Dueñas, Rosario; Rivera, Fernando; Losa, Ferrán; Valladares-Ayerbes, Manuel; González, Encarnación; Aranda, Enrique

    2017-08-01

    In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT-RAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WT-RAS:26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6-1.5]; WT-RAS:13/15; HR: 0.7 [0.4-1.3]). Median OS was 37/41 months (HR:1.0 [0.6-1.8]; WT-RAS: 39/49; HR:0.9 [0.4-1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm. In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and

  7. Indirect treatment comparison of bevacizumab + interferon-α-2a vs tyrosine kinase inhibitors in first-line metastatic renal cell carcinoma therapy

    Directory of Open Access Journals (Sweden)

    Gerald HJ Mickisch

    2011-01-01

    Full Text Available Gerald HJ Mickisch1, Björn Schwander2, Bernard Escudier3, Joaquim Bellmunt4, José P Maroto5, Camillo Porta6, Stefan Walzer7, Uwe Siebert8,91Department of Urology, Center of Operative Urology Bremen, Bremen, Germany; 2Department of Outcomes Research, AiM GmbH Assessment-in-Medicine, Lörrach, Germany; 3Immunotherapy Unit, Institut Gustave Roussy, Villejuif, France; 4Department of Medical Oncology, University Hospital del Mar UPF, Barcelona, Spain; 5Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 6Department of Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy; 7Global Health Economics, F Hoffmann-La Roche Pharmaceuticals AG, Basel, Switzerland; 8Department of Public Health, Medical Decision Making and Health Technology Assessment, UMIT - University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria; 9Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, USABackground: The vascular endothelial growth factor inhibitor bevacizumab (BEV given in combination with interferon-α-2a (IFN, and the tyrosine kinase inhibitors (TKIs sunitinib (SUN and pazopanib (PAZ, have all shown significant increase in progression-free survival (PFS in first-line metastatic renal-cell carcinoma (mRCC therapy. These targeted therapies are currently competing to be primary choice; hence, in the absence of direct head-to-head comparison, there is a need for valid indirect comparison assessment.Methods: Standard indirect comparison methods were applied to independent review PFS data of the pivotal Phase III trials, to determine indirect treatment comparison hazard-ratios (HR with 95% confidence intervals (95% CI. As BEV+IFN and SUN have been compared to IFN, indirect comparison was enabled by the common IFN comparator arms. As PAZ was compared to placebo (PLA, a connector trial (IFN vs PLA was required for the indirect comparison to BEV

  8. Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug.

    Science.gov (United States)

    Mubyazi, Godfrey M; Gonzalez-Block, Miguel A

    2005-10-20

    Research is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research evidence into drug policy action in Tanzania is often constrained by poor communication between researchers and policy decision-makers, individual perceptions or attitudes towards the drug and hesitation by some policy decision-makers to approve change when they anticipate possible undesirable repercussions should the policy change as proposed. Internationally, literature on the role of researchers on national antimalarial drug policy change is limited. To describe the (a) role of researchers in producing evidence that influenced the Tanzanian government replace chloroquine (CQ) with sulfadoxine-pyrimethamine (SP) as the first-line drug and the challenges faced in convincing policy-makers, general practitioners, pharmaceutical industry and the general public on the need for change (b) challenges ahead before a new drug combination treatment policy is introduced in Tanzania. In-depth interviews were held with national-level policy-makers, malaria control programme managers, pharmaceutical officers, general medical practitioners, medical research library and publications officers, university academicians, heads of medical research institutions and district and regional medical officers. Additional data were obtained through a review of malaria drug policy documents and participant observations were also done. In year 2001, the Tanzanian Government officially changed its malaria treatment policy guidelines whereby CQ--the first-line drug for a long time was replaced with SP. This policy decision was supported by research evidence indicating parasite resistance to CQ and clinical CQ treatment failure rates to have reached intolerable levels as compared to SP and amodiaquine (AQ). Research also indicated that since SP was also facing rising resistance trend, the need for a more effective drug was

  9. Bendamustine plus rituximab versus R-CHOP as first-line treatment for patients with indolent non-Hodgkin's lymphoma: evidence from a multicenter, retrospective study.

    Science.gov (United States)

    Mondello, Patrizia; Steiner, Normann; Willenbacher, Wolfgang; Wasle, Ines; Zaja, Francesco; Zambello, Renato; Visentin, Andrea; Mauro, Endri; Ferrero, Simone; Ghione, Paola; Pitini, Vincenzo; Cuzzocrea, Salvatore; Mian, Michael

    2016-06-01

    The optimal first-line treatment for advanced low-grade non-Hodgkin lymphomas (LG-NHL) is still highly debated. Recently, the StiL and the BRIGHT trials showed that the combination of rituximab and bendamustine (R-B) is non-inferior to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with a better toxicity profile. Utilizing a retrospective analysis, we compared the efficacy and safety of both regimens in clinical practice. From November 1995 to January 2014, 263 LG-NHL patients treated with either R-B or R-CHOP were retrospectively assessed in seven European cancer centers. Ninety patients were treated with R-B and 173 with R-CHOP. Overall response rate was 94 and 92 % for the R-B and the R-CHOP group, respectively. The percentage of complete response was similar for both groups (63 vs. 66 % with R-B and R-CHOP, respectively; p = 0.8). R-B was better tolerated and less toxic than R-CHOP. The median follow-up was 6.8 and 5.9 years for the R-CHOP and the R-B group, respectively. Overall, no difference in progression-free survival (PFS) (108 vs. 110 months; p = 0.1) was observed in the R-B group compared to the R-CHOP cohort. Nevertheless, R-B significantly prolonged PFS in FL patients (152 and 132 months in the R-B and R-CHOP group, respectively; p = 0.05). However, this result was not verified in multivariate analysis probably due to the limits of the present study. We confirm that the R-B regimen administered in patients with LG-NHL is an effective and less toxic therapeutic option than R-CHOP in clinical practice.

  10. Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model.

    Science.gov (United States)

    Brunelli, Steven M; Sibbel, Scott P; Van Wyck, David; Sharma, Amit; Hsieh, Andrew; Chertow, Glenn M

    2017-03-01

    Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

  11. Adherence to drug-refill is a useful early warning indicator of virologic and immunologic failure among HIV patients on first-line ART in South Africa.

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    Ziad El-Khatib

    Full Text Available BACKGROUND: Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI recipients in South Africa. METHODS: In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml and immunologic failure (as defined by WHO. RESULTS: After a median of 15 months on ART, 19% (n = 88 and 19% (n = 87 had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01. In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7, and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9, adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02. CONCLUSION: One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure.

  12. Vonoprazan-Based Regimen Is More Useful than PPI-Based One as a First-Line Helicobacter pylori Eradication: A Randomized Controlled Trial

    Science.gov (United States)

    Tanaka, Naoki; Kubota, Daisuke; Miyajima, Masayuki; Tokutake, Koujiro; Imai, Ryujiro; Fujisawa, Toru; Mori, Hiromitsu; Matsuda, Yoshiaki; Wada, Shuichi; Horiuchi, Akira; Kiyosawa, Kendo

    2017-01-01

    Background. A new agent, potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer advantages over conventional H. pylori eradication therapies. We aimed to compare the eradication rate between VPZ-based treatment and PPI-based one. Methods. This randomized controlled trial was designed to assign 141 patients with H. pylori-positive gastritis to VPZ group (VPZ 20 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days) or PPI group (rabeprazole 20 mg or lansoprazole 30 mg, amoxicillin 750 mg, and clarithromycin 200 or 400 mg twice daily for 7 days). Primary endpoints were eradication rates and adverse events. Results. Seventy of 72 patients in VPZ group and 63 of 69 patients in PPI group completed the treatment after 7 days. The eradication rate was significantly higher in VPZ group than PPI group by intention-to-treat analysis (95.8% versus 69.6%, P = 0.00003, 95% confidence interval [CI] 88.3-99.1% versus 57.3-80.1%) and per-protocol analysis (95.7% versus 71.4%, P = 0.0002, 95% CI 88.0-99.1% versus 58.7-82.1%). The incidence of adverse events was not different between the groups (26.3% in VPZ group versus 37.7% in PPI group, P = 0.15). Conclusion. VPZ-based regimen is more useful than that PPI-based regimen as a first-line H. pylori eradication therapy.

  13. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study.

    Science.gov (United States)

    Hillmen, Peter; Gribben, John G; Follows, George A; Milligan, Donald; Sayala, Hazem A; Moreton, Paul; Oscier, David G; Dearden, Claire E; Kennedy, Daniel B; Pettitt, Andrew R; Nathwani, Amit; Varghese, Abraham; Cohen, Dena; Rawstron, Andy; Oertel, Stephan; Pocock, Christopher F E

    2014-04-20

    Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL. Patients with first-line CLL were treated with rituximab (375 mg/m(2) on day 1, cycle one, and 500 mg/m(2) thereafter) plus chlorambucil (10 mg/m(2)/d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety. A total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (range, 43 to 86 years), with patients having a median of seven comorbidities. Hematologic toxicities accounted for most grade 3/4 adverse events reported, with neutropenia and lymphopenia both occurring in 41% of patients and leukopenia in 23%. Overall response rates were 84%, with CR achieved in 10% of patients. Median progression-free survival was 23.5 months; median overall survival was not reached. These results compare favorably with previously published results for chlorambucil monotherapy, suggesting that the addition of rituximab to chlorambucil may improve efficacy with no unexpected adverse events. R-chlorambucil may improve outcome for patients who are ineligible for fludarabine-based treatments.

  14. Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

    Directory of Open Access Journals (Sweden)

    Soraya S Andrade

    2006-11-01

    Full Text Available Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%, followed by Klebsiella spp. (7%, Proteus mirabilis (6.4%, Enterococcus spp. (5.6%, and Pseudomonas aeruginosa (4.6%. Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%, TMP/SMX (40.4%, ciprofloxacin (21.6%, and gatifloxacin (17.1%. Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively, and P. mirabilis (71.8 and 84.6%, respectively. For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

  15. Tissue microRNAs as predictors of outcome in patients with metastatic colorectal cancer treated with first line Capecitabine and Oxaliplatin with or without Bevacizumab.

    Science.gov (United States)

    Boisen, Mogens K; Dehlendorff, Christian; Linnemann, Dorte; Nielsen, Boye S; Larsen, Jim S; Osterlind, Kell; Nielsen, Svend E; Tarpgaard, Line S; Qvortrup, Camilla; Pfeiffer, Per; Holländer, Niels H; Keldsen, Nina; Hansen, Torben F; Jensen, Brita B; Høgdall, Estrid V S; Jensen, Benny V; Johansen, Julia S

    2014-01-01

    We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs. In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials.

  16. Tissue microRNAs as predictors of outcome in patients with metastatic colorectal cancer treated with first line Capecitabine and Oxaliplatin with or without Bevacizumab.

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    Mogens K Boisen

    Full Text Available PURPOSE: We tested the hypothesis that expression of microRNAs (miRNAs in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX in patients with metastatic colorectal cancer (mCRC. EXPERIMENTAL DESIGN: Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV: screening (n = 212 and validation (n = 121 cohorts, or CAPEOX alone: control cohort (n = 127, were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR arrays and expression levels were related to time to disease progression (TTP and overall survival (OS. Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH was done for selected miRNAs. RESULTS: In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. CONCLUSIONS: We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials.

  17. Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

    Science.gov (United States)

    Díaz-Rubio, Eduardo; Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Reboredo, Margarita; Manzano, José Luis; Rivera, Fernando; Safont, M José; Montagut, Clara; González, Encarnación; Benavides, Manuel; Marcuello, Eugenio; Cervantes, Andrés; Martínez de Prado, Purificación; Fernández-Martos, Carlos; Arrivi, Antonio; Bando, Inmaculada; Aranda, Enrique

    2012-01-01

    In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64). This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

  18. Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

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    Eduardo Díaz-Rubio

    Full Text Available BACKGROUND: In the MACRO study, patients with metastatic colorectal cancer (mCRC were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS, overall survival (OS and response rates. METHODOLOGY/PRINCIPAL FINDINGS: KRAS data (tumour KRAS status and type of mutation were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1% in the MACRO study. Wild-type (WT KRAS tumours were found in 219 patients (56% and mutant (MT KRAS in 175 patients (44%. Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77. The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96. Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5% with WT KRAS tumours and 76 patients (43.4% with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64. CONCLUSIONS/SIGNIFICANCE: This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

  19. A phase II study of weekly docetaxel-cisplatin as first-line treatment for advanced non-small cell lung cancer.

    Science.gov (United States)

    Binder, Daniel; Hackenthal, Matthias; Graseck, Lutz; Schweisfurth, Hans; Schäper, Christoph; Krüll, Matthias; Temmesfeld-Wollbrück, Bettina; Suttorp, Norbert; Beinert, Thomas; Hellriegel, Klaus-Peter

    2009-09-01

    The combination of docetaxel and cisplatin is an effective first-line regimen in patients with advanced non-small cell lung cancer. However, the recommended three-weekly schedule is associated with frequent neutropenia and infections. Because of the toxicity of cisplatin, patients may need to be hospitalized to ensure adequate hydration. The aim of this study was to assess the efficacy and tolerability of a weekly schedule of docetaxel and cisplatin. Patients with inoperable stage International Union Against Cancer IIIB (malignant effusion) or IV non-small cell lung cancer received docetaxel (35 mg/m(2), 30 minutes infusion) and cisplatin (25 mg/m(2), 30 minutes infusion) on days 1, 8, and 15, every 4 weeks for 4 to 6 cycles. Ondansetron (8 mg) and dexamethasone (8 mg) were given intravenously before chemotherapy. The patients received oral dexamethasone 2 x 4 mg daily from the day before until the day after chemotherapy. NK1-antagonists were given at the investigator's discretion. The majority of patients was treated in outpatient departments. Safety was assessed using CTCAE v3.0. The primary end point was response rate (RECIST). Forty-four patients were included. Twelve of 44 patients achieved an objective response (11 partial, 1 complete, intent-to-treat response rate 27%). Median time to progression was 4.4 months (95% confidence interval: 4.0-4.7) and median survival 9.6 months (95% confidence interval: 2.9-16.2). Patients received a median of three full cycles. Four patients (9%) required dose reductions. No cases of febrile neutropenia or grade 2 to 4 thrombocytopenia were observed. One patient (2%) experienced grade 3/4 nausea and vomiting. Weekly docetaxel-cisplatin demonstrated comparable efficacy with three-weekly schedules. Although the frequencies of neutropenia and febrile neutropenia were low, non-neutropenic infections remained a problem. Because of relatively short hydration, the schedule can be safely administered in an outpatient setting.

  20. Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer in Korea.

    Science.gov (United States)

    Beom, Seung Hoon; Oh, Jisu; Kim, Tae-Yong; Lee, Kyung-Hun; Yang, Yaewon; Suh, Koung Jin; Moon, Hyeong-Gon; Han, Sae-Won; Oh, Do-Youn; Han, Wonshik; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

    2017-04-01

    Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

  1. Comparison of gemcitabin, cisplatin, and dexamethasone (GDP), CHOP, and CHOPE in the first-line treatment of peripheral T-cell lymphomas.

    Science.gov (United States)

    Jia, Bo; Hu, Shaoxuan; Yang, Jianliang; Zhou, Shengyu; Liu, Peng; Qin, Yan; Gui, Lin; Yang, Sheng; Lin, Hua; Zhang, Changgong; Xing, Puyuan; Wang, Lin; Dong, Mei; Zhou, Liqiang; Sun, Yan; He, Xiaohui; Shi, Yuankai

    2016-10-01

    Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients. Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen. Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174). CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

  2. Determinants of immunological failure among clients on the first line treatment with highly active antiretroviral drugs in Dar es Salaam, Tanzania

    Institute of Scientific and Technical Information of China (English)

    Anthony Kapesa; Daniel Magesa; Alexander William; John Kaswija; Jeremiah Seni; Cyprian Makwaya

    2014-01-01

    Objective:To determine socio-cultural, demographic and highly active antiretroviral therapy (HAART) program-related factors associated with immunological failure (IF) among clients on HAART in Dar es Salaam care and treatment clinics. Methods:A 1:2 matched case control study was done from February to April 2012 in HIV/AIDS care and treatment clinics in Dar es Salaam. Data were collected from National AIDS Control Program (NACP) data base and patient’s charts to obtain 60 sets of study participants who were interviewed using the structured questionnaire. Data analysis was done by using EPI Info 3.5.1 version. Results:The mean age of all study participants was (42.00±9.07) years with 35% (63) being males. History of poor antiretroviral therapy (ART) adherence due to exposure to drug holiday with loss to follow up (OR=11.96;95%CI=2.07-69.26), history of changing care and treatment clinics (OR=12.07;95%CI=2.10-69.27) and the lack of treatment supporter (OR=23.26;95%CI=1.85-291.66) were found to be strongly associated with the occurrence of first line HAART-IF. Conclusions:HAART-IF in Dar es Salaam is associated with ART programmatic and patients’ centered challenges. There is a need to review the approaches on ensuring ART adherence, clients follow up and referral system so as to reduce the incidence of IF as we move to a more decentralized peripheral drug picks clinical initiative.

  3. Modality-specific and modality-independent components of the human imagery system

    NARCIS (Netherlands)

    Daselaar, S.M.; Porat, Y.; Huijbers, W.; Pennartz, C.M.A.

    2010-01-01

    magery research typically deals with the commonalities and differences between imagery and perception. As such, it is usually confined to one specific modality. Yet, it is likely that some of the underlying processes are shared between different sensory modalities while others are modality-specific.

  4. Modality-specific and modality-independent components of the human imagery system

    NARCIS (Netherlands)

    S.M. Daselaar; Y. Porat; W. Huijbers; C.M.A. Pennartz

    2010-01-01

    Imagery research typically deals with the commonalities and differences between imagery and perception. As such, it is usually confined to one specific modality. Yet, it is likely that some of the underlying processes are shared between different sensory modalities while others are modality-specific

  5. Functions of modal particles in Hungarian

    OpenAIRE

    Marusynets, Marianna

    2014-01-01

    The article discusses the functions of Hungarian modal particles from the Relevance Theory perspective, which offers a cognitive account of utterance interpretation. It is argued that Hungarian modal particles govern the selection of context by guiding the hearer towards relevant interpretation.

  6. Swedish Modal Particles in a Contrastive Perspective.

    Science.gov (United States)

    Aijmer, Karen

    1996-01-01

    Presents a study based on the analysis of contrastive Swedish-English data on modal particles. The article maintains that the meaning of modal particles requires an analysis of their pragmatic aspects such as the relation between the interlocutors. The analysis most accurately accounting for the multifunctionality of the particles is based on a…

  7. Pragmatics in Interlanguage: German Modal Particles.

    Science.gov (United States)

    Mollering, Martina; Nunan, David

    1995-01-01

    Argues that mastery of modal particles is important for interpersonal aspects of language development. The article outlines the difficulty of learning and teaching German modal particles with regard to the theoretical explication. The study shows how a teaching program improved initially poor comprehension and production skills in the area of…

  8. Three-valued logics in modal logic

    NARCIS (Netherlands)

    Kooi, Barteld; Tamminga, Allard

    2013-01-01

    Every truth-functional three-valued propositional logic can be conservatively translated into the modal logic S5. We prove this claim constructively in two steps. First, we define a Translation Manual that converts any propositional formula of any three-valued logic into a modal formula. Second, we

  9. Methodological Constraints for Detecting the Modality Effect

    Science.gov (United States)

    Schoor, Cornelia; Bannert, Maria; Jahn, Verena

    2011-01-01

    Introduction: The aim of our research was to investigate the modality effect in more detail by measuring it in a direct way. Two studies were conducted using the same subject and material. Method: Computer-based learning material was presented on several screens, each containing a short text and a picture. Modality was varied by presenting written…

  10. Pragmatics in Interlanguage: German Modal Particles.

    Science.gov (United States)

    Mollering, Martina; Nunan, David

    1995-01-01

    Argues that mastery of modal particles is important for interpersonal aspects of language development. The article outlines the difficulty of learning and teaching German modal particles with regard to the theoretical explication. The study shows how a teaching program improved initially poor comprehension and production skills in the area of…

  11. History of Civil Engineering Modal Analysis

    DEFF Research Database (Denmark)

    Brincker, Rune

    2008-01-01

    techniques are available for civil engineering modal analysis. The testing of civil structures defers from the traditional modal testing in the sense, that very often it is difficult, or sometimes impossible, to artificially excite a large civil engineering structure. Also, many times, even though...

  12. Large proximal ureteral stones: Ideal treatment modality?

    Directory of Open Access Journals (Sweden)

    B Kadyan

    2016-01-01

    Conclusion: Laparoscopic transperitoneal ureterolithotomy is a minimally invasive, safe and effective treatment modality and should be recommended to all patients of impacted large proximal stones, which are not amenable to URS or extracorporeal shock-wave lithotripsy or as a primary modality of choice especially if patient is otherwise candidate for open surgery.

  13. History of Civil Engineering Modal Analysis

    DEFF Research Database (Denmark)

    Brincker, Rune

    2008-01-01

    techniques are available for civil engineering modal analysis. The testing of civil structures defers from the traditional modal testing in the sense, that very often it is difficult, or sometimes impossible, to artificially excite a large civil engineering structure. Also, many times, even though...

  14. Modal Transition Systems with Weight Intervals

    DEFF Research Database (Denmark)

    Juhl, Line; Larsen, Kim Guldstrand; Srba, Jiri

    2012-01-01

    We propose weighted modal transition systems, an extension to the well-studied specification formalism of modal transition systems that allows to express both required and optional behaviours of their intended implementations. In our extension we decorate each transition with a weight interval th...

  15. Reasoning About Space : The Modal Way

    NARCIS (Netherlands)

    Aiello, Marco; Benthem, Johan van; Bezhanishvili, Guram

    2003-01-01

    We investigate the topological interpretation of modal logic in modern terms, using a new notion of bisimulation. We look at modal logics with interesting topological content, presenting, among others, a new proof of McKinsey and Tarski's theorem on completeness of S4 with respect to the real line,

  16. Language: perspectives from another modality.

    Science.gov (United States)

    Bellugi, U; Klima, E S

    1979-01-01

    Human languages have been forged in auditory-vocal channels throughout evolution. This paper examines the formal properties of a communication system that has developed in the absence of speech: the sign language of the deaf. The objective is to investigate to what extent the overall form and organization of language is determined by the articulatory and perceptual modality in which it has developed (its transmission system) and to what extent its form and organization represent more fundamental aspects of the human mind (intellect). Experimental and linguistic evidence is brought to bear on the analysis of the sign: studies of coding and processing of signs in memory; of slips of the hand; of historical change in signs over time; the heightened use of language in poetry and wit. American Sign Language differs dramatically from English and other spoken languages in the mechanisms by which its lexical units are modified. For the form of its morphological processes, the mode in which the language develops appears to make a crucial difference. Finally, the issue of cerebral specialization with respect to a visual-manual language is addressed.

  17. Modal interference in spiky nanoshells.

    Science.gov (United States)

    Hastings, Simon P; Qian, Zhaoxia; Swanglap, Pattanawit; Fang, Ying; Engheta, Nader; Park, So-Jung; Link, Stephan; Fakhraai, Zahra

    2015-05-04

    Near-field enhancement of the electric field by metallic nanostructures is important in non-linear optical applications such as surface enhanced Raman scattering. One approach to producing strong localization of the electric field is to couple a dark, non-radiating plasmonic mode with a broad dipolar resonator that is detectable in the far-field. However, characterizing or predicting the degree of the coupling between these modes for a complicated nanostructure can be quite challenging. Here we develop a robust method to solve the T-matrix, the matrix that predicts the scattered electric fields of the incident light, based on finite-difference time-domain (FDTD) simulations and least square fitting algorithms. This method allows us to simultaneously calculate the T-matrix for a broad spectral range. Using this method, the coupling between the electric dipole and quadrupole modes of spiky nanoshells is evaluated. It is shown that the built-in disorder in the structure of these nanoshells allows for coupling between the dipole modes of various orientations as well as coupling between the dipole and the quadrupole modes. A coupling strength of about 5% between these modes can explain the apparent interference features observed in the single particle scattering spectrum. This effect is experimentally verified by single particle backscattering measurements of spiky nanoshells. The modal interference in disordered spiky nanoshells can explain the origin of the spectrally broad quadrupole resonances that result in strong Quadrupole Enhanced Raman Scattering (QERS) in these nanoparticles.

  18. Modal analysis of PATHFINDER unmanned air vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Woehrle, T.G.; Costerus, B.W.; Lee, C.L.

    1994-10-19

    An experimental modal analysis was performed on PATHFINDER, a 450-lb, 100-ft wing span, flying-wing-design aircraft powered by solar/electric motors. The aircraft was softly suspended and then excited using random input from a long-stroke shaker. Modal data was taken from 92 measurement locations on the aircraft using newly designed, lightweight, tri-axial accelerometers. A conventional PC-based data acquisition system provided data handling. Modal parameters were calculated, and animated mode shapes were produced using SMS STARStruct{trademark} Modal Analysis System software. The modal parameters will be used for validation of finite element models, optimum placement of onboard accelerometers during flight testing, and vibration isolation design of sensor platforms.

  19. Boilerplate Test Article (BTA) Modal Test Correlation

    Science.gov (United States)

    Vassilakos, Gregory J.; Corliss, James M.; Mark, Stephen D.

    2017-01-01

    Modal testing of the Boilerplate Test Article (BTA) was performed to obtain data to determine the accuracy of the BTA LS- DYNA model in determining the structural response. The BTA is a full-scale steel and aluminum test article that is representative of the Orion Crew Module (CM), with similar outer-mold-line geometry, mass properties, and some similar structural features, including an internal pressure vessel connected to a backshell and heatshield via longerons, Retention and Release (R&R) brackets, and an aft ring. The structural design of the Orion CM is being developed based on LS-DYNA water landing simulations. To obtain data to evaluate the accuracy of LS-DYNA water impact landing simulations, a series of BTA water impacts was conducted at NASA Langley Research Center (LaRC). Discrepancies between test and simulation data are attributed to three causes:(1) Test data variability and uncertainty, (2) LS-DYNA water model and fluid-structure coupling approximations; and (3) LS-DYNA structural modeling approximations. Two activities have been undertaken to assess the accuracy of the BTA LS-DYNA structural model separately from the fluid-structure coupling portion of the water landing simulations: 1) modal testing, and 2) static load testing. The results from the static load tests are documented in a separate report. For the modal test series, the following tests were performed: (1) BTA Fully-Assembled Model Test, (2) BTA Backshell Removed Modal Test, (3) Standalone Heatshield Modal Test, (4) Standalone Windward Backshell Panel Modal Test; and (5) Standalone Leeward Backshell Panel Modal Test. This report documents findings from correlation of modal test data with LS-DYNA modal analysis results. The following figures illustrate the correlation of the modal frequencies. Where multiple closely spaced modes have been identified, the points representing the upper and lower frequencies are shown connected by a dotted line.

  20. Value of {sup 18}F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

    Energy Technology Data Exchange (ETDEWEB)

    Palard-Novello, X. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Querellou, S.; Abgral, R.; Salauen, P.Y. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Brest University, EA3878, GETBO, IFR148, Brest (France); Gouillou, M. [Institut National de la Sante et de la Recherche Medicale (INSERM), Clinical Investigation Centre (CIC) 1412, Brest (France); Saraux, A.; Devauchelle-Pensec, V. [Brest University Hospital, Department of Rheumatology, Brest (France); Brest University, EA 2216, ESPRI 29, Brest (France); Marhadour, T. [Brest University Hospital, Department of Rheumatology, Brest (France); Garrigues, F. [Brest University Hospital, Department of Radiology, Brest (France)

    2016-04-15

    To evaluate the use of {sup 18}F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∇SUVmax and the other parameters including ∇PMR-AS, ∇CRP and ∇ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity. (orig.)

  1. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  2. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients

    Science.gov (United States)

    Nattenmüller, Johanna; Wochner, Raoul; Muley, Thomas; Steins, Martin; Hummler, Simone; Teucher, Birgit; Wiskemann, Joachim; Kauczor, Hans-Ulrich; Wielpütz, Mark Oliver; Heussel, Claus Peter

    2017-01-01

    Introduction Cachexia and sarcopenia are associated with poor outcome and increased chemotherapy-induced toxicity in lung cancer patients. However, the complex interplay of obesity, sarcopenia and cachexia, and its impact on survival in the context of first-line-chemotherapy is not yet understood. Methods In 200 consecutively recruited lung cancer patients (70 female, mean age 62y; mean BMI 25 kg/m2; median follow-up 15.97 months) with routine staging-CT before and after chemotherapy (CTX, mean interval: 4.3 months), densitometric quantification of total (TFA), visceral (VFA), and subcutaneous-fat-area (SFA), inter-muscular-fat-area (IMFA), muscle-density (MD), muscle-area (MA) and skeletal-muscle-index (SMI) was performed retrospectively to evaluate changes under chemotherapy and the impact on survival. Results We observed increases in TFA, VFA, SFA, VFA/SFA, and IMFA (p<0.05–0.001), while there were decreases in MA, MD and BMI (p<0.05–0.001) after chemotherapy. High pre-therapeutic VFA/SFA was a predictive factor for poor survival (HR = 1.272; p = 0.008), high pre-therapeutic MD for improved survival (HR = 0.93; p<0.05). Decrease in BMI (HR = 1.303; p<0.001), weight (HR = 1.067; p<0.001) and SMI (HR = 1.063; p<0.001) after chemotherapy were associated with poor survival. Patients with ≥4 CTX-cycles showed increased survival (17.6 vs. 9.1months), less muscle depletion (SMIdifference: p<0.05) and no BMI loss (BMIdifference: p<0.001). Conclusions After chemotherapy, patients exhibited sarcopenia with decreased muscle and increased adipose tissue compartments, which was not adequately mirrored by BMI and weight loss but by imaging. Particularly sarcopenic patients received less CTX-cycles and had poorer survival. As loss of BMI, weight and muscle were associated with poor survival, early detection (via imaging) and prevention (via physical exercise and nutrition) of sarcopenia may potentially improve outcome and reduce chemotherapy-induced toxicity. PMID

  3. Clinical Study of S-1 Plus Oxaliplatin Versus S-1 Plus Cisplatin as First-Line Treatment for Elderly Patients with Advanced Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Deng-feng BO

    2015-12-01

    Full Text Available Abstract Objective: To explore the efficacy and safety of S-1 plus oxaliplatin versus S-1 plus cisplatin as the first-line treatment for elderly patients with advanced gastric cancer. Methods: A total of 60 patients with advanced gastric cancer admitted in Xi’an Yanliang Railway Hospital from Jan., 2011 to Oct., 2013 were selected as study objects and randomly divided into 2 groups: S1 plus oxaliplatin group (SOX group, 30 cases and S1 plus cisplatin group (SP group, 30 cases. SOX group were given intravenous drip of 130 mg/m2 oxaliplatin for 2 h on d1. And S-1 was also given according to body surface area: body surface area <1.25 m2, 40 mg once; 1.25-1.5 m2, 60 mg once; >1.5, 28 d as 1 cycle. SP group was administered with intravenous drip of 25 mg/m2 cisplatin during d1-d3. Treatment was discontinued until the occurrence of disease progression or patients’ intolerance to chemotherapy. Results: SOX group was non-inferior to SP group in overall response rate (ORR (53.3% vs. 43.3%, disease control rate (DCR (83.3% vs. 80.0%, median progression-free survival (PFS (7.0 vs. 6.0 months and median overall survival (OS (11.0 vs. 10.5 months. However, the difference was statistical significant in the rate of increased KPS score (86.7% vs. 46.7%, χ2=10.800, P=0.001 and the rate of increased FACT-G score (73.3% vs. 36.7%, χ2=8.148, P=0.004. The main toxic and side effects of two groups was hematological toxicity. There was no degree III-IV toxic and side effects occurring in non hematological toxicity in two groups. The main toxic effect was peripheral neuritis in SOX group, and nausea and vomiting and renal dysfunction in SP group, and there were statistical differences in the above toxic and side effects between two groups (P<0.05. Conclusion: SOX regimen is as safe and effective as SP regimen for elderly patients with advanced gastric cancer, with better quality of life and less toxic and side effects.

  4. First-line eradication of H pylori infection in Europe: A meta-analysis based on congress abstracts, 1997-2004

    Institute of Scientific and Technical Information of China (English)

    Gy(o)rgy M Buzás; Jolán Józan

    2006-01-01

    AIM: To meta-analyse the European abstracts presented between 1997-2004 at the European H pylori Study Group, United European Gastroenterology Week meetings and World Congresses of Gastroenterology.METHODS: The abstracts of randomized/controlled prospective studies were classified into groups based on first-line eradication schedules. The quality of the abstracts was checked by a validated score system. The pooled eradication rates (PER) and combined odds ratios (OR) were calculated and compared with the published meta-analyses.RESULTS: The PER of proton pump inhibitor-based (PPI) one week triple therapies was 81.4% (confidence interval, 95% CI: 78.5-84.5). Ranitidine bismuth citratebased (RBC) triple regimens have an efficiency rate of 78.5% (95% CI: 70.5%-84.3%) (P = 0.28 vs PPI).The OR for PPI effect vs RBC regimens was 1.1 (95%CI: 0.92-1.30). H2 receptor antagonist-based triple therapies achieved 64.1% (95% CI: 52.6-75.6) (P =0.02 < 0.05 vs PPI), the OR vs PPI regimens was 1.55(95% CI: 0.72-3.78). PPI-based double combinations were less efficient than triple regimens (PER: 55.0%,OR: 4.90, 95% CI: 2.36-9.70). Quadruple regimens were successful in 82.6% (95% CI: 76.0-89.7), the OR vs triple therapies was 0.80 (0.62-1.03). Clarithromycin +amoxicillin or nitroimidazole combinations were efficient in 80.5% (95% CI: 77.2-84.2) and 83.8% (95% CI:81.7-85.9), respectively. Amoxicillin + nitromidazole therapies eradicated the infection in 73.5% (66.6-78.5) (P = 0.01 < 0.05 vs clarithromycin-based regimens).CONCL JSION: PPI/RBC-based triple therapies achieved comparable results with the meta-analyses. H2-receptor antagonists and PPI-based double combinations were less efficient. Triple and quadruple regimens were equally effective. Clarithromycin + either amoxicillin or nitroimidazole containing regimens were more effective than amoxicillin + nitroimidazole combinations. High quality congress abstracts constitutes a valuable pool of data which is suitable for meta

  5. Changes in first-line injectable disease-modifying therapy for multiple sclerosis: predictors of non-adherence, switching, discontinuation, and interruption of drugs.

    Science.gov (United States)

    Degli Esposti, Luca; Piccinni, Carlo; Sangiorgi, Diego; Perrone, Valentina; Aledda, Lucia; Marrosu, Maria Giovanna; Lombardo, Fabio

    2017-01-11

    This study was aimed to describe changes of Disease-Modifying Treatments (DMT) in an Italian cohort of patients with multiple sclerosis (MS) and to identify predictors of therapeutic modifications. Patients with MS and treated with the first-line injectable DMT (interferons-IFNs or glatiramer) between 1/7/2009 and 31/10/2012 were selected from administrative databases of the MS Center of Cagliari (Sardinia, Italy). Socio-demographic, therapeutic, and clinical information was collected in the 6 months preceding the index date. All patients were followed for 36 months to evaluate therapeutic changes in terms of non-adherence, switch, temporary discontinuation, and permanent interruption. Predictors of changes were estimated by multivariable regression models. Data on 1698 patients were collected: glatiramer was prescribed in 27% of cases, IFNβ-1b in 22%, IFNβ-1a-im in 20%, IFNβ-1a-sc-44mcg in 19%, and IFNβ-1a-sc-22mcg in 12%. Non-adherence was observed in 25% of cases, therapeutic switch in 30%, discontinuation in 37%, and permanent interruption in 28%. The risk of non-adherence was higher for IFNβ-1b, compared with IFNβ-1a-im (adjOR = 1.73). Therapeutic switch occurred especially in patients recently diagnosed (each year from diagnosis causes a decrease of this risk adjHR = 0.97); the risk of discontinuation was higher with EDSS = 4-6 and 7-9 (adjHR = 1.52 and 4.42, respectively). The risk of permanent interruption increased with the augmentation of disability (adjHR = 1.67 and 5.43 for EDSS 4-6 and 7-9). This study mirrored a detailed framework of DMT prescription and identified factors related to changes in the MS therapy. These findings could support healthcare providers in the evaluation and maximization of benefits associated with a long-term DMT.

  6. A phase II trial of docetaxel and erlotinib as first-line therapy for elderly patients with androgen-independent prostate cancer

    Directory of Open Access Journals (Sweden)

    Green Erica

    2007-07-01

    Full Text Available Abstract Background Docetaxel is the standard first-line agent for the treatment of androgen-independent prostate cancer (AIPC. The combination of docetaxel with molecularly targeted therapies may offer the potential to increase the efficacy and decrease the toxicity of cytotoxic chemotherapy for prostate cancer. Previous studies demonstrate activation of the human epidermal growth factor receptor (EGFR in prostate cancer. Erlotinib is a specific inhibitor of the tyrosine-kinase activity of EGFR. The goal of this study is to determine the anti-cancer activity docetaxel combined with erlotinib for the treatment of elderly subjects with AIPC. Methods This is a multi-institutional Phase II study in patients with histologically confirmed adenocarcinoma of the prostate and age ≥ 65 years. Patients were requred to have progressive disease despite androgen-deprivation therapy as determined by: (1 measurable lesions on cross-sectional imaging; (2 metastatic disease by radionucleotide bone imaging; or (3 elevated prostate specific antigen (PSA. Treatment cycles consisted of docetaxel 60 mg/m2 IV on day 1 and erlotinib 150 mg PO days 1–21. Patients with responding or stable disease after 9 cycles were eligible to continue on erlotinib alone as maintenance therapy. Results Characteristics of 22 patients enrolled included: median age 73.5 years (range, 65–80; median Karnofsky Performance Status 90 (range 70–100; median hemoglobin 12.1 g/dl (range, 10.0–14.3; median PSA 218.3 ng/ml (range, 9–5754. A median of 6 treatment cycles were delivered per patient (range 1–17. No objective responses were observed in 8 patients with measurable lesions (0%, 95% CI 0–31%. Bone scan improvement and PSA decline was seen in 1 patient (5%, 95% CI 0.1–25%. Five of 22 patients experienced ≥ 50 % decline in PSA (23%, 95% CI 8–45%. Hematologic toxicity included grade 3 neutropenia in 9 patients and neutropenic fever in 2 patients. Common non

  7. Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

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    Isla D

    2016-12-01

    342.57–881.29 per patient.Conclusion: In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system. Keywords: adverse event, afatinib, cost analysis, erlotinib, non-small cell lung cancer

  8. Costs of adverse events associated with erlotinib or afatinib in first-line treatment of advanced EGFR-positive non-small cell lung cancer

    Science.gov (United States)

    Isla, Dolores; De Castro, Javier; Juan, Oscar; Grau, Santiago; Orofino, Javier; Gordo, Rocío; Rubio-Terrés, Carlos; Rubio-Rodríguez, Darío

    2017-01-01

    Objectives Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are an established treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. According to published meta-analyses, no significant efficacy differences have been demonstrated between erlotinib and afatinib. However, the incidence of EGFR–TKI-related adverse events (AEs) was lower with erlotinib. This study compares the cost of management of the AEs associated with these two drugs from the perspective of the Spanish National Health System (NHS). Methods The frequency of AEs was established from a recently published meta-analysis. In Spain, the daily cost of both drugs can be considered similar; as a result, only the costs of management of the AEs were considered. Costs and resource utilization in the management of the AEs were estimated by a panel of Spanish oncologists and from studies previously carried out in Spain. A probabilistic analysis was performed based on a Monte Carlo simulation. Results The model generated 1,000 simulations. The total cost per patient treated with erlotinib and afatinib was €657.44 and €1,272.15, respectively. With erlotinib, the cost per patient and per AE of grades ≤2 and ≥3 was €550.86 and €106.58, respectively, whereas the cost with afatinib was €980.63 and €291.52, respectively. The reduction in the number of AEs with erlotinib could avoid a mean cost for the NHS of €614.71 (95% CI: €342.57–881.29) per patient. Conclusion In advanced EGFR mutation-positive NSCLC patients, first-line treatment with erlotinib could reduce health care costs for the NHS, due to a decrease in the AE rate compared with afatinib. In long-term treatments, the avoidance of complications and the lowering of costs associated with the management of AEs are relevant factors that contribute to the sustainability of the health system. PMID:28115857

  9. USE OF A COMBINATION OF АVASTIN AND LOW-DOSE INTERFERON- α IN THE FIRST-LINE TREATMENT OF METASTATIC RENAL-CELL CANCER

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    A. S. Kalpinsky

    2013-01-01

    Full Text Available Background. The registered AVOREN Phase III trial demonstrated the efficacy of a combination of bevacizumab and interferon-α (IFN-α as first-line targeted therapy in patients with metastatic renal-cell cancer (mRCC. The median progression-free survival (PFS was significantly higher in the bevacizumab + IFN-α group, amounting to 10.2 months versus 5.4 months in the IFN-α group (p < 0.0001. The most common grade 3 and 4 side effects in the AVOREN study included the adverse events due to IFN-α use; this initiated a prospective multicenter BEVLiN (Bevacizumab and Low-Dose Interferon Phase II trial in 2008 to evaluate the efficacy and tolerability of a combination of bevacizumab and low-dose IFN-α in patients with mRCC to diminish the toxicity of treatment.Subjects and methods. The trial enrolled 146 patients having good and moderate prognosis according to the MSKCC scale. The patients received Avastin 10 mg/kg every 2 weeks and IFN-α 3,000,000 IU thrice weekly. The historical control group was taken from the AVOREN trial as a control group. The main purposes of the trial were to evaluate the tolerability of treatment (the frequency of adverse events due to IFN-α use, grade 3 or more toxicity and PFS. The additional goals were to estimate overall survival (OS, objective response rates, and the incidence of any adverse events of grade 3–4 toxicity.Results. The median follow-up was 29.4 months (range 1.5–35.4 months. The rate of objective responses was 28.8 % (95 % confidence interval (CI 21.4–37.1. The median PFS was 15.3 months (95 % CI 11.7–18.0 and PFS was 58.2 and 28.9 % at 12 and 24 months of treatment, respectively. The median OS was 30.7 months (95 % CI 25.7 was unachieved. In the IFN-α group, all grades of adverse reactions and their grade 3 or more were recorded in 53.4 and 10.3 % of the patients, respectively. The adverse events that were a reason for IFN-α discontinuation were recorded in 24.0 % of the patients

  10. USE OF A COMBINATION OF АVASTIN AND LOW-DOSE INTERFERON- α IN THE FIRST-LINE TREATMENT OF METASTATIC RENAL-CELL CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Kalpinsky

    2014-07-01

    Full Text Available Background. The registered AVOREN Phase III trial demonstrated the efficacy of a combination of bevacizumab and interferon-α (IFN-α as first-line targeted therapy in patients with metastatic renal-cell cancer (mRCC. The median progression-free survival (PFS was significantly higher in the bevacizumab + IFN-α group, amounting to 10.2 months versus 5.4 months in the IFN-α group (p < 0.0001. The most common grade 3 and 4 side effects in the AVOREN study included the adverse events due to IFN-α use; this initiated a prospective multicenter BEVLiN (Bevacizumab and Low-Dose Interferon Phase II trial in 2008 to evaluate the efficacy and tolerability of a combination of bevacizumab and low-dose IFN-α in patients with mRCC to diminish the toxicity of treatment.Subjects and methods. The trial enrolled 146 patients having good and moderate prognosis according to the MSKCC scale. The patients received Avastin 10 mg/kg every 2 weeks and IFN-α 3,000,000 IU thrice weekly. The historical control group was taken from the AVOREN trial as a control group. The main purposes of the trial were to evaluate the tolerability of treatment (the frequency of adverse events due to IFN-α use, grade 3 or more toxicity and PFS. The additional goals were to estimate overall survival (OS, objective response rates, and the incidence of any adverse events of grade 3–4 toxicity.Results. The median follow-up was 29.4 months (range 1.5–35.4 months. The rate of objective responses was 28.8 % (95 % confidence interval (CI 21.4–37.1. The median PFS was 15.3 months (95 % CI 11.7–18.0 and PFS was 58.2 and 28.9 % at 12 and 24 months of treatment, respectively. The median OS was 30.7 months (95 % CI 25.7 was unachieved. In the IFN-α group, all grades of adverse reactions and their grade 3 or more were recorded in 53.4 and 10.3 % of the patients, respectively. The adverse events that were a reason for IFN-α discontinuation were recorded in 24.0 % of the patients

  11. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands.

    Science.gov (United States)

    Verduyn, S Cora; Biesma, Bonne; Schramel, Franz M N H; van der Scheer, Feike W; Langenfeld, Merel K; de Peuter, Maria A; Dingemans, Anne-Marie C

    2012-09-10

    health care setting, the previously established progression free survival benefit of first-line gefitinib in advanced NSCLC EGFR M+ patients in comparison to standard doublet chemotherapy is further supported by the Quality Adjusted PFS, which takes into account the additional health-related quality of life benefits of gefitinib over doublet chemotherapy.

  12. Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study

    Science.gov (United States)

    Bajetta, E; Di Bartolomeo, M; Buzzoni, R; Mariani, L; Zilembo, N; Ferrario, E; Lo Vullo, S; Aitini, E; Isa, L; Barone, C; Jacobelli, S; Recaldin, E; Pinotti, G; Iop, A

    2007-01-01

    This randomised phase II study evaluates the safety and efficacy profile of uracil/tegafur/leucovorin combined with irinotecan (TEGAFIRI) or with oxaliplatin (TEGAFOX). One hundred and forty-three patients with measurable, non-resectable metastatic colorectal cancer were randomised in a multicentre study to receive TEGAFIRI (UFT 250 mg m−2 day days 1–14, LV 90 mg day days 1–14, irinotecan 240 mg m−2 day 1; q21) or TEGAFOX (UFT 250 mg m−2 day days 1–14, LV 90 mg day days 1–14, oxaliplatin 120 mg m−2 day 1; q21). Among 143 randomised patients, 141 were analysed (68 received TEGAFIRI and 73 TEGAFOX). The main characteristics of the two arms were well balanced. The most common grade 3–4 treatment-related adverse events were neutropenia (13% of cases with TEGAFIRI; 1% in the TEGAFOX group). Diarrhoea was prevalent in the TEGAFIRI arm (16%) vs TEGAFOX (4%). Six complete remission (CR) and 19 partial remission (PR) were recorded in the TEGAFIRI arm (odds ratio (OR): 41.7; 95% confidence limit (CL), 29.1–55.1%), and six CR and 22 PR were recorded in the TEGAFOX group, (OR: 38.9; 95% CL, 27.6–51.1). At a median time follow-up of 17 months (intequartile (IQ) range 12–23), a median survival probability of 20 and 19 months was obtained in the TEGAFIRI and TEGAFOX groups, respectively. Median time to progression was 8 months for both groups. TEGAFIRI and TEGAFOX are both effective and tolerable first-line therapies in MCRC patients. The employment of UFT/LV given in doublet combination is interesting and the presented data appear comparable to equivalent infusion regimens described in the literature. The safety profile of the two combinations also allows an evaluation with other biological agents such as monoclonal antibodies. PMID:17245343

  13. Clinical Significance of Early Changes in Circulating Tumor Cells from Patients Receiving First-Line Cisplatin-Based Chemotherapy for Metastatic Urothelial Carcinoma1

    Science.gov (United States)

    Fina, Emanuela; Necchi, Andrea; Giannatempo, Patrizia; Colecchia, Maurizio; Raggi, Daniele; Daidone, Maria Grazia; Cappelletti, Vera

    2016-01-01

    Background: The therapeutic paradigm of metastatic urothelial carcinoma (UC) is rapidly shifting and new biomarkers are needed to enhance patient selection. Objective: Early identification of dynamic predictors of outcome may be a key to optimize the sequence of effective therapies in metastatic UC patients. Methods: Blood samples from patients receiving first-line MVAC chemotherapy were collected at baseline (T0) and after 2 cycles (T2). Samples were processed by immunomagnetic beads (AdnaTest ProstateCancerSelect kit) and the expression of EPCAM, MUC1 and ERBB2 was studied using multiplex-PCR. Circulating tumor cell (CTC) positivity and cutoffs, obtained by receiver operator characteristic (ROC) curve analysis in healthy donors, were: ≥1 positive marker among EPCAM (≥0.40 ng/μl), MUC1 (≥0.10 ng/μl) and ERBB2 (≥0.20 ng/μl). CTC variation (T0/T2) was split in favorable (+/–, –/–, –/+) and unfavorable groups (+/+). Cox regression analyses evaluated associations with clinical factors. Results: In this pilot study to assess a new CTC detection method, among 31 evaluable patients, 17 (54.8%) were CTC-positive at T0. No association was found between CTC and objective response to MVAC. CTC dynamic changes better predicted 3-year progression-free (PFS) and overall survival (OS) compared to CTC status assessed at single time points. Unfavorable trend was univariably detrimental on 3-year PFS (10% vs. 49.2%, p = 0.006) and OS (20% vs. 63.5%, p = 0.017). Significance was maintained after controlling for liver metastases (p = 0.031 and p = 0.025 for PFS and OS) and MSKCC score (p = 0.014 and 0.025). Conclusions: Newly described early CTC changes during chemotherapy might be useful to improve our prognostic ability. Pending validation, these results could fulfill the promise to help accelerating therapeutic sequences. PMID:28035320

  14. Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab.

    Science.gov (United States)

    Formica, Vincenzo; Palmirotta, Raffaele; Del Monte, Girolamo; Savonarola, Annalisa; Ludovici, Giorgia; De Marchis, Maria Laura; Grenga, Italia; Schirru, Michele; Guadagni, Fiorella; Roselli, Mario

    2011-02-01

    The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients. Forty MCRC patients eligible for a first-line therapy were enrolled in this prospective trial and treated with FOLinate/Fluorouracil/Irinotecan (FOLFIRI) + Bev (male/female = 22:18, age (median) = 61 years). Eight VGPs within the promoter/5'UTR region were evaluated in patient blood samples. Primary endpoint was association between VGPs and median progression-free survival (mPFS). Overall radiological response rate (ORR), overall survival (OS), and toxicity were assessed as secondary outcomes. VGPs -2578, -1512, -1451, -1411, and -460 were in complete linkage disequilibrium and therefore analyzed as haplotype (two variants: Haplo1: A-18 bp insertion-T-4G-C and Haplo2: C-18 bp deletion-C-5G-T, respectively). Seventeen patients Haplo2/Haplo2 had significantly shorter mPFS compared to 23 patients Haplo1/Haplo1 or Haplo1/Haplo2 (mPFS, 9 vs. 15.4 months, respectively, p = 0.02; hazard ratio (HR), 2.64). Also, VGPs -152 (G/G vs. G/A + A/A) and -1154 (G/G vs. G/A + A/A) were significantly associated with PFS (mPFS, 8.9 vs. 15.4 months, p = 0.007; HR, 3.53 and 9.8 vs. 16 months, p = 0.03, HR, 2.32, respectively). In the multivariate analysis including also biochemical variables known to influence prognosis, VGP -1154 retained an independent predictive value for mPFS (G/G over G/A + A/A = HR, 4.43; p = 0.02). With regard to ORR, only VGP -634 was significantly associated with response (G/G vs. G/C + C/C = 64% vs. 14%, p = 0.03). No significant influence on OS and toxicity by the investigated VGPs was observed. Although these data need to be confirmed in larger trials, investigation of germline VGPs may help identify patients who are more sensitive to anti-VEGF agents.

  15. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    Venook, Alan P.; Niedzwiecki, Donna; Lenz, Heinz-Josef; Innocenti, Federico; Fruth, Briant; Meyerhardt, Jeffrey A.; Schrag, Deborah; Greene, Claire; O’Neil, Bert H.; Atkins, James Norman; Berry, Scott; Polite, Blase N.; O’Reilly, Eileen M.; Goldberg, Richard M.; Hochster, Howard S.; Schilsky, Richard L.; Bertagnolli, Monica M.; El-Khoueiry, Anthony B.; Watson, Peter; Benson, Al B.; Mulkerin, Daniel L.; Mayer, Robert J.; Blanke, Charles

    2017-01-01

    IMPORTANCE Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. OBJECTIVE To determine if the addition of cetuximab vsbevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. INTERVENTIONS Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. MAIN OUTCOMES AND MEASURES The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. RESULTS Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0–110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77–1.01; P = .08). The

  16. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

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    Jonathan González García

    2017-01-01

    Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

  17. 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6 plus sunitinib or bevacizumab as first-line treatment for metastatic colorectal cancer: a randomized Phase IIb study

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    Hecht JR

    2015-06-01

    Full Text Available J Randolph Hecht,1 Edith P Mitchell,2 Takayuki Yoshino,3 Manfred Welslau,4 Xun Lin,5 Edna Chow Maneval,6 Jolanda Paolini,7 Maria Jose Lechuga,7 Albrecht Kretzschmar8  1David Geffen School of Medicine at UCLA, Santa Monica, CA, 2Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, USA; 3National Cancer Center Hospital East, Chiba, Japan; 4Onkologische Praxis Klausmann/Welslau, Aschaffenburg, Germany; 5Pfizer Oncology, La Jolla, 6Seragon Pharmaceuticals, San Diego, CA, USA; 7Pfizer Oncology, Milan, Italy; 8Klinikum St Georg, Leipzig, Germany Background: Sunitinib is an oral inhibitor of tyrosine kinase receptors implicated in tumor proliferation, angiogenesis, and metastasis. In this randomized, multicenter, open-label Phase IIb study, sunitinib plus mFOLFOX6 (oxaliplatin plus leucovorin plus 5-fluorouracil was compared with bevacizumab plus mFOLFOX6 as first-line therapy in patients with metastatic colorectal cancer. Methods: Patients were stratified by performance status, baseline lactate dehydrogenase level, and prior adjuvant treatment, and randomized 1:1 to receive sunitinib 37.5 mg/day for 4 weeks on and 2 weeks off plus mFOLFOX6 every 2 weeks or bevacizumab 5 mg/kg every 2 weeks plus mFOLFOX6 every 2 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, overall survival, safety, and quality of life. Results: Enrollment was closed early following accrual of 191 patients, based on an interim analysis showing an inferior trend in the primary progression-free survival efficacy endpoint for sunitinib. Ninety-six patients were randomized to sunitinib plus mFOLFOX6 and 95 to bevacizumab plus mFOLFOX6. Median progression-free survival was 9.3 months and 15.4 months, respectively, but the objective response rate was similar between the study arms. Median overall survival was 23.7 months and 34.1 months, respectively. Dose reductions and interruptions were more common with

  18. Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

    Science.gov (United States)

    Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

    2012-01-01

    Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to

  19. The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis.

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    Han Yan

    Full Text Available The combination of chemotherapy and epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC. This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL, Chinese biomedical literature database (CNKI and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.A total of six randomized controlled trials (RCTs including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS, time to progression (TTP and objective response rate (ORR, compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98-1.12; TTP: HR = 0.94, 95%CI = 0.89-1.00; ORR: RR = 1.07, 95%CI = 0.98-1.17, and no significant difference in OS and progression-free survival (PFS, compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83-1.46; PFS: HR = 0.86, 95% CI = 0.67-1.10. The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10-1.79 and rash (RR = 7.43, 95% CI = 4.56-12.09, compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25-35.93 and fatigue (RR = 9.60, 95% CI = 2.28-40.86 compared with EGFR TKI monotherapy.The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC.

  20. Retrospective exploratory analysis of VEGF polymorphisms in the prediction of benefit from first-line FOLFIRI plus bevacizumab in metastatic colorectal cancer

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    Manzoni Mariangela

    2011-06-01

    Full Text Available Abstract Background Molecular predictors of bevacizumab efficacy in colorectal cancer have not been identified yet. Specific VEGF polymorphisms may affect gene transcription and therefore indirectly influence the efficacy of bevacizumab. Methods Genomic DNA of 111 consecutive metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab was obtained from blood samples. VEGF -2578 C/A, -1498 C/T, + 405 C/G, + 936 C/T polymorphisms were analyzed by means of PCR-RFLP. DNA samples from 107 patients treated with FOLFIRI alone served as historical control group. The relation of VEGF polymorphisms with PFS, evaluated through Kaplan-Meier method and log-rank test, was the primary end-point. An interaction test with a Cox model has been performed in order to demonstrate the heterogeneity of the effect of VEGF -1498 C/T polymorphism between bevacizumab-and control group. Results In the bevacizumab-group median PFS and OS of patients carrying VEGF -1498 C/C, C/T and T/T allelic variants were, respectively, 12.8, 10.5, 7.5 months (p = 0.0046, log-rank test and 27.3, 20.5, 18.6 months (p = 0.038, log-rank test. VEGF -1498 T/T genotype was associated with shorter PFS (HR = 2.13, [1.41-5.10], p = 0.0027. In the control group no significant association of VEGF -1498 C/T allelic variants and PFS or OS was found. Interaction between VEGF -1498 C/T variants and treatment effect suggested that the relation of VEGF -1498 T/T genotype with shorter PFS was caused by the effect of bevacizumab (p = 0.011. Other investigated polymorphisms did not affect the outcome. Conclusions These data suggest a possible role for VEGF -1498 C/T variants in predicting the efficacy of bevacizumab in the up-front treatment of metastatic colorectal cancer patients. A molecular tool for selecting subjects candidate to benefit from the anti-VEGF could be important for clinical practice. The retrospective and exploratory design of the present study, coupled with the

  1. Value of Tropheryma whipplei quantitative polymerase chain reaction assay for the diagnosis of Whipple disease: usefulness of saliva and stool specimens for first-line screening.

    Science.gov (United States)

    Fenollar, Florence; Laouira, Sonia; Lepidi, Hubert; Rolain, Jean-Marc; Raoult, Didier

    2008-09-01

    Whipple disease (WD) is a chronic infectious disease caused by Tropheryma whipplei. WD DNA has been found in stool and saliva specimens from patients and asymptomatic carriers. A total of 4418 samples that were sent to our center for determination of WD were tested by a T. whipplei-specific quantitative polymerase chain reaction (PCR) based on repetitive sequences. Definite WD was diagnosed in 71 patients, including 55 patients with classic WD (defined by positive results of periodic acid-Schiff staining and/or specific immunohistochemistry of small-bowel biopsy specimens) and 16 patients with localized WD (including patients with endocarditis, neurologic infection, and uveitis). Of the persons without WD, 2.3% had stool specimens positive for T. whipplei by PCR and 0.2% had saliva specimens positive for T. whipplei by PCR. Diagnosis of WD was likely in patients with positive results of both PCR of saliva specimens and PCR of stool specimens (positive predictive value, 95.2%). When the bacterial load was >10(4) colony-forming units per g of stool, the positive predictive value was 100%. A negative result of PCR of a saliva or stool specimen had a negative predictive value of 99.2% for classic WD. For localized WD, positive results of both PCR of saliva specimens and PCR of stool specimens had a sensitivity of 58% (compared with 94% for classic WD). The positive predictive value of testing of blood, cerebrospinal fluid, and urine specimens was 100% for each, and the positive predictive value for testing of duodenal biopsy specimens was 97.5%. T. whipplei-specific quantitative PCR of saliva and stool specimens should be performed as first-line noninvasive screening for WD. When the results for both types of specimens are positive, diagnosis of classic WD should be highly suspected, especially if a high bacterial load is detected. Because PCR of saliva and stool specimens lacks sensitivity for determination of localized WD, invasive samples should be tested on the

  2. Economic implications of using bendamustine, alemtuzumab, or chlorambucil as a first-line therapy for chronic lymphocytic leukemia in the US: a cost-effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Kongnakorn T

    2014-04-01

    Full Text Available Thitima Kongnakorn,1 James A Sterchele,2 Christopher G Salvador,3 Denis Getsios,4 Mkaya Mwamburi51Evidera, Bangkok, Thailand; 2formerly of Teva Branded Pharmaceutical Products R&D, Inc, Frazer, PA, 3Oncology Market Research, Teva Branded Pharmaceutical Products R&D, Inc, Frazer, PA, 4Evidera, Lexington, MA, 5Tufts University School of Medicine, Public Health and Community Medicine, Boston, MA, USABackground: The objective of this analysis was to evaluate the cost-effectiveness of using bendamustine versus alemtuzumab or bendamustine versus chlorambucil as a first-line therapy in patients with Binet stage B or C chronic lymphocytic leukemia (CLL in the US.Methods: A discrete event simulation of the disease course of CLL was developed to evaluate the economic implications of single-agent treatment with bendamustine, alemtuzumab, or chlorambucil, which are indicated for a treatment-naïve patient population with Binet stage B or C CLL. Data from clinical trials were used to create a simulated patient population, risk equations for progression-free survival and survival post disease progression, response rates, and rates of adverse events. Costs from a US health care payer perspective in 2012 US dollars, survival (life years, and quality-adjusted life years (QALYs were estimated over a patient's lifetime; all were discounted at 3% per year.Results: Compared with alemtuzumab, bendamustine was considered to be a dominant treatment providing greater benefit (6.10 versus 5.37 life years and 4.02 versus 3.45 QALYs at lower cost ($78,776 versus $121,441. Compared with chlorambucil, bendamustine was associated with higher costs ($78,776 versus $42,337 but with improved health outcomes (6.10 versus 5.21 life years and 4.02 versus 3.30 QALYs, resulting in incremental cost-effectiveness ratios of $40,971 per life year gained and $50,619 per QALY gained.Conclusion: Bendamustine is expected to provide cost savings and greater health benefit than alemtuzumab in

  3. Computing the modal mass from the state space model in combined experimental-operational modal analysis

    Science.gov (United States)

    Cara, Javier

    2016-05-01

    Modal parameters comprise natural frequencies, damping ratios, modal vectors and modal masses. In a theoretic framework, these parameters are the basis for the solution of vibration problems using the theory of modal superposition. In practice, they can be computed from input-output vibration data: the usual procedure is to estimate a mathematical model from the data and then to compute the modal parameters from the estimated model. The most popular models for input-output data are based on the frequency response function, but in recent years the state space model in the time domain has become popular among researchers and practitioners of modal analysis with experimental data. In this work, the equations to compute the modal parameters from the state space model when input and output data are available (like in combined experimental-operational modal analysis) are derived in detail using invariants of the state space model: the equations needed to compute natural frequencies, damping ratios and modal vectors are well known in the operational modal analysis framework, but the equation needed to compute the modal masses has not generated much interest in technical literature. These equations are applied to both a numerical simulation and an experimental study in the last part of the work.

  4. It does belong together: Cross-modal correspondences influence cross-modal integration during perceptual learning

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    Lionel eBrunel

    2015-04-01

    Full Text Available Experiencing a stimulus in one sensory modality is often associated with an experience in another sensory modality. For instance, seeing a lemon might produce a sensation of sourness. This might indicate some kind of cross-modal correspondence between vision and gustation. The aim of the current study was to provide explore whether such cross-modal correspondences influence cross-modal integration during perceptual learning. To that end, we conducted 2 experiments. Using a speeded classification task, Experiment 1 established a cross-modal correspondence between visual lightness and the frequency of an auditory tone. Using a short-term priming procedure, Experiment 2 showed that manipulation of such cross-modal correspondences led to the creation of a crossmodal unit regardless of the nature of the correspondence (i.e., congruent, Experiment 2a or incongruent, Experiment 2b. However, a comparison of priming-effects sizes suggested that cross-modal correspondences modulate cross-modal integration during learning and thus leading to new learned units that have different stability over time. We discuss the implications of our results for the relation between cross-modal correspondence and perceptual learning in the context of a Bayesian explanation of cross-modal correspondences.

  5. It does belong together: cross-modal correspondences influence cross-modal integration during perceptual learning.

    Science.gov (United States)

    Brunel, Lionel; Carvalho, Paulo F; Goldstone, Robert L

    2015-01-01

    Experiencing a stimulus in one sensory modality is often associated with an experience in another sensory modality. For instance, seeing a lemon might produce a sensation of sourness. This might indicate some kind of cross-modal correspondence between vision and gustation. The aim of the current study was to explore whether such cross-modal correspondences influence cross-modal integration during perceptual learning. To that end, we conducted two experiments. Using a speeded classification task, Experiment 1 established a cross-modal correspondence between visual lightness and the frequency of an auditory tone. Using a short-term priming procedure, Experiment 2 showed that manipulation of such cross-modal correspondences led to the creation of a crossmodal unit regardless of the nature of the correspondence (i.e., congruent, Experiment 2a or incongruent, Experiment 2b). However, a comparison of priming effects sizes suggested that cross-modal correspondences modulate cross-modal integration during learning, leading to new learned units that have different stability over time. We discuss the implications of our results for the relation between cross-modal correspondence and perceptual learning in the context of a Bayesian explanation of cross-modal correspondences.

  6. Determination of rolling tyre modal parameters using Finite Element techniques and Operational Modal Analysis

    Science.gov (United States)

    Palanivelu, Sakthivel; Narasimha Rao, K. V.; Ramarathnam, Krishna Kumar

    2015-12-01

    In order to address various noise generation mechanisms and noise propagation phenomena of a tyre, it is necessary to study the tyre dynamic behaviour in terms of modal parameters. This paper enumerates a novel method of finding the modal parameters of a rolling tyre using an Explicit Finite Element Analysis and Operational Modal Analysis (OMA). ABAQUS Explicit, a commercial Finite Element (FE) software code has been used to simulate the experiment, a tyre rolling over a semi-circular straight and inclined cleat. The acceleration responses obtained from these simulations are used as input to the OMA. LMS test lab has been used for carrying out the Operational Modal Analysis. The modal results are compared with the published results of Kindt [22] and validated. Also, the modal results obtained from OMA are compared with FE modal results of stationary unloaded tyre, stationary loaded tyre and Steady State Transport rolling tyre.

  7. NIF Periscope Wall Modal Study Comparison of Results for 2 FEA Models with 2 Modal Tests

    Energy Technology Data Exchange (ETDEWEB)

    Eli, M W; Gerhard, M A; Lee, C L; Sommer, S C; Woehrle, T G

    2000-10-26

    This report summarizes experimentally and numerically determined modal properties for one of the reinforced concrete end walls of the NIF Periscope Support Structure in Laser Bay 1. Two methods were used to determine these modal properties: (1) Computational finite-element analyses (modal extraction process); and (2) Experimental modal analysis based on measured test data. This report also includes experimentally determined modal properties for a prototype LM3/Polarizer line-replaceable unit (LRU) and a prototype PEPC LRU. Two important parameters, used during the design phase, are validated through testing [ref 1]. These parameters are the natural frequencies and modal damping (of the system in question) for the first several global modes of vibration. Experimental modal testing provides these modal values, along with the corresponding mode shapes. Another important parameter, the input excitation (expected during normal operation of the NIF laser system) [ref 1], can be verified by performing a series of ambient vibration measurements in the vicinity of the particular system (or subsystem) of interest. The topic of ambient input excitation will be covered in a separate report. Due to the large mass of the Periscope Pedestal, it is difficult to excite the entire series of Periscope Pedestal Walls all at once. It was decided that the experimental modal tests would be performed on just one Periscope End Wall in Laser Bay 1. Experimental modal properties for the Periscope End Wall have been used to validate and update the FE analyses. Results from the analyses and modal tests support the conclusion that the Periscope Pedestal will not exceed the stability budget, which is described in reference 1. The results of the modal tests for the Periscope End Wall in Laser Bay 1 have provided examples of modal properties that can be derived from future modal tests of the entire Periscope Assembly (excluding the LRU's). This next series of larger modal tests can be

  8. Conceptual structure within and between modalities

    Directory of Open Access Journals (Sweden)

    Katia eDilkina

    2013-01-01

    Full Text Available Current views of semantic memory share the assumption that conceptual representations are based on multi-modal experience, which activates distinct modality-specific brain regions. This proposition is widely accepted, yet little is known about how each modality contributes to conceptual knowledge and how the structure of this contribution varies across these multiple information sources. We used verbal feature lists, features from drawings and verbal co-occurrence statistics from latent semantic analysis to examine the informational structure in four domains of knowledge: perceptual, functional, encyclopedic and verbal. The goals of the analysis were three-fold: (1 to assess the structure within individual modalities; (2 to compare structures between modalities; and (3 to assess the degree to which concepts organize categorically or randomly.Our results indicated significant and unique structure in all four modalities: perceptually, concepts organize based on prominent features such as shape, size, color and parts; functionally, they group based on use and interaction; encyclopedically, they arrange based on commonality in location or behavior; and verbally, they group associatively or relationally. Visual/perceptual knowledge gives rise to the strongest hierarchical organization and is closest to classic taxonomic structure. Information is organized somewhat similarly in the perceptual and encyclopedic domains, which differs significantly from the structure in the functional and verbal domains. Notably, the verbal modality has the most unique organization, which is not at all categorical but also not random. The idiosyncrasy and complexity of conceptual structure across modalities begs the question of how all of these modality-specific experiences are fused together into coherent, multi-faceted yet unified concepts. Accordingly, both methodological and theoretical implications of the present findings are discussed.

  9. Vibration measurement and modal analysis for tunneller

    Institute of Scientific and Technical Information of China (English)

    HUANG Min; WU Miao; WEI Ren-zhi

    2001-01-01

    In this paper, the method of vibration measurement and modal analysis for AM~50 Tunneller machine is presented. When the machine was used for cutting man-made coal bed and real coal bed, the vibration of the machine was measured and the results of signal analysis show that the vibration characteristics under the two kinds of working situations are similar. The modal model of the machine is established, and then, the intrinsic vibration characteristics of AM50 tunneller are investigated by means of the method of experimental modal analysis. The vibration response simulation under a set of loading spectra measured is carried out by force response simulation software.

  10. Modal Wave Number Spectrum for Mesoscale Eddies

    Institute of Scientific and Technical Information of China (English)

    KANG Ying; PENG Linhui

    2003-01-01

    The variations of ocean environmental parameters invariably result in variations of local modal wave numbers of a sound pressure field. The asymptotic Hankel transform with a short sliding window is applied to the complex sound pressure field in the water containing a mesoscale eddy to examine the variation of local modal wave numbers in such a range-dependent environment. The numerical simulation results show that modal wave number spectra obtained by this method can reflect the location and strength of a mesoscale eddy, therefore it can be used to monitor the strength and spatial scale of ocean mesoscale eddies.

  11. Safety and Efficacy of First-Line Bevacizumab Plus Chemotherapy in Elderly Patients with Advanced or Recurrent Nonsquamous Non-small Cell Lung Cancer Safety of Avastin in Lung trial (MO19390)

    NARCIS (Netherlands)

    Laskin, Janessa; Crino, Lucio; Felip, Enriqueta; Franke, Fabio; Gorbunova, Vera; Groen, Harry; Jiang, Guo-liang; Reck, Martin; Schneider, Claus-Peter

    2012-01-01

    Introduction: Safety of Avastin in Lung (MO19390) was an international, open-label, single-arm study, which assessed the safety and efficacy of first-line bevacizumab (Avastin (R)) in combination with standard chemotherapy in patients (n = 2212) with advanced or recurrent non-small cell lung cancer

  12. The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer : Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Christensen, René Depont; Andersen, Rikke Fredslund;

    2012-01-01

    PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothel...

  13. Modality-Invariant Image Classification Based on Modality Uniqueness and Dictionary Learning.

    Science.gov (United States)

    Kim, Seungryong; Cai, Rui; Park, Kihong; Kim, Sunok; Sohn, Kwanghoon

    2016-12-02

    We present a unified framework for image classification of image sets taken under varying modality conditions. Our method is motivated by a key observation that the image feature distribution is simultaneously influenced by the semantic-class and the modality category label, which limits the performance of conventional methods for that task. With this insight, we introduce modality uniqueness as a discriminative weight that divides each modality cluster from all other clusters. By leveraging the modality uniqueness, our framework is formulated as unsupervised modality clustering and classifier learning based on modality-invariant similarity kernel. Specifically, in the assignment step, each training image is first assigned to the most similar cluster according to its modality. In the update step, based on the current cluster hypothesis, the modality uniqueness and the sparse dictionary are updated. These two steps are formulated in an iterative manner. Based on the final clusters, a modalityinvariant marginalized kernel is then computed, where the similarities between the reconstructed features of each modality are aggregated across all clusters. Our framework enables the reliable inference of semantic-class category for an image, even across large photometric variations. Experimental results show that our method outperforms conventional methods on various benchmarks, such as landmark identification under severely varying weather conditions, domain-adapting image classification, and RGB and near-infrared (NIR) image classification.

  14. Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation

    Directory of Open Access Journals (Sweden)

    Maggiolo F

    2015-02-01

    dominated any other therapeutic approach. Sensitivity analysis was performed, and starting right away with an STR was cost-effective even when compared with therapeutic strategies contemplating STR as simplification. Conclusion: By integrating clinical data with economic variables, our study offers an estimate of the cost-effectiveness of the various first-line treatment strategies for patients infected with HIV and provides significant evidence to be used in future prospective pharmacoeconomic evaluations. Keywords: cost-effectiveness, quality-adjusted life years, highly active antiretroviral therapy, single-tablet regimen

  15. Effectiveness of first-line antiretroviral therapy based on NNRTIs vs ritonavir-boosted PIs in HIV-1 infected patients with high plasma viral load

    Directory of Open Access Journals (Sweden)

    A Imaz

    2012-11-01

    Full Text Available Purpose of the study: Few clinical trials have compared non-nucleoside reverse transcriptase inhibitors (NNRTI and ritonavir-boosted protease inhibitors (PI/r as initial combined antiretroviral therapy (cART for HIV-1-infected patients with high plasma viral load (pVL, and non-conclusive results have been reported. We compared the effectiveness between NNRTI and PI/r as first-line cART for HIV-1-infected patients with high pVL. Methods: Observational retrospective study of 664 consecutive treatment-naïve HIV-1-infected patients with pVL (HIV-1 RNA >100,000 copies/mL who initiated NNRTI or PI/r-based cART between 2000–2010 in three University hospitals. Only currently preferred or alternative regimens in clinical guidelines were included. Primary endpoint: percentage of therapeutic failures at week 48. Virologic failure was defined as: a lack of virologic response (<1 log RNA HIV-1 decrease in first 3 months; b RNA HIV-1 >50 c/mL at week 48; c confirmed rebound >50 c/ml after a previous value <50 c/mL. Intent-to-treat (ITT noncompleter=failure and on-treatment (OT analyses were performed. Results: 62% of patients initiated NNRTI-regimens (83% efavirenz and 38% PI/r-regimens (62% lopinavir/. Baseline characteristics: male 83%; median age 39 yrs; median CD4 count: 212/µL (NNRTI 232 vs PI/r 177, p=0.028; pVL 5.83 log10 c/mL (NNRTI 5.43 vs PI/r 5.55, p=0.007; AIDS 24% (NNRTI 21% vs PI/r 29%, p=0.015. NRTI backbones were tenofovir plus 3TC or FTC in 72%. The percentage of therapeutic failure was higher in the PI/r group (ITT NC=F 26% vs 18%, p=0.012 with no differences in virologic failures (PI/r 5%, NNRTI 6%, p=0.688. The rate of treatment changes due to toxicity and/or voluntary discontinuations was higher in the PI/r group (15% vs 8%, p=0.008. A multivariate analysis adjusted for age, gender, CD4 count, VL and AIDS showed NNRTI vs PI/r as the only variable associated with treatment response (OR 0.61, 95% CI 0.41–0.88. Median pVL and rate of

  16. OPERATIONAL MODAL ANALYSIS SCHEMES USING CORRELATION TECHNIQUE

    Institute of Scientific and Technical Information of China (English)

    Zheng Min; Shen Fan; Chen Huaihai

    2005-01-01

    For some large-scale engineering structures in operating conditions, modal parameters estimation must base itself on response-only data. This problem has received a considerable amount of attention in the past few years. It is well known that the cross-correlation function between the measured responses is a sum of complex exponential functions of the same form as the impulse response function of the original system. So this paper presents a time-domain operating modal identification global scheme and a frequency-domain scheme from output-only by coupling the cross-correlation function with conventional modal parameter estimation. The outlined techniques are applied to an airplane model to estimate modal parameters from response-only data.

  17. Disentangling Linguistic Modality Effects in Semantic Processing.

    Science.gov (United States)

    Moita, Mara; Nunes, Maria Vânia

    2016-06-01

    Sensory systems are essential for perceiving and conceptualizing our semantic knowledge about the world and the way we interact with it. Despite studies reporting neural changes to compensate for the absence of a given sensory modality, studies focusing on the assessment of semantic processing reveal poor performances by deaf individuals when compared with hearing individuals. However, the majority of those studies were not performed in the linguistic modality considered the most adequate to their sensory capabilities (i.e., sign language). Therefore, this exploratory study was developed focusing on linguistic modality effects during semantic retrieval in deaf individuals in comparison with their hearing peers through a category fluency task. Results show a difference in performance between the two linguistic modalities by deaf individuals as well as in the type of linguistic clusters most chosen by participants, suggesting a complex clustering tendency by deaf individuals.