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Sample records for viable first-line treatment

  1. Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

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    Gisbert, Javier P; Barrio, Jesús; Modolell, Inés; Molina-Infante, Javier; Aisa, Angeles Perez; Castro-Fernández, Manuel; Rodrigo, Luis; Cosme, Angel; Gisbert, Jose Luis; Fernández-Bermejo, Miguel; Marcos, Santiago; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Helicobacter pylori eradication is a challenge in penicillin allergy. To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

  2. Inhaled Steroids: First Line Treatment of Adult Asthma

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    André Cartier

    1995-01-01

    Full Text Available Corticosteroids are the most potent inhaled anti-inflammatory drugs for asthma treatment. This paper reviews the clinical evidence supporting the early use of inhaled steroids in asthma as a first line treatment. Inhaled steroids can probably alter the course of asthma, especially in mild asthmatics. Once they have been shown to improve control of asthma and even if the need for beta2-agonists is virtually nil, their use should be continued at low doses (ie, equivalent to 400 to 500 μg of budesonide or beclomethasone for at least one year before attempting to reduce the dosage.

  3. Cetuximab in first line treatment of metastatic colorectal cancer

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    Carlo Barone

    2012-07-01

    Full Text Available The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI, compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to

  4. Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

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    Muneishi, Manaka; Nakamura, Ayaka; Tachibana, Katsumi; Suemitsu, Junko; Hasebe, Shinji; Takeuchi, Kazuto; Yakushijin, Yoshihiro

    2018-04-01

    Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

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

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    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

  6. First-line drugs for hypertension.

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    Wright, James M; Musini, Vijaya M; Gill, Rupam

    2018-04-18

    This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question. To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment.Secondary objectives: when different antihypertensive drug classes are used as the first-line drug, to quantify the blood pressure lowering effect and the rate of withdrawal due to adverse drug effects, compared to placebo or no treatment. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. Randomized trials (RCT) of at least one year duration, comparing one of six major drug classes with a placebo or no treatment, in adult patients with blood pressure over 140/90 mmHg at baseline. The majority (over 70%) of the patients in the treatment group were taking the drug class of interest after one year. We included trials with both hypertensive and normotensive patients in this review if the majority (over 70%) of patients had elevated blood pressure, or the trial separately reported outcome data on patients with elevated blood pressure. The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and

  7. 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...... post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....

  8. First-line treatment of acute lymphoblastic leukemia with pegasparaginase

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    Riccardo Masetti

    2009-07-01

    Full Text Available Riccardo Masetti, Andrea PessionPediatric Oncology and Hematology Unit “Lalla Seràgnoli”, University of Bologna, Bologna, ItalyAbstract: Acute lymphoblastic leukemia (ALL accounts for almost 4000 cases annually in the United States, approximately two thirds of which are in children and adolescents. Treatment results of ALL have improved considerably in the past decade, due to an optimal stratification of patients and a rational use of different antileukemic agents among which L-asparaginase (L-ASNase plays a fundamental role. This drug has been used in pediatric ALL chemotherapy protocols for almost 3 decades. In the 1970s and 1980s a chemically modified form of this enzyme called pegasparaginase (PEG-ASNase was rationally synthesized to decrease immunogenicity of the enzyme and prolong its half-life. The different advantages of PEG-ASNase have been demonstrated in many clinical studies, the last of which underline the utility of this drug in front-line therapy of ALL. In this review, we discuss the pharmacological advantages and clinical potential of PEG-ASNase and its important use in first-line treatment of ALL.Keywords: pegasparaginase, acute, lymphoblastic leukemia, pegylation

  9. The use of super-selective mesenteric embolisation as a first-line management of acute lower gastrointestinal bleeding

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    Bryan Soh, MBBS, BBiomedSci, PGDipSurgAnat

    2017-05-01

    Conclusion: Super-selective mesenteric embolisation is a viable, safe and effective first line management for localised LGIB. Our results overall compare favourably with the published experiences of other institutions. It is now accepted first-line practice at our institution to manage localised LGIB with embolisation.

  10. [First-line treatment of lymphomas of "high grade malignancy" or "aggressive lymphomas"].

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    Reyes, F

    2001-11-01

    Main strategies used as first line treatment of aggressive lymphoma are the subject of this review. The evolution of histopathlogical classifications is reviewed and the concept of aggressive lymphoma is given. General principles of chemotherapy treatment and main prognostic factors that direct therapeutic decisions are described. The treatment modalities of localized and advanced disease are detailed, as well as the role of high-dose therapy with hematopoietic support. Finally, the major impact of immunotherapy based on the monoclonal anti-CD20 antibody is envisaged.

  11. Biofeedback as a first-line treatment for overactive bladder syndrome refractory to standard urotherapy in children.

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    Ebiloglu, Turgay; Kaya, Engin; Köprü, Burak; Topuz, Bahadır; Irkilata, Hasan Cem; Kibar, Yusuf

    2016-10-01

    Overactive bladder syndrome (OAB) and dysfunctional voiding (DV) are subgroups of lower urinary tract dysfunction (LUTD). Standard urotherapy is the first-line treatment option of OAB in children. The aim was to investigate the use of biofeedback as a first-line treatment option in OAB refractory to standard urotherapy, and determine the factors affecting efficacy. Between 2005 and 2015, we retrospectively analyzed a total of 136 hospital records of children with OAB who had not previously used any anticholinergics and were refractory to standard urotherapy. Patients with urgency and/or urge incontinence and/or making holding maneuvers to suppress urgency were defined as having OAB symptoms, and resolution of these complaints was defined as successful biofeedback therapy. Seventy-three of 136 OAB patients' urgency recovered by biofeedback therapy with the success rate of 53% (p biofeedback therapies, respectively (p Biofeedback can be thought of as the first-line treatment option when standard urotherapy fails in children with OAB. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  12. Trans-catheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors

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    Roche, Alain; Girish, Baragur V.; de Baere, Thierry; Baudin, Eric; Schlumberger, Martin; Boige, Valerie; Ducreux, Michel; Elias, Dominique; Lasser, Philippe

    2003-01-01

    Our objective was to report the outcome in patients with liver metastasis from endocrine tumors who underwent transarterial chemoembolization (TACE) as first-line non-surgical treatment. From January 1990 to December 2000, 14 patients with progressive unresectable liver metastases from digestive neuroendocrine tumor were treated with TACE (mean of 3.6 sessions) before any non-surgical treatment (somatostatin analogue, chemotherapy or interferon). Liver involvement was less than 50% in 11 patients. Size of the largest lesion ranged from 1.5 to 10 cm. Ten patients presented with carcinoid symptoms. The TACE was performed with Doxorubicin emulsified in Lipiodol and gelatin sponge particles. Symptomatic response upon flushes and/or diarrhea was complete in 7 of 10 cases and partial in 2 of 10 cases. An objective morphologic response was noted in 12 of 14 cases. The 5- and 10-year survival rate from diagnosis was 83 and 56%, respectively. Six patients were alive at the end of the study after 27-100 months from first TACE and 38-142 months from diagnosis. Three of them were successfully palliated for 55, 69, and 100 months with only TACE as treatment. Long-term palliation is possible in unresectable liver metastases from digestive neuroendocrine tumors with a few sessions of TACE as first-line and eventually exclusive treatment. (orig.)

  13. FIRST-LINE TREATMENT IN PATIENTS WITH INOPERABLE METASTATIC COLON CANCER

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    M. Yu. Fedyanin

    2014-01-01

    Full Text Available First-line therapy for metastatic colon cancer is most important for a patient. Its median time to progression constitutes the bulk of the patient’s survival. Clearly, it is necessary to choose the most effective combinations of targeted drugs and chemotherapy regimens. The choice of therapy for patients with colon cancer is governed by both the clinical characteristics of the disease and the molecular changes of a tumor. In recent literature, there has been a great deal of evidence for the use of targeted drugs in different clinical situations; the results of comparative trials of different treatment combinations have been published. This all determines the reconsideration of the choice of a treatment regimen in patients with metastatic colon cancer; it is the topic of the present review.

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

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    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-effectiveness...

  15. 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.

  16. Modification of First-line Antiretroviral Therapy in Treatment-naive, HIV Positive Patients

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    Smita Shenoy

    2017-10-01

    Full Text Available Introduction: Modification of initial Antiretroviral Therapy (ART program is an important issue in HIV infected patients as the number of ART regimens available is limited. Hence, there is a need to understand the factors that affect modification and therefore, the durability of the initial antiretroviral regimen. Aim: To study the type of modification of first line ART in treatment-naive HIV positive patients and factors influencing it. Materials and Methods: A retrospective observational study was carried out in the HIV clinic of a tertiary care hospital, using data obtained from the case records of the subjects who were initiated on ART between January 2012 to December 2014. Data on patient baseline characteristics, proportion of patients who required modification, type and time of modification was collected. The determinants of time to modification were analysed using Chi-square test. Binomial logistic regression was utilized to assess independent risk factors for change in regimen. Results: Out of 200 case records analysed, 54 patients had to undergo a modification in their initial regimen. The mean age of patients was 44.68 ± 11.31 years. Majority of the patients were males. The most common reason for modification was Adverse Drug Reactions (ADRs (79.63% followed by treatment failure (9.25%. In 85.18% cases, modification involved substitution. Occurrence of ADRs and non-tenofovir based first-line regimens were associated with higher likelihood of substitution in regimen (p<0.05. The median time (IQR to modification was 173 (152.25, 293.50 days. Conclusion: ADRs and the use of non-tenofovir based regimens resulted in significantly higher rates of modification of antiretroviral therapy. There should be monitoring of patients on ART to detect ADRs at the earliest and to obtain increased use of single tablet containing tenofovir based regimen to improve durability of first line regimens.

  17. [Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

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    Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

    2017-06-20

    With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

  18. Aspirin is first-line treatment for migraine and episodic tension-type headache regardless of headache intensity.

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    Lampl, Christian; Voelker, Michael; Steiner, Timothy J

    2012-01-01

    (1) To establish whether pre-treatment headache intensity in migraine or episodic tension-type headache (ETTH) predicts success or failure of treatment with aspirin; and (2) to reflect, accordingly, on the place of aspirin in the management of these disorders. Stepped care in migraine management uses symptomatic treatments as first-line, reserving triptans for those in whom this proves ineffective. Stratified care chooses between symptomatic therapy and triptans as first-line on an individual basis according to perceived illness severity. We questioned the 2 assumptions underpinning stratified care in migraine that greater illness severity: (1) reflects greater need; and (2) is a risk factor for failure of symptomatic treatment but not of triptans. With regard to the first assumption, we developed a rhetorical argument that need for treatment is underpinned by expectation of benefit, not by illness severity. To address the second, we reviewed individual patient data from 6 clinical trials of aspirin 1000 mg in migraine (N = 2079; 1165 moderate headache, 914 severe) and one of aspirin 500 and 1000 mg in ETTH (N = 325; 180 moderate, 145 severe), relating outcome to pre-treatment headache intensity. In migraine, for headache relief at 2 hours, a small (4.7%) and non-significant risk difference (RD) in therapeutic gain favored moderate pain; for pain freedom at 2 hours, therapeutic gains were almost identical (RD: -0.2%). In ETTH, for headache relief at 2 hours, RDs for both aspirin 500 mg (-4.2%) and aspirin 1000 mg (-9.7%) favored severe pain, although neither significantly; for pain freedom at 2 hours, RDs (-14.2 and -3.6) again favored severe pain. In neither migraine nor ETTH does pre-treatment headache intensity predict success or failure of aspirin. This is not an arguable basis for stratified care in migraine. In both disorders, aspirin is first-line treatment regardless of headache intensity. © 2011 American Headache Society.

  19. Learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer.

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    Lendínez-Cano, G; Osman García, I; Congregado Ruiz, C B; Conde Sánchez, J M; Medina López, R A

    2018-03-07

    To analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves. The learning curve was analysed with the cumulative sum (CUSUM) methodology. In our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9-17.1). The mean time to progression was 30.4 months (95% CI 22.7-38.1), and the mean overall survival was 34.9 months (95% CI 27.8-42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1-15), phase 2 (16-26) in which the management of the drug progressively improved and phase 3 (27-32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. Despite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Temsirolimus Is Highly Effective as Third-Line Treatment in Chromophobe Renal Cell Cancer

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    Dimitrios Zardavas

    2011-01-01

    Full Text Available We report unexpectedly high efficacy of temsirolimus as third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. After failure of two sequentially administered tyrosine kinase inhibitors, treatment with temsirolimus resulted in a prolonged partial remission of 14 months, and the response is still continuing. Up to now, no data from randomized clinical studies have been published addressing the question of efficacy of temsirolimus as third-line treatment after failure of tyrosine kinase inhibitors. The case presented here implies that temsirolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.

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

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    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

  2. Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

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    Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

    2014-08-01

    A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

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

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    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

  4. First-line treatment disruption among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study.

    Science.gov (United States)

    Tang, Derek H; Li, Nanxin; Du, Ella X; Peeples, Miranda; Chu, Lihao; Xie, Jipan; Barghout, Victoria

    2017-12-01

    This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2- metastatic breast cancer (mBC) in the US. Post-menopausal women with HR+/HER2- mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1-42.2%), liver (8.8-17.3%), and lung (8.6-9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2- mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.

  5. Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

    Science.gov (United States)

    Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

    2014-07-01

    In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

  6. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma

    Science.gov (United States)

    Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L.

    2018-01-01

    Importance Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti–programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). Objective To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. Design, Setting, and Participants JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Interventions Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Main Outcomes and Measures Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. Results As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing

  7. 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.

  8. 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...

  9. 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

  10. Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

    Science.gov (United States)

    Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

    2016-01-01

    Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for

  11. Pharmacoeconomic analysis of the use of first- and second-line drugs in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    V. R. Mkrtchyan

    2015-01-01

    Full Text Available Objective: to make a pharmacoeconomic comparison of the administration of first- and second-line drugs in the treatment of multiple sclerosis through cost, cost-effectiveness, and budget impact analyses using the 2015 state prices.Material and methods. A pharmacoeconomic analysis was carried out on the basis of the data available in the literature on trials of the effects of the drugs on the rates of exacerbations and disability. On calculating, the authors took into account the current standards for the out- and inpatient management of patients with this nosological entity in accordance with the compulsory health insurance (CHI program; prices for state drug purchases in March 2015; prices for medical services in compliance with the CHI standards in Moscow in 2015; the average sizes of minimum wage, salary, and disability grants with consideration for a discount rate of 3%. The cost-effectiveness and budget impact analyses were performed for intramuscular interferon (INF-β1a (avonex, 30 μg, subcutaneous INF-β1a (rebif, 44 μg, subcutaneous INF-β1b (ronbetal, 8,000,000 IU, subcutaneous INF-β1b (betaferon, 9,600,000 IU, subcutaneous glatiramer acetate (copaxone, 20 mg, intravenous natalizumab (tyzabri, 300 mg, and oral fingolimod (gilenya, 0.5 mg.Results and discussion. The second-line drug tyzabri outperforms the first-line agents for cost-effectiveness. The first-line drugs betaferon and copaxone is slightly exceeded in this indicator by tyzabri; the other both first- and second-line agents compared are all the more inferior in this indicator. The budget impact analysis has shown that the cost of the second-line drugs was higher than that of the first-line ones.

  12. First-line antiretroviral drug discontinuations in children.

    Directory of Open Access Journals (Sweden)

    Melony Fortuin-de Smidt

    Full Text Available 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.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.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.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 Organization recommendation to replace stavudine with

  13. Efficacy and safety of combinations of first-line topical treatments in chronic plaque psoriasis: a systematic literature review

    NARCIS (Netherlands)

    Hendriks, A.G.M.; Keijsers, R.R.M.C.; Jong, E.M.G.J. de; Seyger, M.M.B.; Kerkhof, P.C.M. van de

    2013-01-01

    Background Most psoriasis patients suffering from mild to moderate disease are treated with first-line topical treatments, including corticosteroids, vitamin D analogues, topical retinoids and calcineurin inhibitors. Although evidence-based guidelines on combinations are lacking, the majority of

  14. IVF or IUI as first-line treatment in unexplained subfertility: the conundrum of treatment selection markers.

    Science.gov (United States)

    Tjon-Kon-Fat, R I; Tajik, P; Zafarmand, M H; Bensdorp, A J; Bossuyt, P M M; Oosterhuis, G J E; van Golde, R; Repping, S; Lambers, M D A; Slappendel, E; Perquin, D; Pelinck, M J; Gianotten, J; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W; van Wely, M

    2017-05-01

    Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). Since this is the first large study that looked at

  15. Regorafenib plus modified FOLFOX6 as first-line treatment of metastatic colorectal cancer: A phase II trial.

    Science.gov (United States)

    Argilés, Guillem; Saunders, Mark P; Rivera, Fernando; Sobrero, Alberto; Benson, Al; Guillén Ponce, Carmen; Cascinu, Stefano; Van Cutsem, Eric; Macpherson, Iain R; Strumberg, Dirk; Köhne, Claus-Henning; Zalcberg, John; Wagner, Andrea; Luigi Garosi, Vittorio; Grunert, Julia; Tabernero, Josep; Ciardiello, Fortunato

    2015-05-01

    The oral multikinase inhibitor regorafenib improves overall survival (OS) in patients with metastatic colorectal cancer (CRC) for which all standard treatments have failed. This study investigated regorafenib plus modified FOLFOX (mFOLFOX6) as first-line treatment of metastatic CRC. In this single-arm, open-label, multicentre, phase II study, patients received mFOLFOX6 on days 1 and 15, and regorafenib 160 mg orally once daily on days 4-10 and 18-24 of each 28-day cycle. The primary end-point was centrally assessed objective response rate (ORR). Secondary end-points included disease control rate (DCR), OS, progression-free survival (PFS) and safety. Median overall treatment duration with any study drug was 9.9 months (range 0.6-19.6); median treatment duration with regorafenib was 7.7 months (range 0.1-19.5); six patients remained on regorafenib for more than 1 year. Fifty-three patients received at least one dose of regorafenib. ORR was 43.9% (all partial responses); DCR was 85.4%; median OS was not reached; median PFS was 8.5months. Treatment-emergent adverse events were experienced by all patients but were manageable with dose modifications. Regorafenib+mFOLFOX6 as first-line treatment in patients with metastatic CRC did not improve ORR over historical controls. Regorafenib plus mFOLFOX6 did not appear to be associated with a markedly worse tolerability profile versus mFOLFOX6 alone. Copyright © 2015. Published by Elsevier Ltd.

  16. Qualitative study of patients’ decision-making when accepting second-line treatment after failure of first-line chemotherapy

    Science.gov (United States)

    Roch, Benoît; Roth, Caroline; Mérel, Jean-Pierre

    2018-01-01

    Objective Treatment failures in advanced lung cancer are frequent events affecting patients during or after first-line chemotherapy. International guidelines recommend second-line chemotherapy. However, around one half of patients who experience disease progression enter a systemic second-line therapy. In the herein qualitative study, we investigated patients' thoughts and attitudes determining the decision to undergo a second-line chemotherapy. Methods Thirty-three purposively selected patients who recently accepted second-line or palliative chemotherapy were invited to participate in this survey consisting of semi-structured in-depth interviews. Grounded theory was applied to investigate participants’ perceptions of the context that have surrounded their decision to undergo palliative chemotherapy. Results For most patients, tumor burden and reduced quality of life in relation with lung cancer itself were major drivers of the decision-making process. There was a balance between two different attitudes: making a decision to undergo a new line of chemotherapy or starting a psychological process in order to accept end of life. Choosing between these two attitudes allowed the patient to keep the matter of palliative care at a distance. Even in case of low chance of success, many patients who worried about their life partner's future would accept a new chemotherapy line. Some patients experienced ambivalent thoughts regarding social network, particularly about their family as daily function impairment required an increased need for relative's support. The initial "Worrying about others" thoughts left place to in an increasing self-need of care as those provided by relatives; this phenomenon might increase patients' self- perception of being a burden for others. Confidence previously established with formal caregiver support was another major decision driver: some patients with sustained confidence in their medical staff may have privileged this formal support rather

  17. 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

    : The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first-line therapy, although the patients who received belinostat had a higher investigator-assessed response rate. Future trials in CUP should focus on specific subsets, defined either......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......, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients...

  18. First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012.

    Science.gov (United States)

    Bacigalupo, Andrea; Oneto, Rosi; Schrezenmeier, Hubert; Hochsmann, Britta; Dufour, Carlo; Kojima, Seiji; Zhu, Xiaofan; Chen, Xiaojuan; Issaragrisil, Surapol; Chuncharunee, Suporn; Jeong, Dae Chul; Giammarco, Sabrina; Van Lint, Maria Teresa; Zheng, Yizhou; Vallejo, Carlos

    2018-05-01

    The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival. © 2018 Wiley Periodicals, Inc.

  19. Non small-cell lung cancer and treatment options after tyrosine kinase inhibitors failure in the first line

    International Nuclear Information System (INIS)

    Chowaniecova, G.

    2014-01-01

    Introduction: Advanced non-small cell lung cancer with present epidermal growth factor receptor (EGFR) sensitising mutation is standardly treated with tyrosine kinase inhibitors (TKI). During treatment a resistance to TKI develops, disease progresses. We differ primary and secondary resistance. The most effective treatment after TKI failure is not definitively proven. Standard chemotherapy is usually introduced, eventually it is possible to use other TKI in the next lines. Case: The author presents a case of 60-year old patient with lung adenocarcinoma with EGFR sensitising mutation, where primary resistance to TKI was observed. Chemotherapy after progression was introduced. Planned therapy with afatnib was not carried out due to deterioration of patient´s condition. Conclusion: Presented case of EGFR mutation-positive patient represents an example of not very frequent primary resistance to TKI. Mechanisms of primary resistance are not well understood. Treatment after first line TKI failure in non-small cell lung cancer with EGFR mutation represents a challenge for medical research. (author)

  20. Genetic variants as ovarian cancer first-line treatment hallmarks: A systematic review and meta-analysis.

    Science.gov (United States)

    Assis, Joana; Pereira, Carina; Nogueira, Augusto; Pereira, Deolinda; Carreira, Rafael; Medeiros, Rui

    2017-12-01

    The potential predictive value of genetic polymorphisms in ovarian cancer first-line treatment is inconsistently reported. We aimed to review ovarian cancer pharmacogenetic studies to update and summarize the available data and to provide directions for further research. A systematic review followed by a meta-analysis was conducted on cohort studies assessing the involvement of genetic polymorphisms in ovarian cancer first-line treatment response retrieved through a MEDLINE database search by November 2016. Studies were pooled and summary estimates and 95% confidence intervals (CI) were calculated using random or fixed-effects models as appropriate. One hundred and forty-two studies gathering 106871 patients were included. Combined data suggested that GSTM1-null genotype patients have a lower risk of death compared to GSTM1-wt carriers, specifically in advanced stages (hazard ratio (HR), 0.68; 95% CI, 0.48-0.97) and when submitted to platinum-based chemotherapy (aHR, 0.61; 95% CI, 0.39-0.94). ERCC1 rs11615 and rs3212886 might have also a significant impact in treatment outcome (aHR, 0.67; 95% CI, 0.51-0.89; aHR, 1.28; 95% CI, 1.01-1.63, respectively). Moreover, ERCC2 rs13181 and rs1799793 showed a distinct ethnic behavior (Asians: aHR, 1.41; 95% CI, 0.80-2.49; aHR, 1.07; 95% CI, 0.62-1.86; Caucasians: aHR, 0.10; 95% CI, 0.01-0.96; aHR, 0.18; 95% CI, 0.05-0.68, respectively). The definition of integrative predictive models should encompass genetic information, especially regarding GSTM1 homozygous deletion. Justifying additional pharmacogenetic investigation are variants in ERCC1 and ERCC2, which highlight the DNA Repair ability to ovarian cancer prognosis. Further knowledge could aid to understand platinum-treatment failure and to tailor chemotherapy strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Introduction of dermatome shaving as first line treatment of chronic tattoo reactions.

    Science.gov (United States)

    Sepehri, Mitra; Jørgensen, Bo; Serup, Jørgen

    2015-10-01

    Chronic tattoo reactions requiring treatment have increased. Laser removal is not ideal for removal of allergic reactions. Surgical removal of culprit pigment situated in the outer dermis by dermatome shaving is rational and need to be revisited. Fifty four tattoos with chronic reactions in 50 patients were treated with dermatome shaving. Tattoos with red/red nuances dominated the material. In total, 52 operations were performed in infiltration and 2 in general anaesthesia. Shaving was performed to the level in the dermis free of tattoo pigment as assessed visually by the surgeon. Operative complications were few. Healing occurred over weeks as normal for this procedure. On a rating scale from 0 to 4, 4 as most severe, the patient's severity rating of symptoms in their tattoo declined from 3.2 pre-operatively to 1.0, 0.8 and 0.7 after 3, 6 and 12 months, respectively. Burden of operation was rated low. Patient satisfaction was high. Dermatome shaving is efficient and with few complications, and is proposed as first line treatment of chronic tattoo reactions. Shaving of such reactions apparently has been neglected during enthusiastic introduction of laser approaches, which in the treatment of allergic tattoo reactions may be relatively contra indicated and of special risk.

  2. “…still waiting for chloroquine”: the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district

    Science.gov (United States)

    2014-01-01

    Background Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. Objectives To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Methods Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Results Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing

  3. Immunotherapy “Shock” a case series of PD-L1 100% and pembrolizumab first-line treatment

    Directory of Open Access Journals (Sweden)

    Paul Zarogoulidis

    2017-01-01

    Full Text Available In this decade a “bloom” of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

  4. Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile-Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic Evaluation.

    Science.gov (United States)

    Reveles, Kelly R; Backo, Jennifer L; Corvino, Frank A; Zivkovic, Marko; Broderick, Kelly C

    2017-12-01

    The reduction in recurrent Clostridium difficile-associated diarrhea (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to lower overall CDAD costs. However, studies assessing the cost-effectiveness of fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking. This study evaluated the costs associated with utilizing fidaxomicin or vancomycin as a first-line therapy for CDAD in specific patient populations from a U.S. hospital perspective. A decision-analytic model was developed to estimate total costs (hospitalization and drug costs) associated with using fidaxomicin or vancomycin as first-line therapy for a first episode and up to two recurrences of CDAD in five patient populations: general population, elderly, patients receiving concomitant antibiotics, and patients with renal impairment or cancer. The total cost of CDAD treatment using fidaxomicin first line in the general population was $14,442 per patient versus $14,179 per patient with vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total hospital cost savings of $616 per patient in patients with cancer and $312 in patients with concomitant antibiotic use; vancomycin use was associated with total hospital cost savings of $243 per patient in the elderly and $371 in patients with renal impairment. Fidaxomicin as first-line CDAD therapy is associated with similar total costs as compounded vancomycin oral solution in the general population. In elderly and renally impaired patients, slight increases in hospital cost were observed with fidaxomicin therapy, and in patients with cancer or concomitant antibiotic use, hospital cost savings were observed. © 2017 Pharmacotherapy Publications, Inc.

  5. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

    DEFF Research Database (Denmark)

    Joensuu, H; Holli, K; Heikkinen, M

    1998-01-01

    PURPOSE: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS: Patients in the single-agent arm...... (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...... younger than 50. RESULTS: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity...

  6. Quantification of viable bacteria in wastewater treatment plants by using propidium monoazide combined with quantitative PCR (PMA-qPCR).

    Science.gov (United States)

    Li, Dan; Tong, Tiezheng; Zeng, Siyu; Lin, Yiwen; Wu, Shuxu; He, Miao

    2014-02-01

    The detection of viable bacteria in wastewater treatment plants (WWTPs) is very important for public health, as WWTPs are a medium with a high potential for waterborne disease transmission. The aim of this study was to use propidium monoazide (PMA) combined with the quantitative polymerase chain reaction (PMA-qPCR) to selectively detect and quantify viable bacteria cells in full-scale WWTPs in China. PMA was added to the concentrated WWTP samples at a final concentration of 100 micromol/L and the samples were incubated in the dark for 5 min, and then lighted for 4 min prior to DNA extraction and qPCR with specific primers for Escherichia coli and Enterococci, respectively. The results showed that PMA treatment removed more than 99% of DNA from non-viable cells in all the WWTP samples, while matrices in sludge samples markedly reduced the effectiveness of PMA treatment. Compared to qPCR, PMA-qPCR results were similar and highly linearly correlated to those obtained by culture assay, indicating that DNA from non-viable cells present in WWTP samples can be eliminated by PMA treatment, and that PMA-qPCR is a reliable method for detection of viable bacteria in environmental samples. This study demonstrated that PMA-qPCR is a rapid and selective detection method for viable bacteria in WWTP samples, and that WWTPs have an obvious function in removing both viable and non-viable bacteria. The results proved that PMA-qPCR is a promising detection method that has a high potential for application as a complementary method to the standard culture-based method in the future.

  7. New developments in cognitive behavioral therapy as the first-line treatment of insomnia

    Directory of Open Access Journals (Sweden)

    Allison T Siebern

    2011-02-01

    Full Text Available Allison T Siebern, Rachel ManberSleep Medicine Center, Stanford University School of Medicine, Redwood City, California, USAAbstract: Insomnia is the most common sleep disorder. Psychological, behavioral, and biological factors are implicated in the development and maintenance of insomnia as a disorder, although the etiology of insomnia remains under investigation, as it is still not fully understood. Cognitive behavioral therapy for insomnia (CBTI is a treatment for insomnia that is grounded in the science of behavior change, psychological theories, and the science of sleep. There is strong empirical evidence that CBTI is effective. Recognition of CBTI as the first-line treatment for chronic insomnia (National Institutes of Health consensus, British Medical Association was based largely on evidence of its efficacy in primary insomnia. The aim of this article is to provide background information and review recent developments in CBTI, focusing on three domains: promising data on the use of CBTI when insomnia is experienced in the presence of comorbid conditions, new data on the use of CBTI as maintenance therapy, and emerging data on the delivery of CBTI through the use of technology and in primary care settings.Keywords: insomnia, CBTI, nonpharmacological treatment

  8. Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

    Science.gov (United States)

    Birolo, Carolina; Zannin, Maria Elisabetta; Arsenyeva, Svetlana; Cimaz, Rolando; Miserocchi, Elisabetta; Dubko, Margarita; Deslandre, Chantal Job; Falcini, Fernanda; Alessio, Maria; La Torre, Francesco; Denisova, Ekaterina; Martini, Giorgia; Nikishina, Irina; Zulian, Francesco

    2016-11-01

    Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis. In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded. Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile. ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

  9. Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

    Science.gov (United States)

    Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

    2014-09-01

    For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

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

    Directory of Open Access Journals (Sweden)

    Viktor von Wyl

    Full Text Available BACKGROUND: 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 their impact on second-line therapy. METHODS: We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base and pessimistic (extensive emergence assumptions regarding occurrence of multidrug resistance patterns were tested. RESULTS: In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%] compared with first-line TDF users (31% [29%; 33%]. Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]. At the time of second-line initiation, a higher proportion (16% of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively. In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315

  11. Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients.

    Science.gov (United States)

    Puz, Przemysław; Lasek-Bal, Anetta

    2016-11-10

    BACKGROUND In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year. MATERIAL AND METHODS Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed. RESULTS The annualized relapse rate for second-line therapy was significantly lower than for first-line therapy (0.35±0.74 vs. 2.13±0.87, p=0.00005). Median of EDSS progression with first-line therapy was significantly higher than that with natalizumab or fingolimod treatment (p=0.00002). The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year second-line treatment was significantly lower in comparison to lesions in MRI performed at the end of the first-line therapy (for T2: 0.61 vs. 4.56, p=0.0004; for Gd+: 0.13 vs. 1.98, p=0.0009). No significant differences in the clinical data, MRI results, and side effects between fingolimod and natalizumab patients have been observed. CONCLUSIONS Treatment with natalizumab or fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.

  12. The use of anthracycline at first-line compared to alkylating agents or nucleoside analogs improves the outcome of salvage treatments after relapse in follicular lymphoma The REFOLL study by the Fondazione Italiana Linfomi.

    Science.gov (United States)

    Rossi, Giuseppe; Marcheselli, Luigi; Dondi, Alessandra; Bottelli, Chiara; Tucci, Alessandra; Luminari, Stefano; Arcaini, Luca; Merli, Michele; Pulsoni, Alessandro; Boccomini, Carola; Puccini, Benedetta; Micheletti, Moira; Martinelli, Giovanni; Rossi, Andrea; Zilioli, Vittorio Ruggero; Bozzoli, Valentina; Balzarotti, Monica; Bolis, Silvia; Cabras, Maria Giuseppina; Federico, Massimo

    2015-01-01

    Follicular lymphoma (FL) patients experience multiple remissions and relapses and commonly receive multiple treatment lines. A crucial question is whether anthracyclines should be used at first-line or whether they would be better "reserved" for relapse and whether FL outcome can be optimized by definite sequences of treatments. Randomized trials can be hardly designed to address this question. In this retrospective multi-institutional study, time-to-next-treatment after first relapse was analyzed in 510 patients who had received either alkylating agents- or anthracycline- or nucleoside analogs-based chemotherapy with/without rituximab at first-line and different second-line therapies. After a median of 42 months, median time-to-next-treatment after relapse was 41 months (CI95%:34-47 months). After adjustment for covariates, first-line anthracycline-based chemotherapy with/without rituximab was associated with better time-to-next-treatment after any salvage than alkylating agents-based chemotherapy with/without rituximab or nucleoside analogs-based chemotherapy with/without rituximab (HR:0.74, P = 0.027). The addition of rituximab to first-line chemotherapy had no significant impact (HR:1.22, P = 0.140). Autologs stem cell transplantation performed better than any other salvage treatment (HR:0.53, P < 0.001). First-line anthracycline-based chemotherapy significantly improved time-to-next-treatment even in patients receiving salvage autologs stem cell transplantation (P = 0.041). This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line. © 2014 Wiley Periodicals, Inc.

  13. Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Annette Pflugfelder

    Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

  14. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  15. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.

    Science.gov (United States)

    Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

    2015-09-01

    BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.

  16. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia.

    Science.gov (United States)

    Ayalew, Mohammed Biset; Kumilachew, Dawit; Belay, Assefa; Getu, Samson; Teju, Derso; Endale, Desalegn; Tsegaye, Yemisirach; Wale, Zebiba

    2016-01-01

    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. 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. Pfailure. 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. 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/mm(3)).

  17. First-line targeted therapies in the treatment of metastatic colorectal cancer – role of cetuximab

    Directory of Open Access Journals (Sweden)

    Giuseppe Tonini

    2009-04-01

    Full Text Available Giuseppe Tonini, Alice Calvieri, Bruno Vincenzi, Daniele SantiniMedical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Worldwide, colorectal cancer (CRC is the fourth most commonly diagnosed malignant disease and the second leading cause of cancer-related death in Western nations. In 2008 there were an estimated 148,810 new cases and 49,960 deaths in the US. For several years different chemotherapeutic regimens, based on floropyrimidines, irinotecan and oxaliplatin, have been used in advanced CRC, but survival is still unsatisfactory. New targeted therapies, including drugs and monoclonal antibodies (MoABs , show great promise in the fight against CRC and have shown activity in different disease settings. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR, is active in metastatic colorectal cancer (mCRC. As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The combination of this drug with classical chemotherapies has shown better clinical profiles reflected in an improvement in overall and progression-free survival. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. Whereas cetuximab has a clear indication in the salvage setting, its role in first-line therapy remains investigational. It is particularly encouraging that cetuximab may enhance curative opportunities in patients with early metastatic disease, suggesting that adding cetuximab in first-line therapy may downstage disease in some patients, and, as a result, allow potentially curative resection of previously unresectable metastases. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit, and the role of cetuximab in first-line treatment of metastatic CRC

  18. First and second line drug resistance among treatment naïve pulmonary tuberculosis patients in a district under Revised National Tuberculosis Control Programme (RNTCP in New Delhi

    Directory of Open Access Journals (Sweden)

    Vithal Prasad Myneedu

    2015-12-01

    Full Text Available There is limited information of level of drug resistance to first-line and second line anti-tuberculosis agents in treatment naïve pulmonary tuberculosis (PTB patients from the Indian region. Therefore, the present prospective study was conducted to determine the antimicrobial susceptibility to first-line and second line anti-TB drug resistance in such patients. Sputum samples from consecutive treatment naïve PTB cases registered in Lala Ram Sarup (LRS district, under RNTCP containing 12 Directly Observed Treatment Centre’s (DOTS, were enrolled using cluster sampling technology. A total of 453 samples were received from July 2011 to June 2012. All samples were cultured on solid medium followed by drug susceptibility to first and second line anti-tubercular drugs as per RNTCP guidelines. Primary multi-drug resistance (MDR was found to be 18/453; (4.0%. Extensively drug resistance (XDR was found in one strain (0.2%, which was found to be resistant to other antibiotics. Data of drug resistant tuberculosis among treatment naïve TB patients are lacking in India. The presence of XDR-TB and high MDR-TB in small population studied, calls for conducting systematic multi-centric surveillance across the country.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Putative contribution of CD56 positive cells in cetuximab treatment efficacy in first-line metastatic colorectal cancer patients

    International Nuclear Information System (INIS)

    Maréchal, Raphaël; De Schutter, Jef; Nagy, Nathalie; Demetter, Pieter; Lemmers, Arnaud; Devière, Jacques; Salmon, Isabelle; Tejpar, Sabine; Van Laethem, Jean-Luc

    2010-01-01

    Activity of cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor, is largely attributed to its direct antiproliferative and proapoptotic effects. Antibody-dependent cell-mediated cytotoxicity (ADCC) could be another possible mechanism of cetuximab antitumor effects and its specific contribution on the clinical activity of cetuximab is unknown. We assessed immune cells infiltrate (CD56, CD68, CD3, CD4, CD8, Foxp3) in the primary tumor of metastatic colorectal cancer (mCRC) patients treated with a first-line cetuximab-based chemotherapy in the framework of prospective trials (treatment group) and in a matched group of mCRC patients who received the same chemotherapy regimen without cetuximab (control group). The relationship between intra-tumoral immune effector cells, the K-ras status and the efficacy of the treatment were investigated. We also evaluated in vitro, the ADCC activity in healthy donors and chemonaive mCRC patients and the specific contribution of CD56 + cells. ADCC activity against DLD1 CRC cell line is maintained in cancer patients and significantly declined after CD56 + cells depletion. In multivariate analysis, K-ras wild-type (HR: 4.7 (95% CI 1.8-12.3), p = 0.001) and tumor infiltrating CD56 + cells (HR: 2.6, (95%CI:1.14-6.0), p = 0.019) were independent favourable prognostic factors for PFS and response only in the cetuximab treatment group. By contrast CD56 + cells failed to predict PFS and response in the control group. CD56 + cells, mainly NK cells, may be the major effector of ADCC related-cetuximab activity. Assessment of CD56 + cells infiltrate in primary colorectal adenocarcinoma may provide additional information to K-ras status in predicting response and PFS in mCRC patients treated with first-line cetuximab-based chemotherapy

  1. Rituximab as a first-line agent for the treatment of dermatomyositis.

    LENUS (Irish Health Repository)

    2012-02-01

    B cells may play a pivotal role in the pathophysiology of DM, and reports have claimed that targeting B cells is a viable treatment option in patients with dermatomyositis. A 20-year-old girl presented in October 2007, with few weeks\\' history of proximal muscle weakness. Gottron\\'s papules were noted on her knuckles. She had normal inflammatory markers and negative autoantibody screen. Her CPK was 7,000 U\\/L (normal range 0-170) with an LDH of 1,300 U\\/L (normal range 266-500). EMG and muscle biopsy was consistent with active myositis. She had normal pulmonary function tests. HRCT showed no interstitial lung disease. She was started with 60 mg glucocorticoids (1 mg\\/kg), with a good clinical response. However, any attempt to taper down the steroid dose led to recurrence of her symptoms. The options of available immunosuppressive therapies, including the experimental usage of rituximab, were discussed with her; averse to long-term systemic treatments, she opted to try a course of rituximab. She had rituximab 1,000 mg on days 0 and 14, and her glucocorticoids were tapered in next few weeks. Now, 24 months since her rituximab infusions, she remains in complete clinical and biochemical remission and is naive to other immunosuppressive agents apart from glucocorticoids and rituximab. Depleting peripheral B cells with rituximab (one course) in our patient has led not only to complete resolution of muscle and skin disease (induction) but also remains off all immunosuppressives including glucocorticoids.

  2. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer.

    Science.gov (United States)

    Vogel, Charles L; Cobleigh, Melody A; Tripathy, Debu; Gutheil, John C; Harris, Lyndsay N; Fehrenbacher, Louis; Slamon, Dennis J; Murphy, Maureen; Novotny, William F; Burchmore, Michael; Shak, Steven; Stewart, Stanford J; Press, Michael

    2002-02-01

    To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Improvement in dose escalation using off-line and on-line image feedback in the intensity modulated beam design for prostate cancer treatment

    International Nuclear Information System (INIS)

    Yan, D.; Birkner, M.; Nuesslin, F.; Wong, J.; Martinez, A.

    2001-01-01

    Purpose: To test the capability of dose escalation in the IMRT process where the organ/patient temporal geometric variation, measured using either off-line or on-line treatment CT and portal images, are adapted for the optimal design of intensity modulated beam. Materials and Methods: Retrospective study was performed on five prostate cancer patients with multiple CT scans (14∼17/patient) and daily portal images obtained during the treatment course. These images were used to determine the displacements of each subvolume in the organs of interest caused by the daily patient setup and internal organ motion/deformation. The temporal geometric information was processed in order of treatment time and fed into an inverse planning system. The inverse planning engine was specifically implemented to adapt the design of intensity modulated beam to the temporal subvolume displacement and patient internal density changes. Three image feedback strategies were applied to each patient and evaluated with respect to the capability of safe dose escalation. The first one is off-line image feedback, which designs the beam intensity based on the patient images measured within the first week of treatment. The second is an on-line 'the target of the day' strategy, which designs the beam intensity in daily bases by using 'the image of the day' alone. The last one is also the on-line based. However, it designs the instantaneous beam intensity based on also dose distribution in each organ of interest received prior to the current treatment. For each of the treatment strategies, the minimum dose delivered to the CTV was determined by applying the identical normal tissue constraints of partial dose/volumes. This minimum dose was used to represent the treatment dose for each patient. Results: The off-line strategy appears feasible after 5 days of image feedback. The average treatment dose among the patients can be 10% higher than the one in the conventional IMRT treatment where the inverse

  5. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

    Directory of Open Access Journals (Sweden)

    Johann von Felden

    2016-11-01

    Full Text Available Advanced hepatocellular carcinoma (HCC with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST is helpful to identify patients who do not benefit from sorafenib treatment.

  6. Delays in switching patients onto second-line antiretroviral treatment ...

    African Journals Online (AJOL)

    Background: South Africa has one of the largest antiretroviral treatment (ART) programmes globally. In addition to increasing access to ART, it is important that the health system also focuses on the appropriate management of patients who fail first-line ART. Delays in switching patients onto second-line ART can adversely ...

  7. Balancing risk and benefit for first-line treatment of metastatic colorectal cancer: a graphic communication tool for patients and physicians.

    Science.gov (United States)

    Sanatani, Michael S; Vincent, Mark D

    2007-01-01

    Advances in the treatment of metastatic colorectal cancer have improved overall survival (OS); however, this might come at the cost of increased toxicity. Health-related quality of life, a significant concern closely related to toxicity and important when discussing palliative therapy, is infrequently assessed and reported in older clinical trials. As the number of tested regimens increases, the question arises on how to best present palliative treatment options. We present a simple way to compare treatment options in terms of potential risks and benefits. The literature was surveyed for reports of first-line systemic chemotherapies for metastatic colorectal cancer. The largest recent reports with detailed toxicity data were selected as representative for a regimen. Toxicity sum of a regimen was calculated as percent occurrences in the study cohort of severe adverse effects: diarrhea, mucositis, neurocutaneous conditions (excluding alopecia), vomiting, and febrile neutropenia. Limitations of toxicity reporting precluded inclusion of other or milder adverse events. Benefits (OS and progression-free survival [PFS]) were plotted graphically as benefit versus toxicity sum. Thirty-four regimens were found. Overall survival, PFS, and toxicity sum ranged from 8.9-24.7 months, 4.9-9.2 months, and 12-70 months, respectively. Weaknesses of our study include omission of some specific toxicities and of symptom control benefit, as well as heterogeneity of trial design and study populations. Furthermore, more recent OS data might reflect the availability of more lines of therapy rather than the effect of the first-line regimen, as comparison with PFS outcomes show. Our comparative tool helps physicians discuss the large number of available options with a patient in order to arrive at the treatment plan most appropriate to the individual and improve informed consent and disclosure, while highlighting limitations in available evidence.

  8. Metastatic melanoma: results of 'classical' second-line treatment with cytotoxic chemotherapies.

    Science.gov (United States)

    Perrin, Christophe; Pracht, Marc; Talour, Karen; Adamski, Henri; Cumin, Isabelle; Porneuf, Marc; Talarmin, Marie; Mesbah, Habiba; Audrain, Odile; Moignet, Aline; Lefeuvre-Plesse, Claudia; Lesimple, Thierry

    2014-10-01

    Metastatic melanoma is one of the most aggressive tumours, with a median survival that does not exceed 12 months. None of the cytotoxic first-line therapies have shown survival benefit in randomised clinical trials. To describe clinical benefit of second-line cytotoxic chemotherapy in the second line of treatment for metastatic melanoma. In a retrospective study, we analyse the outcome of patients with metastatic melanoma who had received two lines or more of cytotoxic treatments in four French dermato-oncology departments between 1999 and 2009. We describe the outcomes for 109 patients. Most of these patients received dacarbazine for the first line of chemotherapy and fotemustine for the second line of chemotherapy (67.0 and 64.2%, respectively). A clinical benefit was observed in 24.1% of the patients and overall survival was 4.1 months after the second-line treatment. At least 23.8% of patients suffered from grade 3 or 4 toxicities. The presence of more than two sites of metastasis and an M1c staging according to the AJCC classification represented negative predictive factors of clinical benefit. This study shows the modest benefit of a second line of cytotoxic chemotherapy in a nonselected population. If eligible, these patients should be proposed for ongoing clinical trials or for targeted therapies.

  9. 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

  10. 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

  11. 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

  12. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial.

    Science.gov (United States)

    D'Angelo, Sandra P; Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L

    2018-03-22

    Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti-programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing at the time of analysis. In responding patients, the estimated proportion with duration of response of at

  13. Capecitabine and oxaliplatin as second-line treatment in patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Møller, Anne Kirstine Hundahl; Pedersen, Karen Damgaard; Abildgaard, Julie Rafn

    2010-01-01

    tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine.......Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract...

  14. The influence of patient beliefs and treatment satisfaction on the discontinuation of current first-line antiretroviral regimens.

    Science.gov (United States)

    Casado, J L; Marín, A; Romero, V; Bañón, S; Moreno, A; Perez-Elías, M J; Moreno, S; Rodriguez-Sagrado, M A

    2016-01-01

    Large cohort studies have shown a high rate of first-line combination antiretroviral therapy (cART) regimen discontinuation in HIV-infected patients, attributed to characteristics of the cART regimen or toxicity. A cohort study of 274 patients receiving a first-line regimen was carried out. Patients' perceptions and beliefs prior to initiation were assessed using an attitude towards medication scale (0-15 points), and their satisfaction during therapy was assessed using an HIV treatment satisfaction questionnaire (HIVTSQ). Treatment discontinuation was defined as any switch in the cART regimen. During 474.8 person-years of follow-up, 63 (23%) patients changed their cART regimen, mainly because of toxicity/intolerance (42; 67%). The overall rate of change was 13.2 per 100 patient-years [95% confidence interval (CI) 11.1-16.4 per 100 patient-years]. An efavirenz (EFV)-based single tablet regimen showed the highest rate of adverse events (27%), but the lowest rate of change (16%; 7.44 per 100 patient-years). Cox regression revealed a decreased hazard of first regimen termination with better initial attitude towards drugs [hazard ratio (HR) 0.76; 95% CI 0.62-0.93; P satisfaction (HR 0.94; 95% CI 0.89-0.99; P = 0.01), and an increased hazard of termination with the presence of adverse events (HR 7.7; 95% CI 2.4-11.6; P patients (18 of 59; 31%) with mild/moderate adverse events (which were mainly central nervous system symptoms) continued the regimen; these patients, compared with those discontinuing therapy, showed better perception of therapy (mean score 14.4 versus 12.1, respectively; P = 0.05) and greater satisfaction during therapy (mean score 50.6 versus 44.6, respectively; P = 0.04). Patients' beliefs and satisfaction with therapy influence the durability of the first antiretroviral regimen. These patient-related factors modulate the impact of mild adverse events, and could explain differences in the rate of discontinuation. © 2015 British HIV

  15. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  16. 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

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

    OpenAIRE

    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 failu...

  18. First-line HIV treatment: evaluation of backbone choice and its budget impact

    Directory of Open Access Journals (Sweden)

    Orietta Zaniolo

    2013-06-01

    Full Text Available OBJECTIVE: The gradual increase of persons living with HIV, mainly due to the reduced mortality achieved with effective antiretroviral therapies, calls for increased rationality and awareness in health resources consumption also during the early illness phases. Aim of this work is the estimation of the budget impact related to the variation in backbone prescribing trends in naïve patients.METHODS: Target population is the number of patients starting antiretroviral therapy each year, according to the Italian HIV surveillance registry, excluding patients receiving non-authorized or non-recommended regimens. We modeled 3-year mortality and durability rates on a dynamic cohort, basing on international literature. A prevalent patients analysis has also been conducted, for which the model is fed by a closed cohort consisting of all the patients without experience of virologic failure. The aim of this collateral analysis is to estimate the difference in current annual expenditures if the past prescription trends for patients starting therapy would have led to the evaluated hypothetical scenarios. Current Italian market shares of triple regimens containing first-choice or alternative backbones (tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine are compared to three hypothetical scenarios (base-case, minimum and maximum in which increasing shares of patients eligible to abacavir/lamivudine start first line treatment with this backbone. Annual cost for each regimen comprises drugs acquisition under hospital pricing rules, monitoring exams and preventive tests, valued basing on regional reimbursement tariffs.RESULTS: According to current prescribing trends, in the next three years about 13,000 patients starting HIV therapy will receive tenofovir/emtricitabine (83% of the target population, and minor portions other regimens (9% abacavir/lamivudine, 8% zidovudine/lamivudine. Patients that would be eligible to

  19. 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...... Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here...... haplotype (CIRNI) remained high and only changed marginally from 46% to 53% (P = 0.405) after one year with SP as first-line treatment in the study area. Conversely, the combined Pfdhfr/Pfdhps quintuple mutant haplotype increased from 8% to 26% (P = 0.005). The frequency of the chloroquine resistance...

  20. The effectiveness of RECIST on survival in patients with NSCLC receiving chemotherapy with or without target agents as first-line treatment.

    Science.gov (United States)

    Zhou, Ting; Zheng, Lie; Hu, Zhihuang; Zhang, Yang; Fang, Wenfeng; Zhao, Yuanyuan; Ge, Jieying; Zhao, Hongyun; Zhang, Li

    2015-01-08

    We analyzed the correlation between survival and antitumor effect evaluated by RECIST in advanced NSCLC patients with chemotherapy plus target therapy or not as first-line treatment, to examine the applicability of RECIST in this population. The patients were screened from 4 clinical trials (12621, 12006, FASTACT-I, and FASTACT-II), and those who received chemotherapy plus target therapy or chemotherapy alone were eligible. Among the 59 enrolled patients, 29 received combination therapy, while the other 30 received chemotherapy only. In the combination therapy group, patients with PR or SD had longer overall survival (OS) than those with PD (P chemotherapy alone group, compared with PD patients, either PR or SD group had no significant overall survival benefit (P = 0.690 and P = 0.528, respectively). In summary, for advanced NSCLC patients receiving chemotherapy plus target therapy as first-line treatment and evaluated by RECIST criteria, SD has the same overall survival benefit as PR, suggesting that antitumor effective evaluation by RECIST criteria cannot be translated to overall survival benefit especially for this kind of patients. Therefore, developing a more comprehensive evaluation method to perfect RECIST criteria is thus warranted for patients received target therapy in NSCLC.

  1. Uterine Artery Embolization for Retained Products of Conception with Marked Vascularity: A Safe and Efficient First-Line Treatment

    International Nuclear Information System (INIS)

    Bazeries, Paul; Paisant-Thouveny, Francine; Yahya, Sultan; Bouvier, Antoine; Nedelcu, Cosmina; Boussion, Francoise; Sentilhes, Loic; Willoteaux, Serge; Aubé, Christophe

    2017-01-01

    ObjectiveTo report our clinical practice regarding a case series of retained products of conception (RPOC) with marked vascularity (MV) managed with selective uterine artery embolization (UAE) as first-line treatment.MethodsThis was a monocentric, retrospective study of 31 consecutive cases of RPOC with MV diagnosed by Doppler ultrasound in the context of postpartum/postabortal bleeding. The primary outcome was the absence of rebleeding following embolization.ResultsRPOC with MV occurred after abortion in 27 out of 31 patients (87%). The time elapsed between delivery/abortion and UAE ranged from 1 to 210 days (mean 55.7 ± 45 days). Primary clinical success was achieved in 23 women (74.2%) following a single embolization. In total, 27 out of 31 women (87%) had been exclusively managed by UAE with conservative success. Although procedural success was achieved in this number, six women had a further procedure to evacuate RPOC despite procedural success. Large uterine arteriovenous (AV) shunts associated with RPOC were observed in five cases (16.1%), among which two were successfully treated after a single UAE and one after two UAEs, while hysterectomy was performed in the last two cases despite two and three UAE procedures respectively. RPOC was histologically proven in ten cases (32.2%) including four out of five cases of uterine AV shunt.ConclusionRPOC with MV can present with large uterine AV shunt, particularly in case of late management. Uterine artery embolization is an effective and safe first-line treatment, and should be evaluated for this indication in larger prospective trials.

  2. Uterine Artery Embolization for Retained Products of Conception with Marked Vascularity: A Safe and Efficient First-Line Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bazeries, Paul, E-mail: paul.bazeries@chu-angers.fr; Paisant-Thouveny, Francine; Yahya, Sultan; Bouvier, Antoine; Nedelcu, Cosmina [Centre Hospitalier Universitaire d’Angers, Département d’Imagerie Diagnostique et interventionnelle (France); Boussion, Francoise; Sentilhes, Loic [Centre Hospitalier Universitaire d’Angers, Département de Gynécologie et Obstétrique (France); Willoteaux, Serge; Aubé, Christophe [Centre Hospitalier Universitaire d’Angers, Département d’Imagerie Diagnostique et interventionnelle (France)

    2017-04-15

    ObjectiveTo report our clinical practice regarding a case series of retained products of conception (RPOC) with marked vascularity (MV) managed with selective uterine artery embolization (UAE) as first-line treatment.MethodsThis was a monocentric, retrospective study of 31 consecutive cases of RPOC with MV diagnosed by Doppler ultrasound in the context of postpartum/postabortal bleeding. The primary outcome was the absence of rebleeding following embolization.ResultsRPOC with MV occurred after abortion in 27 out of 31 patients (87%). The time elapsed between delivery/abortion and UAE ranged from 1 to 210 days (mean 55.7 ± 45 days). Primary clinical success was achieved in 23 women (74.2%) following a single embolization. In total, 27 out of 31 women (87%) had been exclusively managed by UAE with conservative success. Although procedural success was achieved in this number, six women had a further procedure to evacuate RPOC despite procedural success. Large uterine arteriovenous (AV) shunts associated with RPOC were observed in five cases (16.1%), among which two were successfully treated after a single UAE and one after two UAEs, while hysterectomy was performed in the last two cases despite two and three UAE procedures respectively. RPOC was histologically proven in ten cases (32.2%) including four out of five cases of uterine AV shunt.ConclusionRPOC with MV can present with large uterine AV shunt, particularly in case of late management. Uterine artery embolization is an effective and safe first-line treatment, and should be evaluated for this indication in larger prospective trials.

  3. Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

    Science.gov (United States)

    Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

    2016-06-01

    Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Vaccines against drugs of abuse: a viable treatment option?

    Science.gov (United States)

    Kantak, Kathleen M

    2003-01-01

    Drug addiction is a chronically relapsing brain disorder. There is an urgent need for new treatment options for this disease because the relapse rate among drug abusers seeking treatment is quite high. During the past decade, many groups have explored the feasibility of using vaccines directed against drugs of abuse as a means of eliminating illicit drug use as well as drug overdose and neurotoxicity. Vaccines work by inducing drug-specific antibodies in the bloodstream that bind to the drug of abuse and prevent its entry into the brain. The majority of work in this area has been conducted with vaccines and antibodies directed against cocaine and nicotine. On the basis of preclinical work, vaccines for cocaine and nicotine are now in clinical trials because they can offer long-term protection with minimal treatment compliance. In addition, vaccines and antibodies for phencyclidine, methamphetamine and heroin abuse are currently under development. An underlying theme in this research is the need for high concentrations of circulating drug-specific antibodies to reduce drug-seeking and drug-taking behaviour when the drug is repeatedly available, especially in high doses. Although vaccines against drugs of abuse may become a viable treatment option, there are several drawbacks that need to be considered. These include: a lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice;a lack of an effect on drug craving that predisposes an addict to relapse; and tremendous individual variability in antibody formation. Forced or coerced vaccination is not likely to work from a scientific perspective, and also carries serious legal and ethical concerns. All things considered, vaccination against a drug of abuse is likely to work best with individuals who are highly motivated to quit using drugs altogether and as part of a comprehensive treatment programme. As such, the medical treatment of drug abuse will not be radically

  5. 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

    Background 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...... treated with innovative medicines and a number of reimbursed medicines. Conclusions Great discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma...

  6. Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

    Directory of Open Access Journals (Sweden)

    Abdulaziz eAl Farsi

    2014-06-01

    Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

  7. Role of First-Line Noninvasive Ventilation in Non-COPD Subjects With Pneumonia.

    Science.gov (United States)

    Rialp, Gemma; Forteza, Catalina; Muñiz, Daniel; Romero, Maria

    2017-09-01

    The use of noninvasive ventilation (NIV) in non-COPD patients with pneumonia is controversial due to its high rate of failure and the potentially harmful effects when NIV fails. The purpose of the study was to evaluate outcomes of the first ventilatory treatment applied, NIV or invasive mechanical ventilation (MV), and to identify predictors of NIV failure. Historical cohort study of 159 non-COPD patients with pneumonia admitted to the ICU with ventilatory support. Subjects were divided into 2 groups: invasive MV or NIV. Univariate and multivariate analyses with demographic and clinical data were performed. Analysis of mortality was adjusted for the propensity of receiving first-line invasive MV. One hundred and thirteen subjects received first-line invasive MV and 46 received first-line NIV, of which 27 needed intubation. Hospital mortality was 35, 37 and 56%, respectively, with no significant differences among groups. In the propensity-adjusted analysis (expressed as OR [95% CI]), hospital mortality was associated with age (1.05 [1.02-1.08]), SAPS3 (1.03 [1.00-1.07]), immunosuppression (2.52 [1.02-6.27]) and NIV failure compared to first-line invasive MV (4.3 [1.33-13.94]). Compared with invasive MV, NIV failure delayed intubation (p=.004), and prolonged the length of invasive MV (p=.007) and ICU stay (p=.001). NIV failure was associated with need for vasoactive drugs (OR 7.8 [95% CI, 1.8-33.2], p=.006). In non-COPD subjects with pneumonia, first-line NIV was not associated with better outcome compared with first-line invasive MV. NIV failure was associated with longer duration of MV and hospital stay, and with increased hospital mortality. The use of vasoactive drugs predicted NIV failure. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance.

    Science.gov (United States)

    Cosme, Angel; Montes, Milagrosa; Ibarra, Begoña; Tamayo, Esther; Alonso, Horacio; Mendarte, Usua; Lizasoan, Jacobo; Herreros-Villanueva, Marta; Bujanda, Luis

    2017-05-14

    To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance. A total of 1034 patients infected by Helicobacter pylori ( H. pylori ) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori -resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori -resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Intention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

  9. Modeling and simulation of maintenance treatment in first-line non-small cell lung cancer with external validation

    International Nuclear Information System (INIS)

    Han, Kelong; Claret, Laurent; Sandler, Alan; Das, Asha; Jin, Jin; Bruno, Rene

    2016-01-01

    Maintenance treatment (MTx) in responders following first-line treatment has been investigated and practiced for many cancers. Modeling and simulation may support interpretation of interim data and development decisions. We aimed to develop a modeling framework to simulate overall survival (OS) for MTx in NSCLC using tumor growth inhibition (TGI) data. TGI metrics were estimated using longitudinal tumor size data from two Phase III first-line NSCLC studies evaluating bevacizumab and erlotinib as MTx in 1632 patients. Baseline prognostic factors and TGI metric estimates were assessed in multivariate parametric models to predict OS. The OS model was externally validated by simulating a third independent NSCLC study (n = 253) based on interim TGI data (up to progression-free survival database lock). The third study evaluated pemetrexed + bevacizumab vs. bevacizumab alone as MTx. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, baseline tumor size, ECOG score, Asian ethnicity, age, and gender were significant covariates in the final OS model. The OS model was qualified by simulating OS distributions and hazard ratios (HR) in the two studies used for model-building. Simulations of the third independent study based on interim TGI data showed that pemetrexed + bevacizumab MTx was unlikely to significantly prolong OS vs. bevacizumab alone given the current sample size (predicted HR: 0.81; 95 % prediction interval: 0.59–1.09). Predicted median OS was 17.3 months and 14.7 months in both arms, respectively. These simulations are consistent with the results of the final OS analysis published 2 years later (observed HR: 0.87; 95 % confidence interval: 0.63–1.21). Final observed median OS was 17.1 months and 13.2 months in both arms, respectively, consistent with our predictions. A robust TGI-OS model was developed for MTx in NSCLC. TTG captures treatment effect. The model successfully predicted the OS outcomes of an independent study based on interim

  10. Modeling and simulation of maintenance treatment in first-line non-small cell lung cancer with external validation.

    Science.gov (United States)

    Han, Kelong; Claret, Laurent; Sandler, Alan; Das, Asha; Jin, Jin; Bruno, Rene

    2016-07-13

    Maintenance treatment (MTx) in responders following first-line treatment has been investigated and practiced for many cancers. Modeling and simulation may support interpretation of interim data and development decisions. We aimed to develop a modeling framework to simulate overall survival (OS) for MTx in NSCLC using tumor growth inhibition (TGI) data. TGI metrics were estimated using longitudinal tumor size data from two Phase III first-line NSCLC studies evaluating bevacizumab and erlotinib as MTx in 1632 patients. Baseline prognostic factors and TGI metric estimates were assessed in multivariate parametric models to predict OS. The OS model was externally validated by simulating a third independent NSCLC study (n = 253) based on interim TGI data (up to progression-free survival database lock). The third study evaluated pemetrexed + bevacizumab vs. bevacizumab alone as MTx. Time-to-tumor-growth (TTG) was the best TGI metric to predict OS. TTG, baseline tumor size, ECOG score, Asian ethnicity, age, and gender were significant covariates in the final OS model. The OS model was qualified by simulating OS distributions and hazard ratios (HR) in the two studies used for model-building. Simulations of the third independent study based on interim TGI data showed that pemetrexed + bevacizumab MTx was unlikely to significantly prolong OS vs. bevacizumab alone given the current sample size (predicted HR: 0.81; 95 % prediction interval: 0.59-1.09). Predicted median OS was 17.3 months and 14.7 months in both arms, respectively. These simulations are consistent with the results of the final OS analysis published 2 years later (observed HR: 0.87; 95 % confidence interval: 0.63-1.21). Final observed median OS was 17.1 months and 13.2 months in both arms, respectively, consistent with our predictions. A robust TGI-OS model was developed for MTx in NSCLC. TTG captures treatment effect. The model successfully predicted the OS outcomes of an independent study

  11. Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three Different First-Line Treatment Modalities in the Last Two Decades: A Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Şeniz Öngören

    2017-12-01

    Full Text Available Objective: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL cases. Materials and Methods: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA was administered in 31 cases, 19 patients received interferon-alpha (INF-α, splenectomy was performed in 16 cases, and rituximab was used in one. Results: Although the highest overall response rate (ORR was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. Conclusion: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.

  12. What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study.

    Science.gov (United States)

    Bakker, J L; Wever, K; van Waesberghe, J H; Beeker, A; Meijers-Heijboer, H; Konings, I R; Verheul, H M W

    2015-12-01

    Despite the extensive clinical experience, it is still under debate to what extent patients with metastatic breast cancer (MBC) benefit from multiple lines of chemotherapy beyond standard first or second line treatment. Selection of patients with MBC who will benefit from treatment is crucial to improve outcome and reduce unnecessary toxicity. In this retrospective study, systemic treatment outcome for patients with metastatic MBC is being evaluated. We evaluated to what extent the clinical benefit of prior chemotherapy can predict the success of a subsequent treatment line. Ninety-one patients treated with chemotherapy for MBC between January 2005 and January 2009 were included in this study. Clinical characteristics of patients, choices of chemotherapy and response at first evaluation of every treatment line was evaluated based on radiologic and clinical data. Patients received multiple systemic cytotoxic and biological (combination) therapies. 30% of these patients received more than five consecutive systemic (combination) treatments. First line chemotherapy was mostly anthracycline-based, followed by taxanes, capecitabine and vinorelbine. The response rate (RR, complete response plus partial response according to RECIST 1.1) decreased from 20% (95% CI 11-28%) upon first line of treatment to 0% upon the fourth line. The clinical benefit rate (combining RR and stable disease) decreased from 85% (95% CI 78-93%) in the first to 54% (95% CI 26-67) upon the fourth line. 24% of the patients with clinical benefit at first evaluation did not receive a subsequent line of treatment when progressive disease occurred, while sixty-one percent of the patients with progressive disease at first evaluation of a treatment did not receive a subsequent line of chemotherapy. When applied, the efficacy of a subsequent line of treatment was similar for patients independent of previous treatment benefit. The clinical benefit at first evaluation from systemic treatment in MBC does not

  13. Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study.

    Science.gov (United States)

    Li, Wenhua; Zhao, Xiaoying; Wang, Huijie; Liu, Xin; Zhao, Xinmin; Huang, Mingzhu; Qiu, Lixin; Zhang, Wen; Chen, Zhiyu; Guo, Weijian; Li, Jin; Zhu, Xiaodong

    2017-06-06

    Maintenance therapy proves to be effective in advanced lung and breast cancer after initial chemotherapy. The purpose of this phase II study was to evaluate the efficacy and safety of Uracil and Tegafur (UFT) maintenance in metastatic gastric cancer patients following the first-line fluorouracil-based chemotherapy. Metastatic gastric cancer patients with stable disease or a better response after the completion of first-line chemotherapy were randomized to oral UFT (360mg/m2 × 2 weeks) every 3 weeks until disease progression/intolerable toxicity or to observation (OBS). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS) and safety. The trial was closed after the interim analysis of the 58 enrolled (120 planned) patients. Median PFS was not improved in the UFT group compared with the OBS group (3.2 months versus 3.6 months, P = 0.752), as well as the median OS (14.2 months for both, P = 0.983). However, subgroup analysis showed that low baseline hemoglobin (maintenance therapy (P = 0.032), while the normal hemoglobin patients benefit from the UFT treatment (P = 0.008). Grade 3 to 4 toxicities in the UFT group were anemia (3.4%), thrombocytopenia (3.4%) and diarrhea (6.9%). This trial did not show superiority of UFT maintenance in non-selected patients responding to fluorouracil-based first-line chemotherapy. The normal hemoglobin level at baseline is a predictive biomarker for favorable patient subsets from the maintenance treatment.

  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. 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.

    Science.gov (United States)

    De Costa, Ayesha; Shet, Anita; Kumarasamy, Nagalingeswaran; Ashorn, Per; Eriksson, Bo; Bogg, Lennart; Diwan, Vinod K

    2010-03-26

    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. 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. 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 antiretrovirals in an Indian context.

  16. A Randomized, Controlled, Multicenter Clinical Trial Comparing Pemetrexed/Cisplatin and Gemcitabine/Cisplatin as First-line Treatment for Advanced Nonsquamous Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2012-10-01

    Full Text Available Background and objective Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC. Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment. Methods The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1 to receive cisplatin plus pemetrexed chemotherapy (PC group or gemcitabine plus cisplatin (GC group every 3 weeks. The primary end point was progression free survival (PFS and the secondary end points included 1 year survival rate, objective response rate (ORR, survival without grade 3/4 toxicity (SWT3/4 and safety profile. Results A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS, the PFS was 168 days (5.6 months vs 140 days (4.7 months (P=0.16, one year survival rate was 50.0% vs 54.9% (P=0.47, ORR was 24.4% vs 14.2% (P=0.06 in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23. In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003. The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia. Conclusion The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

  17. First line management in the public sector

    DEFF Research Database (Denmark)

    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...... in first-line managers’ practice. Answering this question helps to illustrate and understand the degree of professionalism in terms of managers' usage of time....

  18. The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

    Science.gov (United States)

    Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

    2010-01-01

    Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

  19. First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment.

    Science.gov (United States)

    Munier, Francis L; Mosimann, Pascal; Puccinelli, Francesco; Gaillard, Marie-Claire; Stathopoulos, Christina; Houghton, Susan; Bergin, Ciara; Beck-Popovic, Maja

    2017-08-01

    The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. This is a retrospective mono-centric comparative review of consecutive patients. Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2-218.6) and 41.7 months (range 19.6-89.5), respectively. Treatment duration was significantly shorter in the IAC group (pchemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. [Tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors].

    Science.gov (United States)

    Beauchêne, C; Martins-Héricher, J; Denis, D; Martin, L; Maillard, H

    2018-05-04

    Episodes of acquired bradykinin-mediated angioedema due to angiotensin-converting enzyme (ACE) inhibitors may result in fatal outcomes. There is no consensus regarding emergency pharmacological management of these episodes. Treatment options include icatibant and C1INH concentrate. Tranexamic acid is administered for moderate episodes. Its efficacy in the treatment of ACE inhibitor-induced episodes of angioedema is not established. The aim of this retrospective study is to assess the benefits of emergency tranexamic acid administration in the management of ACE inhibitor-induced episodes of angioedema. Retrospective analysis of the medical files of patients who consulted between 2010 and 2016 in two French tertiary care hospitals for a bradykinic angioedema attributed to an ACE treatment. All of them had received tranexamic acid as a first line treatment. Thirty three patients who had experienced severe episode of angioedema were included. Twenty seven patients showed significant improvement when treated with tranexamic acid alone. The six remaining patients were treated with icatibant (5/33) or C1INH concentrate (1/33), due to partial improvement after tranexamic acid therapy. None of the patients were intubated, no fatalities were recorded and no side effects were reported. Tranexamic acid is an easily accessible and affordable therapy that may provide effective treatment for ACE inhibitor-induced episodes of angioedema. It may help while waiting for a more specific treatment (icatibant and C1INH concentrate) that is at times unavailable in emergency departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  1. A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin.

    Science.gov (United States)

    Lubin, V; Shojai, R; Darmon, P; Cosson, E

    2016-06-01

    This study assessed whether myoinositol might be a first-line medical treatment for gestational diabetes mellitus (GDM). For 12 months, women with GDM not controlled by diet (n=32) were prospectively treated with myoinositol 1200mg and folic acid 400μg/day, while consecutive women (n=28) with insulin-requiring GDM treated during the previous year at our centre constituted the control group. Baseline characteristics and care were similar in both groups. Insulin was required in eight women (25%) in the myoinositol group who, compared with the 24 who did not need insulin, were older (37±5 vs. 32±5 years, respectively; P=0.018) and had a larger percentage of high self-monitored glucose values (45±8% vs. 32±14%; P<0.0001) during the week prior to the introduction of myoinositol treatment. All of the women had similar pregnancy outcomes regardless of their GDM management, although less labour induction was required in the myoinositol group (OR: 0.22 [0.07-0.65]), which had no side effects. This pilot study suggests that myoinositol may be a safe first-line medical treatment for uncontrolled GDM. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Stephen Wright

    Full Text Available 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.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.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.Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was

  4. Ketamine as a first-line treatment for severely agitated emergency department patients.

    Science.gov (United States)

    Riddell, Jeff; Tran, Alexander; Bengiamin, Rimon; Hendey, Gregory W; Armenian, Patil

    2017-07-01

    Emergency physicians often need to control agitated patients who present a danger to themselves and hospital personnel. Commonly used medications have limitations. Our primary objective was to compare the time to a defined reduction in agitation scores for ketamine versus benzodiazepines and haloperidol, alone or in combination. Our secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. We conducted a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation. Providers measured agitation levels on a previously validated 6-point sedation scale at 0-, 5-, 10-, and 15-min after receiving sedation. We also assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. 106 patients were enrolled and 98 met eligibility criteria. There was no significant difference between groups in initial agitation scores. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5-, 10-, and 15-min after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. In highly agitated and violent emergency department patients, significantly fewer patients receiving ketamine as a first line sedating agent were agitated at 5-, 10-, and 15-min. Ketamine appears to be faster at controlling agitation than standard emergency department medications. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.

    Science.gov (United States)

    Suaysod, Rapeepan; Ngo-Giang-Huong, Nicole; Salvadori, Nicolas; Cressey, Tim R; Kanjanavanit, Suparat; Techakunakorn, Pornchai; Krikajornkitti, Sawitree; Srirojana, Sakulrat; Laomanit, Laddawan; Chalermpantmetagul, Suwalai; Lallemant, Marc; Le Cœur, Sophie; McIntosh, Kenneth; Traisathit, Patrinee; Jourdain, Gonzague

    2015-07-01

    Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Predictors of early mortality after rabbit antithymocyte globulin as first-line treatment in severe aplastic anemia.

    Science.gov (United States)

    Atta, Elias H; Lima, Carlos B L; Dias, Danielle S P; Clé, Diego V; Bonduel, Mariana M; Sciuccati, Gabriela B; Medeiros, Larissa A; Oliveira, Michel M; Salvino, Marco A; Garanito, Marlene P; Blum Fonseca, Patricia B; Saad, Sara Teresinha O; Calado, Rodrigo T; Scheinberg, Phillip

    2017-11-01

    Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10 9 /L (OR 7.64, P  35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10 9 /L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

  7. Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation

    DEFF Research Database (Denmark)

    Tram Henriksen, Louise; Gottschalk Højfeldt, Sofie; Schmiegelow, Kjeld

    2017-01-01

    BACKGROUND: As pegylated asparaginase is becoming the preferred first-line asparaginase preparation in the chemotherapy regimens of childhood acute lymphoblastic leukemia (ALL), there is a need to evaluate this treatment. METHODS: The aim of this study was to evaluate the pharmacokinetics...... of prolonged upfront biweekly PEG-asparaginase (where PEG is polyethylene glycol) treatment by measuring serum l-asparaginase activity and formation of anti-PEG-asparaginase antibodies. A total of 97 evaluable patients (1-17 years), diagnosed with ALL, and treated according to the NOPHO ALL2008 protocol (where...... NOPHO is Nordic Society of Paediatric Haematology and Oncology) were included. In the NOPHO ALL2008 protocol, patients are randomized to 8 or 15 doses of intramuscular PEG-asparaginase (Oncaspar(®) ) 1,000 IU/m²/dose, at 2-week or 6-week intervals with a total of 30-week treatment (Clinical trials...

  8. Regimen durability in HIV-infected children and adolescents initiating first-line ART in a large public sector HIV cohort in South Africa.

    Science.gov (United States)

    Bonawitz, Rachael; Brennan, Alana T; Long, Lawrence; Heeren, Timothy; Maskew, Mhairi; Sanne, Ian; Fox, Matthew P

    2018-04-15

    In April 2010 tenofovir and abacavir replaced stavudine in public-sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side-effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for pediatric patients 3 to 19 years of age at 8 public sector clinics in Johannesburg, South Africa. Cohort analysis of treatment naïve, non-pregnant pediatric patients from 3 to 19 years old initiated on ART between April 2004-December 2013. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir and/or abacavir was substituted for stavudine after April 2010 in first-line ART. We evaluated the frequency and type of single-drug substitutions, treatment interruptions, and switches to second-line therapy. Fine and Gray competing risk regression models were used to evaluate the association of antiretroviral drug type with single-drug substitutions, treatment interruptions, and second-line switches in the first 24-months on treatment. 398 (15.3%) single-drug substitutions, 187 (7.2%) treatment interruptions and 86 (3.3%) switches to second-line therapy occurred among 2602 pediatric patients over 24-months on ART. Overall, the rate of single-drug substitutions started to increase in 2009, peaked in 2011 at 25%, then declined to 10% in 2013, well after the integration of tenofovir into pediatric regimens; no patients over the age of 3 were initiated on abacavir for first-line therapy. Competing risk regression models showed patients on zidovudine or stavudine had upwards of a 5-fold increase in single-drug substitution vs. patients initiated on tenofovir in the first 24-months on ART. Older adolescents also had a 2-3-fold increase in treatment interruptions and switches to second-line

  9. Reemergence of Splenectomy for ITP Second-line Treatment?

    Science.gov (United States)

    Chater, Charbel; Terriou, Louis; Duhamel, Alain; Launay, David; Chambon, Jean P; Pruvot, François R; Rogosnitzky, Moshe; Zerbib, Philippe

    2016-11-01

    Corticosteroids are still the standard first-line treatment for immune thrombocytopenic purpura (ITP). As second-line therapy, splenectomy and Rituximab are both recommended. The aim of our study was to compare the efficacy of Rituximab to splenectomy in persistent or chronic ITP patients. Between January 1999 and March 2015, we retrospectively selected all consecutive patients who underwent an ITP second-line treatment: Rituximab or splenectomy. The distinction between open (OS) and laparoscopic splenectomy (LS) was analyzed. Primary outcome was composite: hospitalization for bleeding and/or thrombocytopenia and death from hemorrhage or infection. Secondary outcomes were based on response (R) and complete response (CR) rates as defined by the American Society of Hematology. Ninety-six patients were included: 30 patients received Rituximab, 37 underwent OS, and 29 underwent LS. The follow-up was 30, 60, and 120 months in Rituximab, LS, and OS groups, respectively. At 30 month, the primary outcome-free survival rate was higher in splenectomy groups (84% for OS, 86% for LS) than Rituximab group (47%) (P = 0.0002). Similarly, at 30 month, R and CR rates were higher for OS (86.5% and 75.7%, respectively) and LS groups (93.1% and 89.7%) than Rituximab (46.7% and 30%) (P = 0.0001). Moreover, R rates remained elevated at 60 month for OS and LS groups (83.7% and 89.6% respectively) and 78.4% at 120 month for OS group. We observed that splenectomy for ITP second-line treatment was more effective than Rituximab regarding maintenance of R, CR, and overall response rates. OS and LS had similar efficacy.

  10. Cost identification of Nordic FLIRI, Nordic FLOX, XELIRI and XELOX in first-line treatment of advanced colorectal cancer in Sweden -- a clinical practice model approach.

    Science.gov (United States)

    Pettersson, Karin; Carlsson, Göran; Holmberg, Christoffer; Sporrong, Sofia Kälvemark

    2012-09-01

    The role of health-related economy is crucial due to the finite healthcare resources. Intravenous (i.v.) regimes Nordic FLOX and Nordic FLIRI, and the partly oral alternatives XELIRI and XELOX are four commonly used chemotherapies in the first-line treatment of advanced colorectal cancer (CRC) in the Scandinavian countries, all with different costs. To describe and compare costs associated with four commonly used treatments for advanced CRC in clinical routine practice. An additional aim was to evaluate the theoretical cost impact of adverse effects associated with the therapies. The retrospective study was carried out using observations and a clinical quality database of CRC patients treated with Nordic FLOX, Nordic FLIRI, XELIRI and XELOX as first line at an oncology clinic in Gothenburg, Sweden. The treatments are used in parallel in clinical practice. All patients treated from 2003 to 2009 were included. The clinical outcome of the therapies was equivalent; mean treatment time was 5.9-7.7 months. A clinical economic evaluation model was designed. All direct costs associated with the baseline treatment, administration of chemotherapy and drug costs were collected and evaluated. The maximum cost for the four treatments was estimated to be 72 000-75 000 SEK per patient for six months, of this approximately 8000 SEK was linked to treatment of toxicity. During six months the i.v. treatments could include 17 more outpatient visits per patient compared to the oral alternatives. During treatment at the clinic around 20% of the patients were hospitalised (XELOX excluded, because of few included patients). The results indicate that the four regimens are similar in terms of treatment costs. Different costs affect the total cost. The oral alternative makes it possible to treat additional patients with the same labour force resources. Treatment of adverse effects contributes to extensive resource use at the hospital.

  11. First-line tracheal resection and primary anastomosis for postintubation tracheal stenosis.

    Science.gov (United States)

    Elsayed, H; Mostafa, A M; Soliman, S; Shoukry, T; El-Nori, A A; El-Bawab, H Y

    2016-07-01

    Introduction Tracheal stenosis following intubation is the most common indication for tracheal resection and reconstruction. Endoscopic dilation is almost always associated with recurrence. This study investigated first-line surgical resection and anastomosis performed in fit patients presenting with postintubation tracheal stenosis. Methods Between February 2011 and November 2014, a prospective study was performed involving patients who underwent first-line tracheal resection and primary anastomosis after presenting with postintubation tracheal stenosis. Results A total of 30 patients (20 male) were operated on. The median age was 23.5 years (range: 13-77 years). Seventeen patients (56.7%) had had previous endoscopic tracheal dilation, four (13.3%) had had tracheal stents inserted prior to surgery and one (3.3%) had undergone previous tracheal resection. Nineteen patients (63.3%) had had a tracheostomy. Eight patients (26.7%) had had no previous tracheal interventions. The median time of intubation in those developing tracheal stenosis was 20.5 days (range: 0-45 days). The median length of hospital stay was 10.5 days (range: 7-21 days). The success rate for anastomoses was 96.7% (29/30). One patient needed a permanent tracheostomy. The in-hospital mortality rate was 3.3%: 1 patient died from a chest infection 21 days after surgery. There was no mortality or morbidity in the group undergoing first-line surgery for de novo tracheal lesions. Conclusions First-line tracheal resection with primary anastomosis is a safe option for the treatment of tracheal stenosis following intubation and obviates the need for repeated dilations. Endoscopic dilation should be reserved for those patients with significant co-morbidities or as a temporary measure in non-equipped centres.

  12. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study

    NARCIS (Netherlands)

    Hamers, Raph L.; Schuurman, Rob; Sigaloff, Kim C. E.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Wit, Ferdinand W.; van Vugt, Michèle; Stevens, Wendy S.; de Wit, Tobias F. Rinke

    2012-01-01

    Background The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large

  13. Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

    Science.gov (United States)

    Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James

    2017-01-01

    Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. Hormonal therapy followed by chemotherapy or the reverse sequence as first-line treatment of hormone-responsive, human epidermal growth factor receptor-2 negative metastatic breast cancer patients: results of an observational study.

    Science.gov (United States)

    Bighin, Claudia; Dozin, Beatrice; Poggio, Francesca; Ceppi, Marcello; Bruzzi, Paolo; D'Alonzo, Alessia; Levaggi, Alessia; Giraudi, Sara; Lambertini, Matteo; Miglietta, Loredana; Vaglica, Marina; Fontana, Vincenzo; Iacono, Giuseppina; Pronzato, Paolo; Del Mastro, Lucia

    2017-07-04

    Introduction Although hormonal-therapy is the preferred first-line treatment for hormone-responsive, HER2 negative metastatic breast cancer, no data from clinical trials support the choice between hormonal-therapy and chemotherapy.Methods Patients were divided into two groups according to the treatment: chemotherapy or hormonal-therapy. Outcomes in terms of clinical benefit and median overall survival (OS) were retrospectively evaluated in the two groups. To calculate the time spent in chemotherapy with respect to OS in the two groups, the proportion of patients in chemotherapy relative to those present in either group was computed at every day from the start of therapy.Results From 1999 to 2013, 119 patients received first-line hormonal-therapy (HT-first group) and 100 first-line chemotherapy (CT-first group). Patients in the CT-first group were younger and with poorer prognostic factors as compared to those in HT-first group. Clinical benefit (77 vs 81%) and median OS (50.7 vs 51.1 months) were similar in the two groups. Time spent in chemotherapy was significantly longer during the first 3 years in CT-first group (54-34%) as compared to the HT-first group (11-18%). This difference decreased after the third year and overall was 28% in the CT-first group and 18% in the HT-first group.Conclusions The sequence first-line chemotherapy followed by hormonal-therapy, as compared with the opposite sequence, is associated with a longer time of OS spent in chemotherapy. However, despite the poorer prognostic factors, patients in the CT-first group had a superimposable OS than those in the HT-first group.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

    Science.gov (United States)

    Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

    2014-01-01

    A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

  18. 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 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.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%.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.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.

  19. Performance of the first ANTARES detector line

    Energy Technology Data Exchange (ETDEWEB)

    Bruijn, R.; Kooijman, P.; Lim, G.; De Wolf, E. [Univ Amsterdam, Inst Hoge Energiefys, NL-1098 XG Amsterdam, (Netherlands); Ageron, M.; Aubert, J.J.; Bertin, V.; Brunner, J.; Busto, J.; Carr, J.; Coyle, P.; Dornic, D.; Escoffier, S.; Hallewell, G.; Lambard, G.; Lavalle, J.; Lelaizant, G.; Louis, F.; Melissas, M.; Payre, P.; Reed, C. [CPPM, CNRS, IN2P3, F-13288 Marseille 9, (France); Ageron, M.; Aubert, J.J.; Bertin, V.; Brunner, J.; Busto, J.; Carr, J.; Coyle, P.; Dornic, D.; Escoffier, S.; Hallewell, G.; Lambard, G.; Lavalle, J.; Lelaizant, G.; Louis, F.; Melissas, M.; Payre, P.; Reed, C. [Univ Aix Marseille 2, F-13288 Marseille 9, (France); Aguilar, J.A.; Bigongiari, C.; Hernandez-Rey, J.J.; Salesa, F.; Toscano, S.; Zornoza, J.D.; Zuniga, J. [Univ Valencia, CSIC, IFIC Inst Fis Corpuscular, Edificios Invest Paterna, Valencia 46071, (Spain); Albert, A.; Castel, D.; Drouhin, D.; Ernenwein, J.P.; Guillard, G. [Univ Houte Alsace, GRPHE, F-68093 Mulhouse, (France); Anton, G.; Auer, R.; Eberl, T.; Fehr, F.; Graf, K.; Hossl, J.; Kalekin, O.; Kappes, A.; Katz, U.; Kopper, C.; Kretschmer, W.; Kuch, S.; Lahmann, R.; Laschinsky, H.; Loucatos, S.; Motz, H.; Naumann, C.; Ostasch, R.; Richardt, C.; Schoeck, F.; Shanidze, R. [Univ Erlangen Nurnberg, Inst Phys, D-91058 Erlangen, (Germany); Anvar, S.; Druillole, F.; Lamare, P.; Le Provost, H. [CEA Saclay, Direct Sci Mat, Inst Rech Fondamentales Univers, Serv Elect Detecteurs et Informat, F-91191 Gif Sur Yvette, (France)

    2009-07-01

    In this paper we report on the data recorded with the first Antares detector line. The line was deployed on 14 February 2006 and was connected to the readout 2 weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first 6 months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived. (authors)

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

    DEFF Research Database (Denmark)

    Rasmussen, Mads Heilskov; Jensen, Niels; Tarpgaard, Line Schmidt

    2013-01-01

    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...... 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...... 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...

  1. New modalities (setting, fractionation) of radioimmunotherapy by 90Y-ibritumomab tiuxetan (90Y zevalin) in first line treatment of follicular type non Hodgkin malignant lymphomas: efficiency, toxicity and personalized dosimetry approach

    International Nuclear Information System (INIS)

    Morschhauser, F.

    2008-12-01

    Rationale: radioimmunotherapy (R.I.T.) with 90 Y-ibritumomab tiuxetan ([ 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 [ 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 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 Zevalin in patient

  2. 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 ...

  3. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

  4. Factors that facilitate registered nurses in their first-line nurse manager role.

    Science.gov (United States)

    Cziraki, Karen; McKey, Colleen; Peachey, Gladys; Baxter, Pamela; Flaherty, Brenda

    2014-11-01

    To determine the factors that attract and retain Registered Nurses in the first-line nurse manager role. The first-line nurse manger role is pivotal in health-care organisations. National demographics suggest that Canada will face a first-line nurse manager shortage because of retirement in the next decade. Determination of factors that attract and retain Registered Nurses will assist organisations and policy makers to employ strategies to address this shortage. The study used an exploratory, descriptive qualitative approach, consisting of semi-structured individual interviews with 11 Registered Nurses in first-line nurse manager roles. The findings revealed a discrepancy between the factors that attract and retain Registered Nurses in the first-line nurse manager role, underscored the importance of the mentor role and confirmed the challenges encountered by first-line nurse managers practicing in the current health-care environment. The first-line nurse manager role has been under studied. Further research is warranted to understand which strategies are most effective in supporting first-line nurse managers. Strategies to support nurses in the first-line nurse manager role are discussed for the individual, programme, organisation and health-care system/policy levels. © 2013 John Wiley & Sons Ltd.

  5. Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

    Directory of Open Access Journals (Sweden)

    S De Groot

    Full Text Available Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC. Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs.Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013. The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness.In current daily practice, 54% (336/621 of all patients was treated with targeted therapies. Most patients (84%; 282/336 received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336 also received second-line therapy; the majority was treated with everolimus (40%, 40/101 or sorafenib (28%, 28/101. Current treatment practice (including patients not receiving targeted therapy led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285 was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy. This improvement is completely driven by the health

  6. 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.

  7. Clinical Observation of Icotinib Hydrochloride in First-line Therapy 
for Pulmonary Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Xinjie YANG

    2013-07-01

    Full Text Available Background and objective It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Results Among the 56 patients, the tumor objective response rate (ORR and disease control rate (DCR was 46.4% (26/56 and 78.6% (46/56, respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18, DCR was 94.4% (17/18 respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (P<0.05. The most common drug-related adverse events were mild skin rash (28.5% and diarrhea (12%. Conclusion Single agent treatment with icotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

  8. Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis.

    Science.gov (United States)

    Kaplan-Messas, Audrey; Barkana, Yaniv; Avni, Isaac; Neumann, Ron

    2003-06-01

    To evaluate the clinical experience with methotrexate as a first-line corticosteroid-sparing drug in patients with resistant ocular inflammation. We retrospectively studied 39 consecutive patients with uveitis (n = 36) or scleritis (n = 3) who were treated with methotrexate following inadequate control with corticosteroids lasting five years. Criteria for initiating treatment with methotrexate and defining outcome were strictly defined. The cohort included 21 females and 18 males, all Caucasians, with a mean age of 26.6 years (range: 3-73 years). Patients were followed up for 21.5 +/- 12.6 months. Treatment was discontinued due to side effects in 10 patients (26%). Of the remaining 29 patients, full or partial control of inflammation was achieved in 23 (79%). Response to treatment was observed after a mean of 2.4 +/- 0.8 months. Ten patients were fully controlled and discontinued methotrexate therapy after a mean of 20.9 +/- 9.2 months, with no recurrence of inflammation. Use of topical and systemic corticosteroids was markedly reduced in responsive patients. Methotrexate is recommended as a first-line adjunct to or replacement of systemic corticosteroids in the treatment of ocular inflammation.

  9. Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Samsuddin Khan

    2014-07-01

    Full Text Available Background: There are limited data on the failure of second-line antiretroviral therapy (ART and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62% responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0. No serious treatment-related adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL

  10. Caring behaviour perceptions from nurses of their first-line nurse managers.

    Science.gov (United States)

    Peng, Xiao; Liu, Yilan; Zeng, Qingsong

    2015-12-01

    Nursing is acknowledged as being the art and science of caring. According to the theory of nursing as caring, all persons are caring but not every behaviour of a person is caring. Caring behaviours in the relationship between first-line nurse managers and Registered Nurses have been studied to a lesser extent than those that exist between patients and nurses. Caring behaviour of first-line nurse managers from the perspective of Registered Nurses is as of yet unknown. Identifying caring behaviours may be useful as a reference for first-line nurse managers caring for nurses in a way that nurses prefer. To explore first-line nurse managers' caring behaviours from the perspective of Registered Nurses in mainland China. Qualitative study, using descriptive phenomenological approach. Fifteen Registered Nurses recruited by purposive sampling method took part in in-depth interviews. Data were analysed according to Colaizzi's technique. Three themes of first-line nurse managers' caring behaviours emerged: promoting professional growth, exhibiting democratic leadership and supporting work-life balance. A better understanding of the first-line nurse managers' caring behaviours is recognised. The three kinds of behaviours have significant meaning to nurse managers. Future research is needed to describe what first-line nurse managers can do to promote nurses' professional growth, increase the influence of democratic leadership, as well as support their work-life balance. © 2015 Nordic College of Caring Science.

  11. Homeopathy in the Age of Antimicrobial Resistance: Is It a Viable Treatment for Upper Respiratory Tract Infections?

    Science.gov (United States)

    Fixsen, Alison

    2018-05-01

     Acute upper respiratory tract infections (URTIs) and their complications are the most frequent cause of antibiotic prescribing in primary care. With multi-resistant organisms proliferating, appropriate alternative treatments to these conditions are urgently required. Homeopathy presents one solution; however, there are many methods of homeopathic prescribing. This review of the literature considers firstly whether homeopathy offers a viable alternative therapeutic solution for acute URTIs and their complications, and secondly how such homeopathic intervention might take place.  Critical review of post 1994 clinical studies featuring homeopathic treatment of acute URTIs and their complications. Study design, treatment intervention, cohort group, measurement and outcome were considered. Discussion focused on the extent to which homeopathy is used to treat URTIs, rate of improvement and tolerability of the treatment, complications of URTIs, prophylactic and long-term effects, and the use of combination versus single homeopathic remedies.  Multiple peer-reviewed studies were found in which homeopathy had been used to treat URTIs and associated symptoms (cough, pharyngitis, tonsillitis, otitis media, acute sinusitis, etc.). Nine randomised controlled trials (RCTs) and 8 observational/cohort studies were analysed, 7 of which were paediatric studies. Seven RCTs used combination remedies with multiple constituents. Results for homeopathy treatment were positive overall, with faster resolution, reduced use of antibiotics and possible prophylactic and longer-term benefits.  Variations in size, location, cohort and outcome measures make comparisons and generalisations concerning homeopathic clinical trials for URTIs problematic. Nevertheless, study findings suggest at least equivalence between homeopathy and conventional treatment for uncomplicated URTI cases, with fewer adverse events and potentially broader therapeutic outcomes. The use of non

  12. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Shen YW

    2016-02-01

    Full Text Available Yan-Wei Shen,* Xiao-Man Zhang,* Shu-Ting Li, Meng Lv, Jiao Yang, Fan Wang, Zhe-Ling Chen, Bi-Yuan Wang, Pan Li, Ling Chen, Jin Yang Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Background and objective: Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation.Patients and methods: Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1.Results: Among the 35 patients, the tumor objective response rate (ORR and disease control rate were 62.9% (22/35 and 88.6% (31/35, respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months, and median overall survival was 21.0 months (95% CI: 20.1–21.9 months. The most common drug-related toxicities were rashes (eleven patients and diarrhea (nine patients, but these were generally manageable and reversible.Conclusion: Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. Keywords: lung neoplasms, icotinib hydrochloride, first-line treatment

  13. On-Chip Dielectrophoretic Separation and Concentration of Viable, Non-Viable and Viable but Not Culturable (VBNC) Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Packard, M M; Shusteff, M; Alocilja, E C

    2012-04-12

    Although bacterial culture remains the gold standard for detection of viable bacteria in environmental specimens, the typical time requirement of twenty-four hours can delay and even jeopardize appropriate public health intervention. In addition, culture is incapable of detecting viable but not culturable (VBNC) species. Conversely, nucleic acid and antibody-based methods greatly decrease time to detection but rarely characterize viability of the bacteria detected. Through selection by membrane permeability, the method described in this work employs positive dielectrophoresis (pDEP) for separation and purification of viable and VBNC species from water and allows concentration of bacteria for downstream applications.

  14. Case Reports of Idiopathic Thrombocytopenia Unresponsive to First-Line Therapies Treated With Traditional Herbal Medicines Based on Syndrome Differentiation.

    Science.gov (United States)

    Yang, Juno; Lee, Beom-Joon; Lee, Jun-Hwan

    The objective of our study is to present two cases showing the effects of traditional Korean herbal medicines based on traditional Korean medicine (TKM) for the treatment of immune thrombocytopenic purpura (ITP). One patient showed no response to treatment with steroids and an immunosuppressive agent. Moreover, liver toxicity and side effects of steroids were evident. However, after he ceased conventional treatment and started to take an herbal medicine, his liver function normalized and the steroid side effects resolved. Ultimately, he achieved complete remission. Another patient with ITP had sustained remission after steroid therapy in childhood, but extensive uterine bleeding and thrombocytopenia recurred when she was 16 years old. She was managed with steroids again for 2 years, but severe side effects occurred, and eventually she ceased taking steroids. She refused a splenectomy, and was then treated with a herbal medicine for 7 months, ultimately leading to sustained remission again. Many patients with resistance to first-line treatments tend to be reluctant to undergo a splenectomy, considered a standard second-line treatment. In conclusion, herbal medicines, based on TKM, may offer alternative treatments for persistent or chronic ITP that is resistant to existing first-line treatments. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for malaria in children in Guinea-Bissau

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik; Rodrigues, Amabelia; Aaby, Peter

    2006-01-01

    BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo...... sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later. METHODS: Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine...

  16. Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies

    Directory of Open Access Journals (Sweden)

    Felger Ingrid

    2005-11-01

    Full Text Available Abstract Background Systematic surveillance for resistant malaria shows high level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP across eastern and southern parts of Africa. This study assessed in vivo SP efficacy after two years of use as an interim first-line drug in Tanzania, and determined the rates of treatment failures obtained after 14 and 28 days of follow-up. Methods The study was conducted in the Ipinda, Mlimba and Mkuranga health facilities in Tanzania. Children aged 6–59 months presenting with raised temperature associated exclusively with P. falciparum (1,000–100,000 parasites per μl were treated with standard dose of SP. Treatment responses were classified according to the World Health Organization (WHO definition as Adequate Clinical and Parasitological Response (ACPR, Early Treatment Failure (ETF, Late Clinical Failure (LCF and Late Parasitological Failure (LPF on day 14 and day 28. Results Overall 196 (85.2% of 230 patients had ACPR on day 14 but only 116 (50.9% on day 28 (57.7% after excluding new infections by parasite genotyping. Altogether 21 (9.1% and 13 (5.7% of the 230 patients assessed up to day 14 and 39 (17.1% and 55 (24.1% of the 228 followed up to day 28 had clinical and parasitological failure, respectively. Conclusion These findings indicate that SP has low therapeutic value in Tanzania. The recommendation of changing first line treatment to artemether + lumefantrine combination therapy from early next year is, therefore, highly justified. These findings further stress that, for long half-life drugs such as SP, establishment of cut-off points for policy change in high transmission areas should consider both clinical and parasitological responses beyond day 14.

  17. Viable Techniques, Leontief’s Closed Model, and Sraffa’s Subsistence Economies

    Directory of Open Access Journals (Sweden)

    Alberto Benítez

    2014-11-01

    Full Text Available This paper studies the production techniques employed in economies that reproduce themselves. Special attention is paid to the distinction usually made between those that do not produce a surplus and those that do, which are referred to as first and second class economies, respectively. Based on this, we present a new definition of viable economies and show that every viable economy of the second class can be represented as a viable economy of the first class under two different forms, Leontief‘s closed model and Sraffa’s subsistence economies. This allows us to present some remarks concerning the economic interpretation of the two models. On the one hand, we argue that the participation of each good in the production of every good can be considered as a normal characteristic of the first model and, on the other hand, we provide a justification for the same condition to be considered a characteristic of the second model. Furthermore, we discuss three definitions of viable techniques advanced by other authors and show that they differ from ours because they admit economies that do not reproduce themselves completely.

  18. A combination of direct viable count and fluorescence in situ hybridization for specific enumeration of viable Lactobacillus delbrueckii subsp.bulgaricus and Streptococcus thermophilus.

    Science.gov (United States)

    García-Hernández, J; Moreno, Y; Amorocho, C M; Hernández, M

    2012-03-01

    We have developed a direct viable count (DVC)-FISH procedure for quickly and easily discriminating between viable and nonviable cells of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains, the traditional yogurt bacteria. direct viable count method has been modified and adapted for Lact. delbrueckii subsp. bulgaricus and Strep. thermophilus analysis by testing different times of incubation and concentrations of DNA-gyrase inhibitors. DVC procedure has been combined with fluorescent in situ hybridization (FISH) for the specific detection of viable cells of both bacteria with specific rRNA oligonucleotide probes (DVC-FISH). Of the four antibiotics tested (novobiocin, nalidixic acid, pipemidic acid and ciprofloxacin), novobiocin was the most effective for DVC method and the optimum incubation time was 7 h for both bacteria. The number of viable cells was obtained by the enumeration of specific hybridized cells that were elongated at least twice their original length for Lactobacillus and twice their original size for Streptococcus. This technique was successfully applied to detect viable cells in inoculated faeces. Results showed that this DVC-FISH procedure is a quick and culture-independent useful method to specifically detect viable Lact. delbrueckii subsp. bulgaricus and Strep. thermophilus in different samples, being applied for the first time to lactic acid bacteria. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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. Copyright© Ferrata Storti Foundation.

  1. Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

    Science.gov (United States)

    Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

    2016-01-01

    This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

  2. Underreporting of side effects of standard first-line ART in the routine ...

    African Journals Online (AJOL)

    Malawi Medical Journal; 23(4): 116-118 December 2011. Side effects of standard first line in ART 116. Underreporting of side effects of standard first-line. ART in the routine setting in Blantyre, Malawi. Abstract. Introduction. In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of ...

  3. Incidence and predictors of severe anemia in Asian HIV-infected children using first-line antiretroviral therapy

    NARCIS (Netherlands)

    Bunupuradah, Torsak; Kariminia, Azar; Chan, Kwai-Cheng; Ramautarsing, Reshmie; Huy, Bui Vu; Han, Ning; Nallusamy, Revathy; Hansudewechakul, Rawiwan; Saphonn, Vonthanak; Sirisanthana, Virat; Chokephaibulkit, Kulkanya; Kurniati, Nia; Kumarasamy, Nagalingeswaran; Yusoff, Nik Khairulddin Nik; Razali, Kamarul; Fong, Siew Moy; Sohn, Annette H.; Lumbiganon, Pagakrong

    2013-01-01

    There are limited data on treatment-related anemia in Asian HIV-infected children. Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had pre-existing severe anemia at baseline were excluded. Anemia was graded using

  4. 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) 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 was still crucial in achieving

  5. A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis

    Directory of Open Access Journals (Sweden)

    Rachita Dhurat

    2018-01-01

    Full Text Available The Conidiobolus coronatus-related rhinoentomophthoromycosis in immunocompetent and immunocompromised (HIV negative individuals has been treated successfully with antifungal drugs. However, C. coronatus infections in first-line antiretroviral therapy (ART-resistant (HIV infected individuals particularly with rhinoentomophthoromycosis have not been reported previously. Here, we describe a case of itraconazole non-responding rhinoentomophthoromycosis in an HIV-infected patient with first-line antiretroviral (ART drug resistance which was successfully managed through systematic diagnostic and therapeutic approaches in dermatologic setting. A 32-year-old HIV-1-infected man presented with painless swelling, nasal redness and respiratory difficulty. The patient was receiving first-line ART and had a history of traumatic injury before the onset of nasopharyngeal manifestations. The patient's previous history included oral candidiasis and pulmonary tuberculosis.

  6. First study on the formation and resuscitation of viable but nonculturable state and beer spoilage capability of Lactobacillus lindneri.

    Science.gov (United States)

    Liu, Junyan; Li, Lin; Li, Bing; Peters, Brian M; Deng, Yang; Xu, Zhenbo; Shirtliff, Mark E

    2017-06-01

    This study aimed to investigate the spoilage capability of Lactobacillus lindneri during the induction and resuscitation of viable but nonculturable (VBNC) state. L. lindneri strain was identified by sequencing the PCR product (amplifying 16S rRNA gene) using ABI Prism 377 DNA Sequencer. During the VBNC state induction by low temperature storage and beer adaption, total, culturable, and viable cells were assessed by acridine orange direct counting, plate counting, and Live/Dead BacLight bacterial viability kit, respectively. Organic acids and diacetyl concentration were measured by reversed-phase high performance liquid chromatography and head dpace gas chromatography, respectively. VBNC state of L. lindneri was successfully induced by both beer adaption and low temperature storage, and glycerol frozen stock was the optimal way to maintain the VBNC state. Addition of catalase was found to be an effective method for the resuscitation of VBNC L. lindneri cells. Furthermore, spoilage capability remained similar during the induction and resuscitation of VBNC L. lindneri. This is the first report of induction by low temperature storage and resuscitation of VBNC L. lindneri strain, as well as the first identification of spoilage capability of VBNC and resuscitated L. lindneri cells. This study indicated that the potential colonization of L. lindneri strain in brewery environment, formation and resuscitation of VBNC state, as well as maintenance in beer spoilage capability, may be an important risk factor for brewery environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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

  8. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-01-01

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  9. Tibia Shaft Fractures in Adolescents: How and When Can They be Managed Successfully With Cast Treatment?

    Science.gov (United States)

    Ho, Christine A

    2016-06-01

    Despite the increasing popularity of operative treatment in adolescent tibia fractures, casting remains a viable first-line treatment. Because the selection bias in published reports does not allow direct comparison between casting and flexible nail treatment of closed pediatric tibia fractures, it is unclear whether flexible nailing offers any advantages over casting. This overview discusses parameters of acceptable alignment, indications, techniques for successful reduction and casting, subsequent inpatient and outpatient management including wedging of casted tibia fractures, expected outcomes, and comparison of casting with flexible nailing. As with any orthopaedic procedure, careful attention to patient selection, indications, and detail facilitates successful cast treatment in this older pediatric population.

  10. The Japanese and the American First-Line Supervisor.

    Science.gov (United States)

    Bryan, Leslie A., Jr.

    1982-01-01

    Compares the American and Japanese first-line supervisor: production statistics, supervisory style, company loyalty, management style, and communication. Also suggests what Americans might learn from the Japanese methods. (CT)

  11. Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation

    Directory of Open Access Journals (Sweden)

    Xiao Zhao

    2014-01-01

    Full Text Available Objective: This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. Patients and Methods: This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV lung adenocarcinoma with epidermal growth factor receptor (EGFR-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS. Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. Results: The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Conclusion: Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

  12. 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 C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    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. 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) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in 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], pfailure 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.

  13. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2-11.8 months), and median overall survival was 21.0 months (95% CI: 20.1-21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

  14. Coal liquefaction becomes viable

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-11-15

    In 2003 the May/June issue of CoalTrans International speculated that coal liquefaction would become viable due to falling coal prices. This has not proved the case but the sustained high oil price is sparking new interest. A survey by Energy Intelligence and Marketing Research during November 2005 revealed a growth in the number of projects under development or at the feasibility stage. The article reports projects in China, the USA, Australia, New Zealand, the Philippines and India. China is commissioning the first wave of large liquefaction plants. The key question is whether other countries, particularly the USA, will follow.

  15. HIV-1 drug resistance genotyping from antiretroviral therapy (ART naïve and first-line treatment failures in Djiboutian patients

    Directory of Open Access Journals (Sweden)

    Elmi Abar Aden

    2012-10-01

    Full Text Available Abstract In this study we report the prevalence of antiretroviral drug resistant HIV-1 genotypes of virus isolated from Djiboutian patients who failed first-line antiretroviral therapy (ART and from ART naïve patients. Patients and methods A total of 35 blood samples from 16 patients who showed first-line ART failure (>1000 viral genome copies/ml and 19 ART-naïve patients were collected in Djibouti from October 2009 to December 2009. Both the protease (PR and reverse transcriptase (RT genes were amplified and sequenced using National Agency for AIDS Research (ANRS protocols. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping. Results Among the 16 patients with first-line ART failure, nine (56.2% showed reverse transcriptase inhibitor-resistant HIV-1 strains: two (12.5% were resistant to nucleoside (NRTI, one (6.25% to non-nucleoside (NNRTI reverse transcriptase inhibitors, and six (37.5% to both. Analysis of the DNA sequencing data indicated that the most common mutations conferring drug resistance were M184V (38% for NRTI and K103N (25% for NNRTI. Only NRTI primary mutations K101Q, K103N and the PI minor mutation L10V were found in ART naïve individuals. No protease inhibitor resistant strains were detected. In our study, we found no detectable resistance in ∼ 44% of all patients who experienced therapeutic failure which was explained by low compliance, co-infection with tuberculosis and malnutrition. Genotyping revealed that 65.7% of samples were infected with subtype C, 20% with CRF02_AG, 8.5% with B, 2.9% with CRF02_AG/C and 2.9% with K/C. Conclusion The results of this first study about drug resistance mutations in first-line ART failures show the importance of performing drug resistance mutation test which guides the choice of a second-line regimen. This will improve the management of HIV-infected Djiboutian patients. Virtual slides The virtual slide(s for this article can be found

  16. A budget-impact and cost-effectiveness model for second-line treatment of major depression.

    Science.gov (United States)

    Malone, Daniel C

    2007-07-01

    Depressed patients who initially fail to achieve remission when placed on a selective serotonin reuptake inhibitor (SSRI) may require a second treatment. The purpose of this study was to evaluate the effectiveness, cost, cost-effectiveness, and budget impact of second-line pharmacologic treatment for major depressive disorder (MDD). A cost-effectiveness analysis was conducted to evaluate second-line therapies (citalopram, escitalopram, fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, and venlafaxine extended release [XR]) for the treatment of depression. Effectiveness data were obtained from published clinical studies. The primary outcome was remission defined as a score of 7 or less on the Hamilton Rating Scale for Depression (HAM-D) or a score of 10 or less on the montgomery-Asberg Depression Rating Scale (MADRS) depression rating scales. The wholesale acquisition cost (WAC) for medications and medical treatment costs for depression were included. The perspective was derived from a managed care organization (MCO) with 500,000 members, a 1.9% annual incidence of depression, and treatment duration of 6 months. Assumptions included: second-line treatment is not as effective as first-line treatment, WAC price reflects MCO costs, and side effects were identical. Sensitivity analyses were conducted to determine variables that influenced the results. Second-line remission rates were 20.4% for venlafaxine XR, 16.9% for sertraline, 16.4% for escitalopram, 15.1% for generic SSRIs (weighted average), and 13.6% for paroxetine CR. Pharmacy costs ranged from $163 for generic SSRIs to $319 for venlafaxine SR. Total cost per patient achieving remission was $14,275 for venlafaxine SR, followed by $16,100 for escitalopram. The incremental cost-effectiveness ratio (ICER) for venlafaxine SR compared with generic SSRIs was $2,073 per patient achieving remission, followed by escitalopram with an ICER of $3,566. The model was most sensitive to other therapies

  17. Separation of viable and non-viable tomato (Solanum lycopersicum L.) seeds using single seed near-infrared spectroscopy

    DEFF Research Database (Denmark)

    Shrestha, Santosh; Deleuran, Lise Christina; Gislum, René

    2017-01-01

    Single seed near-infrared (NIR) spectroscopy is a non-destructive technology commonly used for predicting lipids, proteins, carbohydrates and water content of agricultural products. The aim of the current study is to investigate the prospects of NIR spectroscopy in classifying viable and non...... identified as important for classification of viable and non-viable tomato seeds by iPLS-DA. The sensitivity i.e. ability to correctly identify the positive samples and specificity i.e. ability to reject the negative samples of the (iPLS-DA) model on identified spectral regions for prediction of viable......-viable tomato seeds of two cultivars using chemometrics. The data exploration were performed by principal component analysis (PCA). Subsequently, viable and non-viable seeds were classified by partial least squares-discriminant analysis (PLS-DA) and interval PLS-DA (iPLS-DA). The indication of clustering...

  18. Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.

    Science.gov (United States)

    Chouaid, Christos; Luciani, Laura; LeLay, Katell; Do, Pascal; Bennouna, Jaafar; Perol, Maurice; Moro-Sibilot, Denis; Vergnenègre, Alain; de Pouvourville, Gérard

    2017-10-01

    The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  19. Resilience and Work-life Balance in First-line Nurse Manager

    OpenAIRE

    Kim, Miyoung; Windsor, Carol

    2015-01-01

    Purpose: 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. Methods: 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. Results: Analysis revealed that participants perceived work-life balance a...

  20. Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

    Science.gov (United States)

    Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

    2018-05-01

    The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

  1. Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute

    International Nuclear Information System (INIS)

    Hainsworth, John D; Thompson, Dana S; Bismayer, John A; Gian, Victor G; Merritt, William M; Whorf, Robert C; Finney, Lindsey H; Dudley, B Stephens

    2015-01-01

    This trial compared the efficacy and toxicity of standard first-line treatment with paclitaxel/carboplatin versus paclitaxel/carboplatin plus sorafenib in patients with advanced ovarian carcinoma. Patients with stage 3 or 4 epithelial ovarian cancer with residual measurable disease or elevated CA-125 levels after maximal surgical cytoreduction were randomized (1:1) to receive treatment with paclitaxel (175 mg/m 2 , 3 h infusion, day 1) and carboplatin (AUC 6.0, IV, day 1) with or without sorafenib 400 mg orally twice daily (PO BID). Patients were reevaluated for response after completing 6 weeks of treatment (two cycles); responding or stable patients received six cycles of paclitaxel/carboplatin. Patients receiving the sorafenib-containing regimen continued sorafenib (400 PO BID) for a total of 52 weeks. Eighty-five patients were randomized and received treatment.Efficacy was similar for patients receiving paclitaxel/carboplatin/sorafenib versus paclitaxel/carboplatin: overall response rates 69% versus 74%; median progression-free survival 15.4 versus 16.3 months; 2 year survival 76% versus 81%. The addition of sorafenib added substantially to the toxicity of the regimen; rash, hand–foot syndrome, mucositis, and hypertension were significantly more common in patients treated with sorafenib. The addition of sorafenib to standard paclitaxel/carboplatin did not improve efficacy and substantially increased toxicity in the first-line treatment of advanced epithelial ovarian cancer. Based on evidence from this study and other completed trials, sorafenib is unlikely to have a role in the treatment of ovarian cancer

  2. Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer.

    Science.gov (United States)

    Bogdanowicz, Brian S; Hoch, Matthew A; Hartranft, Megan E

    2017-04-01

    Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.

  3. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

    Science.gov (United States)

    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

  4. Single center experience with endoscopic subureteral dextranomer/hyaluronic acid injection as first line treatment in 1,551 children with intermediate and high grade vesicoureteral reflux.

    Science.gov (United States)

    Puri, Prem; Kutasy, Balazs; Colhoun, Eric; Hunziker, Manuela

    2012-10-01

    In recent years the endoscopic injection of dextranomer/hyaluronic acid has become an established alternative to long-term antibiotic prophylaxis and the surgical management of vesicoureteral reflux. We determined the safety and effectiveness of the endoscopic injection of dextranomer/hyaluronic acid as first line treatment for high grade vesicoureteral reflux. Between 2001 and 2010, 1,551 children (496 male, 1,055 female, median age 1.6 years) underwent endoscopic correction of intermediate and high grade vesicoureteral reflux using dextranomer/hyaluronic acid soon after the diagnosis of vesicoureteral reflux on initial voiding cystourethrogram. Vesicoureteral reflux was unilateral in 761 children and bilateral in 790. Renal scarring was detected in 369 (26.7%) of the 1,384 patients who underwent dimercapto-succinic acid imaging. Reflux grade in the 2,341 ureters was II in 98 (4.2%), III in 1,340 (57.3%), IV in 818 (34.9%) and V in 85 (3.6%). Followup ultrasound and voiding cystourethrogram were performed 3 months after the outpatient procedure, and renal ultrasound was performed annually thereafter. Patients were followed for 3 months to 10 years (median 5.6 years). Vesicoureteral reflux resolved after the first, second and third endoscopic injection of dextranomer/hyaluronic acid in 2,039 (87.1%), 264 (11.3%) and 38 (1.6%) ureters, respectively. Febrile urinary tract infections developed during followup in 69 (4.6%) patients. None of the patients in the series needed reimplantation of ureters or experienced any significant complications. Our results confirm the safety and efficacy of the endoscopic injection of dextranomer/hyaluronic acid in the eradication of high grade vesicoureteral reflux. We recommend this 15-minute outpatient procedure as the first line of treatment for high grade vesicoureteral reflux. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study

    International Nuclear Information System (INIS)

    Lee, Su Jin; Kim, Sungmin; Kim, Moonjin; Lee, Jeeyun; Park, Yeon Hee; Im, Young-Hyuck; Park, Se Hoon

    2015-01-01

    The aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma. Patients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1–14 capecitabine 1000 mg/m 2 twice daily + D1 cisplatin 75 mg/m 2 , every 3 weeks) or the CP arm (D1–14 capecitabine 1000 mg/m 2 twice daily + D1, 8 paclitaxel 80 mg/m 2 , every 3 weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life. A total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1–14) and the response rates were 57 and 58 % in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23 months, the median PFS was 5.1 months (95 % CI 4.0–6.2 months) in the cisplatin arm and 6.7 months (95 % CI 4.9–8.5 months) in the paclitaxel arm, whereas the median OS was 10.5 months (95 % CI 9.2–11.9 months) in the cisplatin arm and 13.2 months (95 % CI 9.4–17.0 months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms. Both CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma

  6. Primordial germ cell-mediated chimera technology produces viable pure-line Houbara bustard offspring: potential for repopulating an endangered species.

    Directory of Open Access Journals (Sweden)

    Ulrich Wernery

    2010-12-01

    Full Text Available The Houbara bustard (Chlamydotis undulata is a wild seasonal breeding bird populating arid sandy semi-desert habitats in North Africa and the Middle East. Its population has declined drastically during the last two decades and it is classified as vulnerable. Captive breeding programmes have, hitherto, been unsuccessful in reviving population numbers and thus radical technological solutions are essential for the long term survival of this species. The purpose of this study was to investigate the use of primordial germ cell-mediated chimera technology to produce viable Houbara bustard offspring.Embryonic gonadal tissue was dissected from Houbara bustard embryos at eight days post-incubation. Subsequently, Houbara tissue containing gonadal primordial germ cells (gPGCs was injected into White Leghorn chicken (Gallus gallus domesticus embryos, producing 83/138 surviving male chimeric embryos, of which 35 chimeric roosters reached sexual maturity after 5 months. The incorporation and differentiation of Houbara gPGCs in chimeric chicken testis were assessed by PCR with Houbara-specific primers and 31.3% (5/16 gonads collected from the injected chicken embryos showed the presence of donor Houbara cells. A total of 302 semen samples from 34 chimeric roosters were analyzed and eight were confirmed as germline chimeras. Semen samples from these eight roosters were used to artificially inseminate three female Houbara bustards. Subsequently, 45 Houbara eggs were obtained and incubated, two of which were fertile. One egg hatched as a male live born Houbara; the other was female but died before hatching. Genotyping confirmed that the male chick was a pure-line Houbara derived from a chimeric rooster.This study demonstrates for the first time that Houbara gPGCs can migrate, differentiate and eventually give rise to functional sperm in the chimeric chicken testis. This approach may provide a promising tool for propagation and conservation of endangered avian

  7. Risk Factors for Incident Diabetes in a Cohort Taking First-Line Nonnucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy.

    Science.gov (United States)

    Karamchand, Sumanth; Leisegang, Rory; Schomaker, Michael; Maartens, Gary; Walters, Lourens; Hislop, Michael; Dave, Joel A; Levitt, Naomi S; Cohen, Karen

    2016-03-01

    Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

  8. Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

    Science.gov (United States)

    Romero Acuña, L; Langhi, M; Pérez, J; Romero Acuña, J; Machiavelli, M; Lacava, J; Vallejo, C; Romero, A; Fasce, H; Ortiz, E; Grasso, S; Amato, S; Rodríguez, R; Barbieri, M; Leone, B

    1999-01-01

    To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

  9. 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.

  10. A new approach in the first-line treatment of bacterial and mycotic vulvovaginitis with topical lipohydroperoxides and glycyrrhetic acid: a comparative study.

    Science.gov (United States)

    Mainini, G; Rotondi, M; Scaffa, C

    2011-01-01

    PURPOSE OF INVESTIGATIONS: The aim of this randomized controlled trial was to evaluate efficacy and tolerability of a new association of lipohydroperoxides and glycyrrhetic acid on topical treatment of bacterial and mycotic vulvovaginitis. One hundred consecutive patients with bacterial or mycotic vulvovaginitis were randomly assigned to a study group treated with vaginal lipohydroperoxides and a derivative of glycyrrhetic acid for three days (n = 50), and a control group using vaginal antibacterial metronidazole (500 mg) or antimycotic econazole (150 mg) for six days (n = 50). A clinical and microbiological response was achieved in 80.4% and 88.9% in investigational and control group, respectively (p > 0.05). Compared to traditional antimicrobial drugs, the effect appears to be faster and safer, even if not significantly. The 6-month recurrence rate was 7.7% and 5.6% in the investigational and control group, respectively. Topical medication based on lipohydroperoxides and glycyrrhetic acid showed a clinical and microbiological efficacy in the first-line treatment of bacterial and mycotic vulvovaginitis, comparable to conventional drugs.

  11. High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa.

    Directory of Open Access Journals (Sweden)

    Justen Manasa

    Full Text Available To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.Cross-sectional study nested within HIV treatment programme.Adult (≥ 18 years HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART regimen and with evidence of virological failure (one viral load >1000 copies/ml were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%; and stavudine, lamivudine and nevirapine (24%. Median duration of ART was 42 months (interquartile range (IQR 32-53 and median duration of antiretroviral failure was 27 months (IQR 17-40. One hundred and ninety one (86% had at least one drug resistance mutation. For 34 individuals (15%, the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR 5.70, 95% confidence interval (CI 2.60-12.49.There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

  12. Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

    Science.gov (United States)

    Semvua, Hadija H; Mtabho, Charles M; Fillekes, Quirine; van den Boogaard, Jossy; Kisonga, Riziki M; Mleoh, Liberate; Ndaro, Arnold; Kisanga, Elton R; van der Ven, Andre; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Burger, David M

    2013-01-01

    To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

  13. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. ... The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab ...

  14. The Budget Impact of Including Necitumumab on the Formulary for First-Line Treatment of Metastatic Squamous Non-Small Cell Lung Cancer: U.S. Commercial Payer and Medicare Perspectives.

    Science.gov (United States)

    Bly, Christopher A; Molife, Cliff; Brown, Jacqueline; Tawney, Mahesh K; Carter, Gebra Cuyun; Cinfio, Frank N; Klein, Robert W

    2018-06-01

    Necitumumab (Neci) was the first biologic approved by the FDA for use in combination with gemcitabine and cisplatin (Neci + GCis) in first-line treatment of metastatic squamous non-small cell lung cancer (msqNSCLC). The potential financial impact on a health plan of adding Neci + GCis to drug formularies may be important to value-based decision makers in the United States, given ever-tightening budget constraints. To estimate the budget impact of introducing Neci + GCis for first-line treatment of msqNSCLC from U.S. commercial and Medicare payer perspectives. The budget impact model estimates the costs of msqNSCLC before and after adoption of Neci + GCis in hypothetical U.S. commercial and Medicare health plans over a 3-year time horizon. The eligible patient population was estimated from U.S. epidemiology statistics. Clinical data were obtained from randomized clinical trials, U.S. prescribing information, and clinical guidelines. Market share projections were based on market research data. Cost data were obtained from online sources and published literature. The incremental aggregate annual health plan, per-patient-per-year (PPPY), and per-member-per-month (PMPM) costs were estimated in 2015 U.S. dollars. One-way sensitivity analyses were conducted to assess the effect of model parameters on results. In a hypothetical 1,000,000-member commercial health plan with an estimated population of 30 msqNSCLC patients receiving first-line chemotherapy, the introduction of Neci + GCis at an initial market share of approximately 5% had an overall year 1 incremental budget impact of $88,394 ($3,177 PPPY, $0.007 PMPM), representing a 2.9% cost increase and reaching $304,079 ($10,397 PPPY, $0.025 PMPM) or a 7.4% cost increase at a market share of 14.7% in year 3. This increase in total costs was largely attributable to Neci drug costs and, in part, due to longer survival and treatment duration for patients treated with Neci+GCis. Overall, treatment costs increased by $81

  15. Endovascular Treatment of Phlegmasia Cerulea Dolens with Impending Venous Gangrene: Manual Aspiration Thrombectomy as the First-Line Thrombus Removal Method

    International Nuclear Information System (INIS)

    Oguzkurt, Levent; Ozkan, Ugur; Demirturk, Orhan S.; Gur, Serkan

    2011-01-01

    Purpose: Our purpose was to report the outcome of endovascular treatment with manual aspiration thrombectomy as the first-line thromboablative method for phlegmasia cerulea dolens. Methods: Between October 2006 and May 2010, seven consecutive patients (5 women, 2 men; age range, 31–80 years) with the diagnosis of phlegmasia cerulea dolens secondary to acute iliofemoral deep venous thrombosis had endovascular treatment with manual aspiration thrombectomy. Catheter-directed thrombolysis and stent placement were used as adjunctive procedures. Phlegmasia was left-sided in five and right-sided in two patients. Results: All patients had associated great saphenous vein thrombosis in addition to iliofemoral deep vein thrombosis (DVT). Aspiration thrombectomy completely removed the thrombus from the popliteal vein to the inferior vena cava (IVC) in all cases. Three patients with May-Thurner syndrome had stent placement in the left common iliac vein. Two patients had early recurrences. Repeated aspiration thrombectomy was unsuccessful in one patient. There were no complications related to the procedure. One patient who had been successfully treated died of sepsis and another patient who had unsuccessful repeated interventions had below-the-knee amputation. Overall, the clinical success and survival rates of patients in this study were 86%. On follow-up, three patients with successful treatment were asymptomatic with no deep venous insufficiency. One of these patients died during the 4-month follow-up period. Two patients had mild ankle swelling with deep venous insufficiency. Conclusions: Manual aspiration thrombectomy with adjunctive use of catheter-directed thrombolysis and stent placement is an effective endovascular treatment method with high clinical success and survival rates for phlegmasia cerulean dolens.

  16. First line treatment response in patients with transmitted HIV drug resistance and well defined time point of HIV infection: updated results from the German HIV-1 seroconverter study.

    Directory of Open Access Journals (Sweden)

    Fabia Zu Knyphausen

    Full Text Available BACKGROUND: Transmission of drug-resistant HIV-1 (TDR can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. METHODS: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. RESULTS: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667 in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0% and decreased significantly over time (OR = 0.92, CI = 0.87-0.98, p = 0.01. Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92-1.09, p = 0.96 and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17 remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41. CONCLUSION: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were

  17. The Conceptual Mechanism for Viable Organizational Learning Based on Complex System Theory and the Viable System Model

    Science.gov (United States)

    Sung, Dia; You, Yeongmahn; Song, Ji Hoon

    2008-01-01

    The purpose of this research is to explore the possibility of viable learning organizations based on identifying viable organizational learning mechanisms. Two theoretical foundations, complex system theory and viable system theory, have been integrated to provide the rationale for building the sustainable organizational learning mechanism. The…

  18. 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

  19. Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting.

    Directory of Open Access Journals (Sweden)

    Amy P Abernethy

    Full Text Available To establish a baseline for care and overall survival (OS based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC without common actionable mutations.Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015. Patients with documented epidermal growth factor receptor (EGFR or anaplastic lymphoma kinase (ALK translocation were excluded. Anti-cancer drug therapy and overall survival were described overall, and by histology.A total of 2,014 patients with stage IV NSCLC without known EGFR or ALK genomic tumor aberrations initiated systemic anticancer therapy, 22% with squamous and 78% with nonsquamous histology. Their mean (SD age was 67 (10 years, 55% were male, and 87% had a smoking history. In nonsquamous NSCLC, carboplatin plus pemetrexed either without (25.7% or with bevacizumab (16% were the most common regimens; 26.6% of nonsquamous patients receiving induction therapy also received continuation maintenance therapy. In squamous NSCLC, carboplatin plus paclitaxel (37.6% or nab-paclitaxel (21.1% were the most commonly used regimens. Overall median OS was 9.7 months (95% CI: 9.1, 10.3, 8.5 months (95% CI: 7.4, 10.0 for squamous, and 10.0 months (95% CI: 9.4, 10.8 for nonsquamous NSCLC.The results provide context for evaluating the effect of shifting treatment patterns of NSCLC treatments on patient outcomes, and for community oncology benchmarking initiatives.

  20. Novel Approach for Enterocutaneous Fistula Treatment with the Use of Viable Cryopreserved Placental Membrane

    Directory of Open Access Journals (Sweden)

    Frederick Nichols

    2016-01-01

    Full Text Available Enterocutaneous fistulas (ECF are a difficult and costly surgical complication to manage. The standard treatment of nil per os (NPO and total paraenteral nutrition (TPN is not well tolerated by patients. TPN is also known for complications associated with long term central venous catheterization and for high cost of prolonged hospital stay. We present two low output ECF cases successfully treated with viable cryopreserved placental membrane (vCPM placed into the fistula tracts. One patient is a 59-year-old male with a low output ECF from a jejunostomy tube site four weeks after the surgery. The second patient is an 87-year-old male with a low output ECF following a small bowel resection secondary to a strangulated inguinal hernia. He was evaluated on day 41 after surgery. NPO and TPN for several weeks did not resolute the ECF. The fistulae were closed postoperatively in both patients with zero output on the same day after one vCPM application. On day 3 postoperatively both patients were started on clear liquid diets and subsequently advanced to regular diets. The ECF have remained resolved for over 2 months. The use of vCPM is a novel promising approach for treatment of ECF.

  1. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

    Science.gov (United States)

    Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert

    2016-01-01

    WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8) compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2) compared to the public sector. This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Polymerase chain reaction-based discrimination of viable from non-viable Mycoplasma gallisepticum

    Directory of Open Access Journals (Sweden)

    Ching Giap Tan

    2014-09-01

    Full Text Available The present study was based on the reverse transcription polymerase chain reaction (RT-PCR of the 16S ribosomal nucleic acid (rRNA of Mycoplasma for detection of viable Mycoplasma gallisepticum. To determine the stability of M. gallisepticum 16S rRNA in vitro, three inactivation methods were used and the suspensions were stored at different temperatures. The 16S rRNA of M. gallisepticum was detected up to approximately 20–25 h at 37 °C, 22–25 h at 16 °C, and 23–27 h at 4 °C. The test, therefore, could detect viable or recently dead M. gallisepticum (< 20 h. The RT-PCR method was applied during an in vivo study of drug efficacy under experimental conditions, where commercial broiler-breeder eggs were inoculated with M. gallisepticum into the yolk. Hatched chicks that had been inoculated in ovo were treated with Macrolide 1. The method was then applied in a flock of day 0 chicks with naturally acquired vertical transmission of M. gallisepticum, treated with Macrolide 2. Swabs of the respiratory tract were obtained for PCR and RT-PCR evaluations to determine the viability of M. gallisepticum. This study proved that the combination of both PCR and RT-PCR enables detection and differentiation of viable from non-viable M. gallisepticum.

  4. Accurate line intensities of methane from first-principles calculations

    Science.gov (United States)

    Nikitin, Andrei V.; Rey, Michael; Tyuterev, Vladimir G.

    2017-10-01

    In this work, we report first-principle theoretical predictions of methane spectral line intensities that are competitive with (and complementary to) the best laboratory measurements. A detailed comparison with the most accurate data shows that discrepancies in integrated polyad intensities are in the range of 0.4%-2.3%. This corresponds to estimations of the best available accuracy in laboratory Fourier Transform spectra measurements for this quantity. For relatively isolated strong lines the individual intensity deviations are in the same range. A comparison with the most precise laser measurements of the multiplet intensities in the 2ν3 band gives an agreement within the experimental error margins (about 1%). This is achieved for the first time for five-atomic molecules. In the Supplementary Material we provide the lists of theoretical intensities at 269 K for over 5000 strongest transitions in the range below 6166 cm-1. The advantage of the described method is that this offers a possibility to generate fully assigned exhaustive line lists at various temperature conditions. Extensive calculations up to 12,000 cm-1 including high-T predictions will be made freely available through the TheoReTS information system (http://theorets.univ-reims.fr, http://theorets.tsu.ru) that contains ab initio born line lists and provides a user-friendly graphical interface for a fast simulation of the absorption cross-sections and radiance.

  5. A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

    DEFF Research Database (Denmark)

    Knapper, Steven; Russell, Nigel; Gilkes, Amanda

    2017-01-01

    The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activ...

  6. OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer

    Science.gov (United States)

    Zhang, Pengfei; Hutton, David; Li, Qiu

    2018-01-01

    Objectives Erlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although it has improved progression-free survival (PFS), overall survival (OS) was limited and erlotinib can be expensive. This cost-effectiveness analysis compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy. Setting First-line treatment of Asian patients with NSCLC with EGFR mutation. Methods A Markov model was created based on the results of the ENSURE (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and chemotherapy. The model simulates cancer progression and all causes of death. All medical costs were calculated from the perspective of the Chinese healthcare system. Main outcome measures The primary outcomes are costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results The combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy, respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16 months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most influential factors were the health utility of PFS, the cost of erlotinib and the health utility of progressed disease. Conclusion Erlotinib monotherapy may be acceptable as a cost-effective first-line treatment for NSCLC compared with gemcitabine-based chemotherapy. The results were robust to changes in assumptions. Trial registration number NCT01342965 and CTONG-0802. PMID:29654023

  7. High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

    Science.gov (United States)

    Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

    2015-01-01

    Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

  8. 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...

  9. Endoscopic Injection of Dextranomer/Hyaluronic Acid as First-Line Treatment in 851 Consecutive Children with High-Grade Vesicoureteral Reflux: Efficacy and Long-Term Results.

    Science.gov (United States)

    Friedmacher, Florian; Colhoun, Eric; Puri, Prem

    2018-03-15

    Endoscopic injection of dextranomer/hyaluronic is widely acknowledged as first-line treatment of lower grade vesicoureteral reflux. Our objective was to demonstrate its long-term efficacy and safety in eradicating high-grade reflux. Eight-hundred-fifty-one children (518 girls, 333 boys), median age 2.3 years (2 months-13.7 years), underwent endoscopic correction of high-grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units: grade IV in 1,153 (89.6%) and grade V in 134 (10.4%). 99m technetium-dimercaptosuccinic acid imaging identified renal scarring in 317 (37.3%) patients. Follow-up ultrasound and voiding cystourethrogram were performed 3 months post intervention and renal ultrasound annually thereafter. Median follow-up was 8.5 years (6 months-16 years). Overall resolution rate after the first endoscopic injection was 895/1,287 (69.5%): 70.4% in grade IV and 61.9% in grade V, respectively. Reflux resolved after a second injection in 259 (20.1%) and after a third in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in infants reflux resolution, 43 (5.1%) children developed febrile urinary tract infections: 24 (55.8%) in the first, 15 (34.9%) in the second and 4 (9.3%) after ≥3 years. Of these, 6 had reflux recurrence and 8 demonstrated neocontralateral grade III reflux, which was successfully treated with single endoscopic injection of dextranomer/hyaluronic acid. Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long-term treatment for grade IV and V vesicoureteral reflux, which can be easily repeated in cases of failure with a high subsequent resolution rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Gated Treatment Delivery Verification With On-Line Megavoltage Fluoroscopy

    International Nuclear Information System (INIS)

    Tai An; Christensen, James D.; Gore, Elizabeth; Khamene, Ali; Boettger, Thomas; Li, X. Allen

    2010-01-01

    Purpose: To develop and clinically demonstrate the use of on-line real-time megavoltage (MV) fluoroscopy for gated treatment delivery verification. Methods and Materials: Megavoltage fluoroscopy (MVF) image sequences were acquired using a flat panel equipped for MV cone-beam CT in synchrony with the respiratory signal obtained from the Anzai gating device. The MVF images can be obtained immediately before or during gated treatment delivery. A prototype software tool (named RTReg4D) was developed to register MVF images with phase-sequenced digitally reconstructed radiograph images generated from the treatment planning system based on four-dimensional CT. The image registration can be used to reposition the patient before or during treatment delivery. To demonstrate the reliability and clinical usefulness, the system was first tested using a thoracic phantom and then prospectively in actual patient treatments under an institutional review board-approved protocol. Results: The quality of the MVF images for lung tumors is adequate for image registration with phase-sequenced digitally reconstructed radiographs. The MVF was found to be useful for monitoring inter- and intrafractional variations of tumor positions. With the planning target volume contour displayed on the MVF images, the system can verify whether the moving target stays within the planning target volume margin during gated delivery. Conclusions: The use of MVF images was found to be clinically effective in detecting discrepancies in tumor location before and during respiration-gated treatment delivery. The tools and process developed can be useful for gated treatment delivery verification.

  11. Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02).

    Science.gov (United States)

    Tahara, M; Kiyota, N; Yokota, T; Hasegawa, Y; Muro, K; Takahashi, S; Onoe, T; Homma, A; Taguchi, J; Suzuki, M; Minato, K; Yane, K; Ueda, S; Hara, H; Saijo, K; Yamanaka, T

    2018-04-01

    The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. The PCE regimen shows promising

  12. HIGH-n HYDROGEN RECOMBINATION LINES FROM THE FIRST GALAXIES

    International Nuclear Information System (INIS)

    Rule, E.; Loeb, A.; Strelnitski, V. S.

    2013-01-01

    We investigate the prospects of blind and targeted searches in the radio domain (10 MHz to 1 THz) for high-n hydrogen recombination lines from the first generation of galaxies, at z ∼ 4 km s –1 , allow us to assess the blind search time necessary for detection by a given facility. We show that the chances for detection are the highest in the millimeter and submillimeter domains, but finding spontaneous emission in a blind search, especially from redshifts z >> 1, is a challenge even with powerful facilities, such as the Actama Large Millimeter/Submillimeter Array and Square Kilometre Array. The probability of success is higher for a targeted search of lines with principal quantum number n ∼ 10 in Lyman-break galaxies amplified by gravitational lensing. Detection of more than one hydrogen line in such a galaxy will allow for line identification and a precise determination of the galaxy's redshift

  13. Primordial Germ Cell-Mediated Chimera Technology Produces Viable Pure-Line Houbara Bustard Offspring: Potential for Repopulating an Endangered Species

    Science.gov (United States)

    Wernery, Ulrich; Liu, Chunhai; Baskar, Vijay; Guerineche, Zhor; Khazanehdari, Kamal A.; Saleem, Shazia; Kinne, Jörg; Wernery, Renate

    2010-01-01

    Background The Houbara bustard (Chlamydotis undulata) is a wild seasonal breeding bird populating arid sandy semi-desert habitats in North Africa and the Middle East. Its population has declined drastically during the last two decades and it is classified as vulnerable. Captive breeding programmes have, hitherto, been unsuccessful in reviving population numbers and thus radical technological solutions are essential for the long term survival of this species. The purpose of this study was to investigate the use of primordial germ cell-mediated chimera technology to produce viable Houbara bustard offspring. Methodology/Principal Findings Embryonic gonadal tissue was dissected from Houbara bustard embryos at eight days post-incubation. Subsequently, Houbara tissue containing gonadal primordial germ cells (gPGCs) was injected into White Leghorn chicken (Gallus gallus domesticus) embryos, producing 83/138 surviving male chimeric embryos, of which 35 chimeric roosters reached sexual maturity after 5 months. The incorporation and differentiation of Houbara gPGCs in chimeric chicken testis were assessed by PCR with Houbara-specific primers and 31.3% (5/16) gonads collected from the injected chicken embryos showed the presence of donor Houbara cells. A total of 302 semen samples from 34 chimeric roosters were analyzed and eight were confirmed as germline chimeras. Semen samples from these eight roosters were used to artificially inseminate three female Houbara bustards. Subsequently, 45 Houbara eggs were obtained and incubated, two of which were fertile. One egg hatched as a male live born Houbara; the other was female but died before hatching. Genotyping confirmed that the male chick was a pure-line Houbara derived from a chimeric rooster. Conclusion This study demonstrates for the first time that Houbara gPGCs can migrate, differentiate and eventually give rise to functional sperm in the chimeric chicken testis. This approach may provide a promising tool for propagation

  14. Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010.

    Science.gov (United States)

    Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; Dimeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

    2014-05-01

    improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.

  15. 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.

  16. Managerial competence of first-line nurse managers: A concept analysis.

    Science.gov (United States)

    Gunawan, Joko; Aungsuroch, Yupin

    2017-02-01

    A variety of terms are used interchangeably to define managerial competence of first-line nurse managers. This has resulted in a degree of ambiguity in the way managerial competence is described. The aim of this concept analysis is to clarify what is meant by managerial competence of first-line nurse managers internationally, what attributes signify it, and what its antecedents and consequences are. The Walker and Avant concept analysis approach was applied. The attributes of managerial competence include developing self, planning, organizing, leading, managing legal and ethical issues, and delivering health care. Antecedents to managerial competence include internal and external factors. Consequences include nurse performances, nurse and patient outcomes, intention to stay of nurses, and nurse and patient satisfaction. This analysis helps first-line nurse managers to understand the concept and determine where the responsibility lies in establishing a definition of managerial competence. It is recommended that middle and top managers should be aware of the internal and external factors as antecedents of the concept. Further research is needed to illuminate the attributes of managerial competence in relation to antecedents and the potential effect upon the consequences, and the need to establish managerial competence evaluation. © 2017 John Wiley & Sons Australia, Ltd.

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

    Science.gov (United States)

    Joshi, Beena; Chauhan, Sanjay; Pasi, Achhelal; Kulkarni, Ragini; Sunil, Nithya; Bachani, Damodar; Mankeshwar, Ranjit

    2014-07-01

    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. 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. 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). 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Trojan J

    2016-09-01

    Full Text Available Jörg Trojan, Oliver Waidmann Medizinische Klinik 1, Universitätsklinikum Frankfurt, Germany Abstract: Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC. In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months. Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1 blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. Keywords: hepatocellular carcinoma, receptor tyrosine kinase inhibitor, sorafenib, regorafenib, lenvatinib, tivantinib, cabozantinib, ramucirumab, immunotherapy, anti-CTLA-4, anti-PD-1, oncolytic virus

  20. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.

    Directory of Open Access Journals (Sweden)

    Nay Thiha

    Full Text Available WHO recommends that stavudine is phased out of antiretroviral therapy (ART programmes and replaced with tenofovir (TDF for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment.Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR to identify associated factors using log binomial regression.Of 4934 patients tested, 4324 (87% had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8 compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2 compared to the public sector.This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.

  1. Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.

    Science.gov (United States)

    Dragovic, Gordana; Smith, Colette J; Jevtovic, Djordje; Dimitrijevic, Bozana; Kusic, Jovana; Youle, Mike; Johnson, Margaret A

    2016-03-03

    The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens.

  2. 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 mR...

  3. Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

    Directory of Open Access Journals (Sweden)

    George G. Zhanel

    2016-01-01

    Full Text Available Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR E. coli. Resistance to fosfomycin in E. coli is rare (100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin’s in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.

  4. Epirubicin plus paclitaxel regimen as second-line treatment of patients with small-cell lung cancer.

    Science.gov (United States)

    Pasello, Giulia; Carli, Paolo; Canova, Fabio; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Urso, Loredana; Conte, Pierfranco; Favaretto, Adolfo

    2015-04-01

    Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. The aim of this study was to describe activity and safety of second-line with epirubicin at 70 mg/m(2) followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of six cycles. This is a retrospective review of all patients with SCLC evaluated for second-line treatment between 2003 and 2013 at our Institution. Sixty-eight patients received the study regimen of epirubicin with paclitaxel. We observed partial response in 19 (30%), stable disease in 22 (34%) and total early failure rate in 23 (36%) patients. Median progression free and overall survival were 21.8 and 26.5 weeks, respectively. Haematological toxicities were as follows: grade 3-4 leukopenia and neutropenia in 18 (31%) and 30 (22%) of patients, respectively; grade 3 anaemia and grade 4 thrombocytopenia were reported in 2 (3%) and 5 (9%) of patients, respectively. Epirubicin with paclitaxel is an active and tolerable second-line regimen in patients with SCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Second-Line Treatment Options in Non-Small-Cell Lung Cancer: Report From an International Experts Panel Meeting of the Italian Association of Thoracic Oncology

    NARCIS (Netherlands)

    Gridelli, Cesare; Baas, Paul; Barlesi, Fabrice; Ciardiello, Fortunato; Crinò, Lucio; Felip, Enriqueta; Gadgeel, Shirish; Papadimitrakopoulou, Vali; Paz-Ares, Luis; Planchard, David; Perol, Maurice; Hanna, Nasser; Sgambato, Assunta; Casaluce, Francesca; de Marinis, Filippo

    2017-01-01

    Non-small-cell lung cancer (NSCLC) patients inevitably progress to first-line therapy and further active treatments are warranted. In the past few years, new second-line therapies, beyond chemotherapy agents, have become available in clinical practice. To date, several options for the second-line

  6. The efficacy of levofloxacin-based triple therapy for first-line Helicobacter pylori eradication

    Directory of Open Access Journals (Sweden)

    Yusuf Aydın

    2011-06-01

    Full Text Available Standard triple therapy composed of a proton pump inhibitor, clarithromycin and amoxicillin has been widely preferred for H. pylori eradication in Turkey and World. Alternative therapies are currently under investigation because of an increase in clarithromycin resistance. The aim of this study was to evaluate the efficacy of a levoflox-acin-containing triple therapy.Materials and methods: The study was carried out in 81 H. pylori-infected patients (52 female, 29 male with nonul-cer dyspepsia. The mean age was found 46.3 ± 13.9. Treatment was indicated with lansoprazol 30 mg b.d., amoxicil-lin 1 g b.d., and levofloxacin 500 mg daily for 7 days. H. pylori status was rechecked by (14C urea breath test 6-8 weeks after the end of therapy.Results: Totally 81 patients could complete the treatment and follow-up protocol. Effectiveness was 68%. The distrib-tions of age, gender and smoking were similar between eradicated and non-eradicated groups (p > 0.05.Conclusion: Seven-day levofloxacin based triple therapy is not very effective in the first-line treatment of H. pylori in-fection. The new treatment modalities should be investigated.

  7. Pharmacokinetics of first-line tuberculosis drugs in tanzanian patients

    NARCIS (Netherlands)

    Tostmann, A.; Mtabho, C.M.; Semvua, H.H.; Boogaard, J. van den; Kibiki, G.S.; Boeree, M.J.; Aarnoutse, R.E.

    2013-01-01

    East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling.

  8. Factors contributing to managerial competence of first-line nurse managers: A systematic review.

    Science.gov (United States)

    Gunawan, Joko; Aungsuroch, Yupin; Fisher, Mary L

    2018-02-01

    To determine the factors contributing to managerial competence of first-line nurse managers. Understanding factors affecting managerial competence of nurse managers remains important to increase the performance of organizations; however, there is sparse research examining factors that influence managerial competence of first-line nurse managers. Systematic review. The search strategy was conducted from April to July 2017 that included 6 electronic databases: Science Direct, PROQUEST Dissertations and Theses, MEDLINE, CINAHL, EMBASE, and Google Scholar for the years 2000 to 2017 with full text in English. Quantitative and qualitative research papers that examined relationships among managerial competence and antecedent factors were included. Quality assessment, data extractions, and analysis were completed on all included studies. Content analysis was used to categorize factors into themes. Eighteen influencing factors were examined and categorized into 3 themes-organizational factors, characteristics and personality traits of individual managers, and role factors. Findings suggest that managerial competence of first-line nurse managers is multifactorial. Further research is needed to develop strategies to develop managerial competence of first-line nurse managers. © 2017 John Wiley & Sons Australia, Ltd.

  9. Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

    Science.gov (United States)

    Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

    2017-02-07

    Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

  10. On the use of the serial dilution culture method to enumerate viable phytoplankton in natural communities of plankton subjected to ballast water treatment.

    Science.gov (United States)

    Cullen, John J; MacIntyre, Hugh L

    2016-01-01

    Discharge standards for ballast water treatment (BWT) systems are based on concentrations of living cells, for example, as determined with vital stains. Ultraviolet radiation (UV) stops the reproduction of microorganisms without killing them outright; they are living, but not viable, and ecologically as good as dead. Consequently, UV-treated discharge can be compliant with the intent of regulation while failing a live/dead test. An alternative evaluation of BWT can be proposed based on the assessment of viable, rather than living, cells in discharge water. In principle, the serial dilution culture-most probable number (SDC-MPN) method provides the appropriate measure for phytoplankton. But, the method has been criticized, particularly because it is thought that many phytoplankton species cannot be cultured. A review of the literature shows that although SDC-MPN has been used for more than 50 years-generally to identify and count phytoplankton species that cannot be preserved-its application to enumerate total viable phytoplankton seems to be new, putting past criticisms of the method in a different light. Importantly, viable cells need to grow only enough to be detected, not to be brought into sustained culture, and competition between species in a dilution tube is irrelevant as long as the winner is detectable. Thorough consideration of sources of error leads to recommendations for minimizing and quantifying uncertainties by optimizing growth conditions and conducting systematic comparisons. We conclude that with careful evaluation, SDC-MPN is potentially an effective method for assessing the viability of phytoplankton after BWT.

  11. Estimating quality adjusted progression free survival of first-line treatments for EGFR mutation positive non small cell lung cancer patients in The Netherlands

    Directory of Open Access Journals (Sweden)

    Verduyn S

    2012-09-01

    Full Text Available Abstract Background Gefitinib, a tyrosine kinase inhibitor, is an effective treatment in advanced non-small cell lung cancer (NSCLC patients with an activating mutation in the epidermal growth factor receptor (EGFR. Randomised clinical trials showed a benefit in progression free survival for gefitinib versus doublet chemotherapy regimens in patients with an activated EGFR mutation (EGFR M+. From a patient perspective, progression free survival is important, but so is health-related quality of life. Therefore, this analysis evaluates the Quality Adjusted progression free survival of gefitinib versus three relevant doublet chemotherapies (gemcitabine/cisplatin (Gem/Cis; pemetrexed/cisplatin (Pem/Cis; paclitaxel/carboplatin (Pac/Carb in a Dutch health care setting in patients with EGFR M+ stage IIIB/IV NSCLC. This study uses progression free survival rather than overall survival for its time frame in order to better compare the treatments and to account for the influence that subsequent treatment lines would have on overall survival analysis. Methods Mean progression free survival for Pac/Carb was obtained by extrapolating the median progression free survival as reported in the Iressa-Pan-Asia Study (IPASS. Data from a network meta-analysis was used to estimate the mean progression free survival for therapies of interest relative to Pac/Carb. Adjustment for health-related quality of life was done by incorporating utilities for the Dutch population, obtained by converting FACT-L data (from IPASS to utility values and multiplying these with the mean progression free survival for each treatment arm to determine the Quality Adjusted progression free survival. Probabilistic sensitivity analysis was carried out to determine 95% credibility intervals. Results The Quality Adjusted progression free survival (PFS (mean, (95% credibility interval was 5.2 months (4.5; 5.8 for Gem/Cis, 5.3 months (4.6; 6.1 for Pem/Cis; 4.9 months (4.4; 5.5 for Pac/Carb and 8

  12. Treatment of Helicobacter pylori infection 2011.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    This article reviews the literature published pertaining to Helicobacter pylori eradication over the last year. The general perception among clinicians and academics engaged in research on H. pylori has been that eradication rates for first-line therapies are falling, although some data published this year have cast doubt on this. The studies published this year have therefore focussed on developing alternative strategies for the first-line eradication of H. pylori. In this regard, clear evidence now exists that both levofloxacin and bismuth are viable options for first-line therapy. The sequential and "concomitant" regimes have also been studied in new settings and may have a role in future algorithms also. In addition, data have emerged that the probiotic Saccharomyces boulardii may be a useful adjunct to antibiotic therapy. Other studies promote individualized therapies based on host polymorphisms, age, and other such demographic factors.

  13. The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

    Science.gov (United States)

    Bozkaya, Yakup; Doğan, Mutlu; Yazıcı, Ozan; Erdem, Gökmen Umut; Demirci, Nebi Serkan; Zengin, Nurullah

    2017-01-01

    Alpha-fetoprotein producing gastric carcinoma (AFP-PGC) is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF) as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC) were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001). A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001). Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%), and 82.2% (complete response - 3%, PR - 36.2%, SD - 43%) in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively). Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area. PMID:28273032

  14. The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Yakup Bozkaya

    2017-05-01

    Full Text Available Alpha-fetoprotein producing gastric carcinoma (AFP-PGC is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001. A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001.Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%, and 82.2% (complete response - 3%, PR - 36.2%, SD - 43% in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively. Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area.

  15. Vinorelbine as first-line chemotherapy for metastatic breast carcinoma.

    Science.gov (United States)

    Romero, A; Rabinovich, M G; Vallejo, C T; Perez, J E; Rodriguez, R; Cuevas, M A; Machiavelli, M; Lacava, J A; Langhi, M; Romero Acuña, L

    1994-02-01

    A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

  16. First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

    Science.gov (United States)

    Frenay, M P; Fontaine, D; Vandenbos, F; Lebrun, C

    2005-09-01

    At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.

  17. Longitudinal Analysis of Adherence to First-Line Antiretroviral Therapy: Evidence of Treatment Sustainability from an Indian HIV Cohort.

    Science.gov (United States)

    Shet, Anita; Kumarasamy, N; Poongulali, Selvamuthu; Shastri, Suresh; Kumar, Dodderi Sunil; Rewari, Bharath B; Arumugam, Karthika; Antony, Jimmy; De Costa, Ayesha; D'Souza, George

    2016-01-01

    Given the chronic nature of HIV infection and the need for life-long antiretroviral therapy (ART), maintaining long-term optimal adherence is an important strategy for maximizing treatment success. In order to understand better the dynamic nature of adherence behaviors in India where complex cultural and logistic features prevail, we assessed the patterns, trajectories and time-dependent predictors of adherence levels in relation to virological failure among individuals initiating first-line ART in India. Between July 2010 and August 2013, eligible ART-naïve HIV-infected individuals newly initiating first-line ART within the national program at three sites in southern India were enrolled and monitored for two years. ART included zidovudine/stavudine/tenofovir plus lamivudine plus nevirapine/efavirenz. Patients were assessed using clinical, laboratory and adherence parameters. Every three months, medication adherence was measured using pill count, and a structured questionnaire on adherence barriers was administered. Optimal adherence was defined as mean adherence ≥95%. Statistical analysis was performed using a bivariate and a multivariate model of all identified covariates. Adherence trends and determinants were modeled as rate ratios using generalized estimating equation analysis in a Poisson distribution. A total of 599 eligible ART-naïve patients participated in the study, and contributed a total of 921 person-years of observation time. Women constituted 43% and mean CD4 count prior to initiating ART was 192 cells/mm3. Overall mean adherence among all patients was 95.4%. The proportion of patients optimally adherent was 75.6%. Predictors of optimal adherence included older age (≥40 years), high school-level education and beyond, lower drug toxicity-related ART interruption, full disclosure, sense of satisfaction with one's own health and patient's perception of having good access to health-care services. Adherence was inversely proportional to virological

  18. Expression of proposed implantation marker genes CDX2 and HOXB7 in the blastocyst does not distinguish viable from non-viable human embryos

    DEFF Research Database (Denmark)

    Kirkegaard, Kirstine; Hindkjær, Johnny Juhl; Ingerslev, Hans Jakob

    2012-01-01

    expression differs between viable and non-viable embryos in both human and non-humans, suggesting transcriptome analysis of trophectoderm (TE) as a novel method of improving embryo selection. Potential candidate marker genes have been identified with array studies on animal blastocysts. The aim of this study...... was to investigate the expression of selected genes in human blastocysts in relation to the outcome of implantation. Materials and methods: Embryos from 10 oatients undergoing in vitro fertilization treatment were included in the project. A single blastocyst was chosen for biopsy on the morning of day 5 after oocyte...... of 15 key genes associated with developmental competence in animals were evaluated in high quality human embryos with monogenic or chromosomal disorders from a pre-implantation genetic disorder program. Triplicate cDNA amplifications for quantitative (q) RT-PCR were performed using pre-designed gene...

  19. First-Line Cetuximab Monotherapy in KRAS/NRAS/BRAF Mutation-Negative Colorectal Cancer Patients.

    Science.gov (United States)

    Moiseyenko, Vladimir M; Moiseyenko, Fedor V; Yanus, Grigoriy A; Kuligina, Ekatherina Sh; Sokolenko, Anna P; Bizin, Ilya V; Kudriavtsev, Alexey A; Aleksakhina, Svetlana N; Volkov, Nikita M; Chubenko, Vyacheslav A; Kozyreva, Kseniya S; Kramchaninov, Mikhail M; Zhuravlev, Alexandr S; Shelekhova, Kseniya V; Pashkov, Denis V; Ivantsov, Alexandr O; Venina, Aigul R; Sokolova, Tatyana N; Preobrazhenskaya, Elena V; Mitiushkina, Natalia V; Togo, Alexandr V; Iyevleva, Aglaya G; Imyanitov, Evgeny N

    2018-06-01

    Colorectal carcinomas (CRCs) are sensitive to treatment by anti-epidermal growth factor receptor (EGFR) antibodies only if they do not carry activating mutations in down-stream EGFR targets (KRAS/NRAS/BRAF). Most clinical trials for chemo-naive CRC patients involved combination of targeted agents and chemotherapy, while single-agent cetuximab or panitumumab studies included either heavily pretreated patients or subjects who were not selected on the basis of molecular tests. We hypothesized that anti-EGFR therapy would have significant efficacy in chemo-naive patients with KRAS/NRAS/BRAF mutation-negative CRC. Nineteen patients were prospectively included in the study. Two (11%) patients experienced partial response (PR) and 11 (58%) subjects showed stable disease (SD). Median time to progression approached 6.1 months (range 1.6-15.0 months). Cetuximab efficacy did not correlate with RNA expression of EGFR and insulin-like growth factor 2 (IGF2). Only one tumor carried PIK3CA mutation, and this CRC responded to cetuximab. Exome analysis of patients with progressive disease (PD) revealed 1 CRC with high-level microsatellite instability and 1 instance of HER2 oncogene amplification; 3 of 4 remaining patients with PD had allergic reactions to cetuximab, while none of the subjects with PR or SD had this complication. Comparison with 19 retrospective KRAS/NRAS/BRAF mutation-negative patients receiving first-line fluoropyrimidines revealed no advantages or disadvantages of cetuximab therapy. Cetuximab demonstrates only modest efficacy when given as a first-line monotherapy to KRAS/NRAS/BRAF mutation-negative CRC patients. It is of question, why meticulous patient selection, which was undertaken in the current study, did not result in the improvement of outcomes of single-agent cetuximab treatment.

  20. 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.

  1. Vinorelbine as first-line or second-line therapy for advanced breast cancer

    DEFF Research Database (Denmark)

    Langkjer, Sven T; Ejlertsen, Bent; Mouridsen, Henning

    2008-01-01

    INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

  2. THE PHOTOMETRIC AND KINEMATIC STRUCTURE OF FACE-ON DISK GALAXIES. II. INTEGRATED LINE PROFILE CHARACTERIZATION AND THE ORIGIN OF LINE PROFILE ASYMMETRY

    International Nuclear Information System (INIS)

    Andersen, David R.; Bershady, Matthew A.

    2009-01-01

    We perform a moments analysis of H I and H II global line profiles for 33 nearly face-on disk galaxies for the threefold purpose of rationalizing and interpreting line profile indices in the literature, presenting robust moment definitions with analytic error functions calibrated against Monte Carlo simulation, and probing the physical origin of line profile asymmetries. The first four profile moments serve as viable surrogates for the recession velocity, line width, asymmetry, and profile shape, respectively. The first three moments are superior, by a factor of ∼2 in precision, to related quantities defined in the literature. First and third profile moments are related; skew can be used to calculate more accurate recession velocities from global profiles. Second and fourth profile moments are linked, corresponding to the known trend that narrow (but well resolved) line widths tend to be more Gaussian. Hα kurtosis also appears correlated with the spatially resolved line width of the ionized gas. No systematics appear between various measures of line width and true rotation speed other than the wide range of normalizations, which we calibrate. This conclusion and calibration, however, is highly sample dependent. The ratio of H II to H I widths is consistent with unity, even at low projected line width. There may be a trend toward a decrease in the ratio of H II to H I widths consistent with previous studies, but we also observe greater scatter. While there is good agreement between H I and H II first, second, and fourth moments, we find no positive correlation between skew measured from H I and H II profiles. Detailed analysis of the spatially resolved Hα distribution demonstrates that H II global profile asymmetries are dominated by differences in the gas distribution, not kinematic asymmetries.

  3. PMA-PhyloChip DNA Microarray to Elucidate Viable Microbial Community Structure

    Science.gov (United States)

    Venkateswaran, Kasthuri J.; Stam, Christina N.; Andersen, Gary L.; DeSantis, Todd

    2011-01-01

    in the dark. Thereafter, the sample is exposed to visible light for five minutes, so that the DNA from dead cells will be cross-linked. Following this PMA treatment step, the sample is concentrated by centrifugation and washed (to remove excessive PMA) before DNA is extracted. The 16S rRNA gene fragments will be amplified by PCR to screen the total microbial community using PhyloChip DNA microarray analysis. This approach will detect only the viable microbial community since the PMA intercalated DNA from dead cells would be unavailable for PCR amplification. The total detection time including PCR reaction for low biomass samples will be a few hours. Numerous markets may use this technology. The food industry uses spore detection to validate new alternative food processing technologies, sterility, and quality. Pharmaceutical and medical equipment companies also detect spores as a marker for sterility. This system can be used for validating sterilization processes, water treatment systems, and in various public health and homeland security applications.

  4. SOLUTIONS TO OVERCOME BARRIERS TO IMPLEMENTATION OF TREATMENT TECHNOLOGIES

    Science.gov (United States)

    To make treatment a viable option for remediation you must first identify the barriers to implementing treatment. The primary barrier is economics. Treatment options are relatively expensive and there is a lack of funds for treatment. The cost of technologies can be lowered by 1)...

  5. [Clinical observation of icotinib hydrochloride in first-line therapy for pulmonary adenocarcinoma].

    Science.gov (United States)

    Yang, Xinjie; Zhang, Hui; Qin, Na; Li, Xi; Nong, Jingying; Lv, Jialin; Wu, Yuhua; Zhang, Quan; Zhang, Shucai

    2013-07-01

    It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Among the 56 patients, the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4% (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (Picotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

  6. Dasatinib first-line: Multicentric Italian experience outside clinical trials.

    Science.gov (United States)

    Breccia, Massimo; Stagno, Fabio; Luciano, Luigiana; Abruzzese, Elisabetta; Annunziata, Mario; D'Adda, Mariella; Maggi, Alessandro; Sgherza, Nicola; Russo-Rossi, Antonella; Pregno, Patrizia; Castagnetti, Fausto; Iurlo, Alessandra; Latagliata, Roberto; Cedrone, Michele; Di Renzo, Nicola; Sorà, Federica; Rege-Cambrin, Giovanna; La Nasa, Giorgio; Scortechini, Anna Rita; Greco, Giovanna; Franceschini, Luca; Sica, Simona; Bocchia, Monica; Crugnola, Monica; Orlandi, Esther; Guarini, Attilio; Specchia, Giorgina; Rosti, Gianantonio; Saglio, Giuseppe; Alimena, Giuliana

    2016-01-01

    Dasatinib was approved for the treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients in first line therapy based on the demonstration of efficacy and safety reported in patients enrolled in clinical trials. We describe a multicentric Italian "real-life" experience of dasatinib used as frontline treatment outside clinical trials. One hundred and nine patients (median age 54 years) were treated from January 2012 to December 2013. Increased incidence of high risk patients were detected according to stratification (26% according to Sokal score, 19% according to Euro score and 16% according to EUTOS) when compared to company sponsored studies. Median time from diagnosis to start of dasatinib was 18 days. Ten patients received unscheduled starting dose (6 patients 50mg and 4 patients 80 mg QD), whereas 99 patients started with 100mg QD. At 3 months, 92% of patients achieved a BCR-ABL ratio less than 10%. At 6 months, the rate of CCyR was 91% and the rate of MR3 was 40%, with 8% of the patients reaching MR4.5. Ninety-three patients were evaluable at 12 months: the rate of MR3 was 62%, with MR4.5 being achieved by 19% of the patients. At a median follow-up of 12 months, 27 patients (24.7%) were receiving the drug at reduced dose. Two patients (1.8%) experienced a lymphoid blast crisis and the overall incidence of resistance was 8%. As regards safety, the major side effects recorded were thrombocytopenia, neutropenia and pleural effusions, which occurred in 22%, 10% and 8% of patients, respectively. Present results, achieved in a large cohort of patients treated outside clinical trials, further confirm the efficacy and safety of dasatinib as firstline treatment in CML. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Commissioning of the first Manicouagan--Montreal 735 line

    Energy Technology Data Exchange (ETDEWEB)

    Baril, G A; Cahill, K; Dupont, A; Roberge, G

    1966-01-01

    In order to meet increasing demand, Hydro-Quebec will develop seven hydro power sites on the Manicouagan and Outardes Rivers to generate a total of 5,700 MW and an additional 30 billion kWh by 1973. On August 22, 1962, it was decided that the power would be transmitted over a 650-km network, using three 735-kV lines and six stations. The wet switching surge withstand level was set at 1,350 kV, based on the results obtained with a transient network analyser. The main 735-kV equipment was purchased from several manufacturers to insure prompt delivery and continuity of service. On September 21st, 1965, the Manicouagan-Levis section of the first line was energized at 735 kV, transmitting 300 MW. A month later, the second section of the line was energized and the power generated at the Manicouagan 2 plant was thus transmitted to Montreal. So far, only two pieces of equipment have shown signs of failure without causing, however, any serious shutdown. Results of tests carried out show that operation of a 735-kV network is safe and economical.

  8. Lodging resistant pea line derived after mutagenic treatment

    International Nuclear Information System (INIS)

    Naidenova, N.; Vassilevska-Ivanova, R.

    2006-01-01

    Line 1/502 is a new lodging resistant pea ( Pisum sativum L.) developed for the Bulgarian field pea industry. This line is a direct chlorophyll mutant, which originates after treatment of the initial line, cultivar Auralia, with 150 Gy 60 Co γ - radiation. In regional evaluation trials conducted in Sofia over seven successive seasons 1/502 has revealed improved standing ability that most probably is a result from modification of the architecture of the plants appearing in reduction of plant height. The agronomic and morphological characteristics of the mutant line were reported. The upright plant habit and resistance to lodging is especially beneficial for production of high quality peas because pods are held above the soil surface during crop development and during maturity which aids in keeping the peas clean and free of pathogens that can cause discoloration and rotting. (authors)

  9. 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.

  10. Cost-effectiveness analysis of entecavir versus lamivudine in the first-line treatment of Australian patients with chronic hepatitis B.

    Science.gov (United States)

    Arnold, Elizabeth; Yuan, Yong; Iloeje, Uchenna; Cook, Greg

    2008-01-01

    Chronic hepatitis B (CHB) virus infection is a major global healthcare problem. The recent introduction of entecavir in Australia for the treatment of CHB patients in the naive treatment setting has triggered significant optimism with regards to improved clinical outcomes for CHB patients. To estimate, from an Australian healthcare perspective, the cost effectiveness of entecavir 0.5 mg/day versus lamivudine 100 mg/day in the treatment of CHB patients naive to nucleos(t)ide therapy. A cost-utility analysis to project the clinical and economic outcomes associated with CHB disease and treatment was conducted by developing two decision-tree models specific to hepatitis B e antigen-positive (HBeAg+ve) and HBeAg-ve CHB patient subsets. This analysis was constructed using the Australian payer perspective of direct costs and outcomes, with indirect medical costs and lost productivity not being included. The study population comprised a hypothetical cohort of 1000 antiviral treatment-naive CHB patients who received either entecavir 0.5 mg/day or lamivudine 100 mg/day at model entry. The population of patients used in this analysis was representative of those patients likely to receive initial antiviral therapy in clinical practice in Australia. The long-term cost effectiveness of entecavir compared with lamivudine in the first-line treatment of CHB patients was expressed as an incremental cost per life-year gained (LYG) or QALY gained. Results revealed that the availability of entecavir 0.5 mg/day as part of the Australian hepatologist's treatment armamentarium should result in significantly lower future rates of compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC) events (i.e. 54 fewer cases of CC, seven fewer cases of DC, and 20 fewer cases of HCC over the model's timeframe for HBeAg+ve CHB patients, and 69 fewer cases of CC, eight fewer cases of DC and 25 fewer cases of HCC over the model's timeframe for HBeAg-ve CHB patients

  11. Bariatric surgery: a viable treatment option for patients with severe mental illness.

    Science.gov (United States)

    Shelby, Sarah R; Labott, Susan; Stout, Rebecca A

    2015-01-01

    Although bariatric surgery has become a recognized treatment for obesity, its utility among patients with severe psychiatric disorders has not been extensively studied. A few studies have reported similar weight loss outcomes in these patients, but psychiatric status after bariatric surgery has been studied only minimally, and it is unknown if exacerbation of the mental illness affects weight loss. The aim of this study was to shed greater light on the issue of serious mental illness and bariatric surgery. Specifically, do patients with a diagnosis of schizophrenia, bipolar I, and bipolar II have poorer weight loss outcomes postbariatric surgery than the general bariatric surgery population? Also, do patients with these diagnoses experience an exacerbation of psychiatric symptoms after bariatric surgery, and if so, is the exacerbation of these disorders linked to poorer weight loss results? Midwest university medical center. A medical record review of approximately 1500 bariatric patients in a Midwest university medical center was conducted to identify those patients with diagnoses of schizophrenia, bipolar I, and bipolar II. Information was gathered on bariatric surgery outcomes and changes in psychiatric status postsurgery. Eighteen patients were identified as undergoing bariatric surgery and having a diagnosis of schizophrenia, bipolar I, or bipolar II. Weight loss in this group was significant and comparable to expected outcomes of absolute weight lost, changes in body mass index, and percentage excess weight loss for patients in the typical bariatric population. Postsurgery psychiatric status was known on 10 patients. All 10 patients experienced some exacerbation of psychiatric problems yet weight loss outcomes were still as expected. Bariatric surgery is a viable obesity treatment option for patients with schizophrenia, bipolar I, and bipolar II disorders. Symptom exacerbations occurred postsurgery, although it is not clear if these were due to the surgery or

  12. A retrospective case-cohort study comparing treatment outcomes in abacavir versus stavudine containing first line antiretroviral treatment regimens in children <3yrs old, at a paediatric programme based in Soweto, South Africa

    Science.gov (United States)

    Otwombe, Kennedy; Lazarus, Erica; Liberty, Afaaf; Gray, Glenda E.; Greeff, Oppel B. W.; Violari, Avy

    2017-01-01

    Introduction The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated. Methods This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013. Children on abacavir/stavudine who had initiated ART at age 90% for ABC and d4T were similar too (95% in ABC vs. 86% in d4T, p = 0.10). The proportion of children who died over 12 months was 3.5% in the ABC and 7.9% in the d4T group (p = 0.27). Similarly, the anthropometric measures were comparable. Conclusions It is reassuring that in the short term, in this group of patients, the treatment outcomes were similar. PMID:28686654

  13. 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.

  14. Current status of first-line therapy for elderly patients with proatate cancer in Kyushu and Okinawa areas. A questionnaire study

    International Nuclear Information System (INIS)

    Nishiyama, Kenryu; Nakagawa, Masayuki; Koga, Hirofumi

    2005-01-01

    A survey based on a questionnaire to urologists in Kyushu and Okinawa areas was carried out to assess the current status of first-line therapy for elderly patients with prostate cancer. Ninety-three urologists from 93 institutes answered the questionnaire. Endocrine therapy is widely performed as first-line therapy for elderly patients with prostate cancer. They mostly receive immediate-continuous therapy regardless of their clinical factors. Only 8 (9%) and 7 (8%) institutes have the options of deferred and intermittent therapy, respectively. LH-RH analogue and non-steroidal anti-androgens are commonly used. Chemoendocrine therapy is performed in 33 (35%) institutes for selected patients. Estramustine and 5-fluorouracil (5-FU) derivatives are commonly used as chemotherapeutic agents. Sixty (65%) institutes do not have this modality as a treatment option. Risks arising from the treatment and quality of life (QOL) disturbance are the main reasons for this. Radiation therapy and radical prostatectomy are performed in 53 (57%) and 47 (51%) institutes, respectively, for selected patients with loco-regional disease. However, 22 (24%) institutes do not have these definitive therapies as treatment options. QOL and risks arising from the treatments are the main factors for selecting definitive or non-definitive therapy. In elderly patients with prostate cancer, cancer control is not always the goal of treatment. QOL within a relatively shorter life expectancy is an important factor for decision making in the management of these patients. (authors)

  15. Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

    Science.gov (United States)

    Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

    2016-09-01

    To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

  16. Quality of Life in Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer Using Cabazitaxel or Other Therapies After Previous Docetaxel Chemotherapy: Swiss Observational Treatment Registry.

    Science.gov (United States)

    Stenner, Frank; Rothschild, Sacha I; Betticher, Daniel; Caspar, Clemens; Morant, Rudolf; Popescu, Razvan; Rauch, Daniel; Huber, Urs; Zenhäusern, Reinhard; Rentsch, Cyrill; Cathomas, Richard

    2017-08-24

    The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT-P. One hundred thirty-eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT-P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. Some degree of QoL decrease was seen in most patients regardless of second-line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Real-world Direct Health Care Costs for Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab-containing Regimens in First-line or First-line Through Second-line Therapy.

    Science.gov (United States)

    Johnston, Stephen; Wilson, Kathleen; Varker, Helen; Malangone-Monaco, Elisabetta; Juneau, Paul; Riehle, Ellen; Satram-Hoang, Sacha; Sommer, Nicolas; Ogale, Sarika

    2017-12-01

    The present study examined real-world direct health care costs for metastatic colorectal cancer (mCRC) patients initiating first-line (1L) bevacizumab (BEV)- or cetuximab (CET)-containing regimen in 1L or 1L-through-second-line (1L-2L) therapy. Using a large US insurance claims database, patients with mCRC initiating 1L BEV- or 1L CET-containing regimen from January 1, 2008 to September 30, 2014 were identified. The per-patient per-month (PPPM) all-cause health care costs (2014 US dollars) were measured during 1L therapy and, for patients continuing to a 2L biologic-containing regimen, 1L-2L therapy. Multivariable regression analyses were used to compare PPPM total health care costs between patients initiating a 1L BEV- versus 1L CET-containing regimen. A total of 6095 patients initiating a 1L BEV- and 453 initiating a 1L CET-containing regimen were evaluated for 1L costs; 2218 patients initiating a 1L BEV- and 134 initiating a 1L CET-containing regimen were evaluated for 1L-2L costs. In 1L therapy, 1L CET had adjusted PPPM costs that were $3135 (95% confidence interval [CI], $1174-$5040; P < .001) greater on average than 1L BEV. In 1L-2L therapy, 1L BEV-2L CET had adjusted PPPM costs that were $1402 (95% CI, $1365-$1442; P = .010) greater than those for 1L BEV-2L BEV, and 1L CET-2L BEV had adjusted PPPM costs that were $4279 (95% CI, $4167-$4400; P = .001) greater on average than those for 1L BEV-2L BEV. The adjusted PPPM cost differences for 1L BEV-2L other biologic or 1L CET-2L other biologic agent were numerically greater but statistically insignificant. PPPM total health care costs for 1L and 2L therapy tended to be greater for patients treated with 1L CET-containing regimens than for 1L BEV-containing regimens. Also, continuing treatment with BEV-containing regimens 1L-2L was less costly than switching between BEV and CET. The cost differences between BEV and CET hold important implications for treatment decisions of mCRC patients in real-world clinical

  18. [The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

    Science.gov (United States)

    Chen, H; Wang, H P; Zhang, L; Si, X Y

    2017-01-01

    Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

  19. Sensitive and Specific Biomimetic Lipid Coated Microfluidics to Isolate Viable Circulating Tumor Cells and Microemboli for Cancer Detection.

    Directory of Open Access Journals (Sweden)

    Jia-Yang Chen

    Full Text Available Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB "smart coating" to capture viable circulating tumor cells (CTCs and circulating tumor microemboli (CTM directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs.

  20. Managing Viable Knowledge

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.; Vriens, D.J.

    2002-01-01

    In this paper, Beer's Viable System Model (VSM) is applied to knowledge management. Based on the VSM, domains of knowledge are identified that an organization should possess to maintain its viability. The logic of the VSM is also used to support the diagnosis, design and implementation of the

  1. Influence of wellness education on first-line icotinib hydrochloride patients with stage IV non-small cell lung cancer and their family caregivers.

    Science.gov (United States)

    Yanwei, Li; Minghui, Fang; Manman, Quan; Zhuchun, Yan; Dongying, Liu; Zhanyu, Pan

    2018-04-11

    This study aims to examine the effects of wellness education (WE) intervention on the behavioral change, psychological status, performance status on patients with stage IV non-small cell lung cancer (NSCLC) undergoing icotinib hydrochloride treatment and their relationships with family caregivers. We conducted an intervention study involving 126 individuals with confirmed activating epidermal growth factor receptor mutation-positive stage IV NSCLC who received icotinib hydrochloride as first-line therapy between January 2014 and January 2016; their caregivers were also included in the study. For a period of 12 weeks, participants were randomly assigned into WE and control groups. The patients and family members in the WE group were provided with WE information about treatment, diet, social needs, rehabilitation, physical/mental health education, communication strategies, and patient care advice at least 3 times per week during treatment. Qualitative feedback of the participants was recorded during the intervention. Food Composition Database, the Family Environment Scale, patients/caregivers quality-of-life (Functional Assessment of Cancer Therapy-Lung/Caregiver Quality of Life Index-Cancer Scale), and Hospital Anxiety and Depression Scale (HADS) were measured at baseline and for 12 weeks. Data were analyzed to compare the different outcomes. Of the 126 caregivers (64 WE and 62 control), 120 completed the study. We observed significant differences between the WE group and control group with respect to low daily calorie intake (31.0% vs 77.4%, p 0.05). After 12 weeks, WE intervention had improved scores on Functional Assessment of Cancer Therapy-Lung-EWB and Caregiver Quality of Life Index-Cancer Scale adaptation. In addition, the patients also showed improvements in HADS. WE interventions in patients with stage IV NSCLC undergoing icotinib hydrochloride treatment and their family resulted in strong intentions to engage in health-promoting behaviors related to

  2. The Efficacy of Synchronous Combination of Chemotherapy and EGFR TKIs for the First-Line Treatment of NSCLC: A Systematic Analysis.

    Directory of Open Access Journals (Sweden)

    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.

  3. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer

    International Nuclear Information System (INIS)

    Sun, Yan; Cheng, Ying; Hao, Xuezhi; Wang, Jie; Hu, Chengping; Han, Baohui; Liu, Xiaoqing; Zhang, Li; Wan, Huiping; Xia, Zhongjun; Liu, Yunpeng; Li, Wei; Hou, Mei; Zhang, Helong; Xiu, Qingyu; Zhu, Yunzhong; Feng, Jifeng; Qin, Shukui; Luo, Xiaoyan

    2016-01-01

    Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m 2 , day 1) and amrubicin (40 mg/m 2 , days 1–3) once every 21 days. EP-treated patients received cisplatin (80 mg/m 2 , day 1) and etoposide (100 mg/m 2 , days 1–3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal. Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95 % confidence interval for hazard ratio 0.63–1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8 % vs. 57.3 %, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4 %; EP 44.0 %). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable. AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China. This trial was registered on 10 April 2008 (ClinicalTrials.gov: NCT00660504)

  4. Value of 18F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

    International Nuclear Information System (INIS)

    Palard-Novello, X.; Querellou, S.; Abgral, R.; Salauen, P.Y.; Gouillou, M.; Saraux, A.; Devauchelle-Pensec, V.; Marhadour, T.; Garrigues, F.

    2016-01-01

    To evaluate the use of 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.)

  5. Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.

    Science.gov (United States)

    Granito, Alessandro; Marinelli, Sara; Terzi, Eleonora; Piscaglia, Fabio; Renzulli, Matteo; Venerandi, Laura; Benevento, Francesca; Bolondi, Luigi

    2015-06-01

    No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  6. Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997–2010

    Science.gov (United States)

    Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; DiMeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

    2014-01-01

    recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival. PMID:24463354

  7. Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

    Science.gov (United States)

    Zaanan, Aziz; Samalin, Emmanuelle; Aparicio, Thomas; Bouche, Olivier; Laurent-Puig, Pierre; Manfredi, Sylvain; Michel, Pierre; Monterymard, Carole; Moreau, Marie; Rougier, Philippe; Tougeron, David; Taieb, Julien; Louvet, Christophe

    2018-04-01

    In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated. GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity. Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions. The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index. This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432). Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  8. Review of first line supervisory positions in nuclear power plants - Phase II

    Energy Technology Data Exchange (ETDEWEB)

    Mackenzie, C W; Huntley, M [Hickling Corp., Ottawa, ON (Canada)

    1995-10-01

    This report provides an overview of first line supervisory activities at Ontario Hydro nuclear generating stations (Pickering `A` and Bruce `B`) and the Point Lepreau nuclear generating station in New Brunswick. Activity profiles describing the range of first line supervisory roles and responsibilities for nuclear operators have been developed from survey data and flowcharting methods. These activity profiles have then been compared with formal job responsibilities as identified in job descriptions, supervisory training provided and assessment criteria used to evaluate supervisors. Finally, this report relates the findings of supervisory practices in the group under study with the findings in the current literature relating to supervisory functioning. (author). 32 tabs., 2 figs.

  9. Review of first line supervisory positions in nuclear power plants - Phase II

    International Nuclear Information System (INIS)

    Mackenzie, C.W.; Huntley, M.

    1995-10-01

    This report provides an overview of first line supervisory activities at Ontario Hydro nuclear generating stations (Pickering 'A' and Bruce 'B') and the Point Lepreau nuclear generating station in New Brunswick. Activity profiles describing the range of first line supervisory roles and responsibilities for nuclear operators have been developed from survey data and flowcharting methods. These activity profiles have then been compared with formal job responsibilities as identified in job descriptions, supervisory training provided and assessment criteria used to evaluate supervisors. Finally, this report relates the findings of supervisory practices in the group under study with the findings in the current literature relating to supervisory functioning. (author). 32 tabs., 2 figs

  10. 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

  11. Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study.

    Science.gov (United States)

    Turpin, Anthony; Paget-Bailly, Sophie; Ploquin, Anne; Hollebecque, Antoine; Peugniez, Charlotte; El-Hajbi, Farid; Bonnetain, Franck; Hebbar, Mohamed

    2018-03-01

    We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab. We assessed OS, progression-free survival (PFS), duration of disease control (DDC), the sum of the periods in which the disease did not progress, and the time to failure of strategy (TFS), which was defined as the entire period before the introduction of a second-line treatment. Linear correlation and regression models were used, and Prentice criteria were investigated. With a median follow-up of 57.6 months for 216 patients, the median OS was 24.5 months (95% confidence interval [CI], 21.3-29.7). The median PFS, DDC, and TFS were 8.9 (95% CI, 8.4-9.7), 11.0 (95% CI, 9.8-12.4), and 11.1 (95% CI, 10.0-13.0) months, respectively. The correlations between OS and DDC (Pearson coefficient, 0.79 [95% CI, 0.73-0.83], determination coefficient, 0.62) and OS and TFS (Pearson coefficient, 0.79 [95% CI, 0.73-0.84], determination coefficient, 0.63) were satisfactory. Linear regression analysis showed a significant association between OS and DDC, and between OS and TFS. Prentice criteria were verified for TFS as well as DDC. DDC and TFS correlated with OS and are relevant as intermediate criteria in the setting of patients with mCRC treated with a first-line bevacizumab-based regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review

    DEFF Research Database (Denmark)

    Benfield, T.; Atzori, C.; Miller, R.F.

    2008-01-01

    BACKGROUND: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). METHODS: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007...... and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs). RESULTS: Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82...... individual cases from the tricenter study, yielded a total of 468 PCP second-line treatment episodes. Response rates to second-line treatment were comparable for trimethoprim-sulfamethoxazole (TMP-SMX; 68%) and clindamycin-primaquine (73%) (OR for response = 2.1 [95% confidence interval (CI): 1.1 to 3...

  13. Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

    2018-01-01

    Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

  14. Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

    Science.gov (United States)

    Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

    2015-06-01

    To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

  15. Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy.

    Science.gov (United States)

    Rier, Hánah N; Jager, Agnes; Sleijfer, Stefan; van Rosmalen, Joost; Kock, Marc C J M; Levin, Mark-David

    2017-02-01

    Low muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT). A skeletal muscle index (SMI) in cm 2 /m 2 and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Fourteen-day high-dose esomeprazole, amoxicillin and metronidazole as third-line treatment for Helicobacter pylori infection.

    Science.gov (United States)

    Puig, Ignasi; González-Santiago, Jesús M; Molina-Infante, Javier; Barrio, Jesús; Herranz, Maria Teresa; Algaba, Alicia; Castro, Manuel; Gisbert, Javier P; Calvet, Xavier

    2017-09-01

    The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole. Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or 13 C-UBT both before and after treatment. A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred. Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens. © 2017 John Wiley & Sons Ltd.

  17. 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.

  18. Studies on chlorophyll and viable mutations in green gram (Vigna radiata L. Wilczek) II: Response to mutagen

    Energy Technology Data Exchange (ETDEWEB)

    Krishnaswami, S; Rathinam, M [Tamil Nadu Agricultural Univ., Coimbatore (India). Dept. of Agricultural Botany

    1980-09-01

    The frequency and spectrum of chlorophyll and viable mutations in relation to type and dose of mutagen and cluster progenies were studied in four green gram cultivars viz., Kopergaon, Pusa Baisakhi, L. 24/2 and Sel. 122 subjected to two levels of EMS and gamma irradiation, severally and in conjunction. While chlorophyll mutations did not vary with the mutagen dose, viable mutations exhibited a direct relationship. Combinations of the mutagens were more effective in mutation induction. While no difference was manifested between the cluster families in respect of chlorophyll mutations, progenies of the second cluster recorded less viable mutations than either the first or the third. Viridis and xanthoviridis among chlorophyll mutations, and those affecting plant duration and stature among viable were more predominant.

  19. Immediate natural tooth pontic: A viable yet temporary prosthetic solution: A patient reported outcome

    Directory of Open Access Journals (Sweden)

    Sudhir Bhandari

    2012-01-01

    Conclusion: The concept of immediate pontic placement is surely a viable treatment option and promises an excellent transient esthetic solution for a lost tooth as well as enables good preparation of the extraction site for future prosthetic replacement.

  20. Does first line antiretroviral therapy increase the prevalence of cardiovascular risk factors in Indian patients?: A cross sectional study.

    Science.gov (United States)

    Carey, R A B; Rupali, P; Abraham, O C; Kattula, D

    2013-01-01

    Antiretroviral therapy (ART) is associated with a myriad of metabolic complications which are potential cardiovascular risk factors. Early detection of these risk factors could help in alleviating morbidity and mortality in human immunodeficiency virus (HIV) infected patients on ART. To study the prevalence of cardiovascular risk factors in patients on a combination of nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) - the standard combination first line ART regimen used in tertiary referral center. The prevalence of cardiovascular risk factors in HIV infected subjects with stage 1t disease on standard first line ART for at least 1 year, HIV infected subjects with stage 1 disease and not on ART and HIV negative subjects was assessed. The study was a cross-sectional study design. Basic demographic data was collected and patients were examined for anthropometric data and blood was collected for analysis of blood glucose, serum lipids, and fasting insulin levels. Chi-square test was used to calculate significance. Statistical Package for Social Sciences (SPSS) software version 16.0 was used for data analysis. The prevalence of hypercholesterolemia and hypertriglyceridemia was higher in the patients on ART when compared to patients not on ART (PART and those not on ART. First line ART is associated with increased prevalence of dyslipidemia. Early detection and treatment of dyslipidemia should help in reducing the cardiovascular morbidity in patients on ART.

  1. Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.

    Science.gov (United States)

    Beck, J Thaddeus; Hortobagyi, Gabriel N; Campone, Mario; Lebrun, Fabienne; Deleu, Ines; Rugo, Hope S; Pistilli, Barbara; Masuda, Norikazu; Hart, Lowell; Melichar, Bohuslav; Dakhil, Shaker; Geberth, Matthias; Nunzi, Martina; Heng, Daniel Y C; Brechenmacher, Thomas; El-Hashimy, Mona; Douma, Shyanne; Ringeisen, Francois; Piccart, Martine

    2014-02-01

    The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.

  2. Power in health care organizations: contemplations from the first-line management perspective.

    Science.gov (United States)

    Isosaari, Ulla

    2011-01-01

    The aim of this paper is to examine health care organizations' power structures from the first-line management perspective. What liable power structures derive from the theoretical bases of bureaucratic, professional and result based organizations, and what power type do health care organizations represent, according to the empirical data? The paper seeks to perform an analysis using Mintzberg's power configurations of instrument, closed system, meritocracy and political arena. The empirical study was executed at the end of 2005 through a survey in ten Finnish hospital districts in both specialized and primary care. Respondents were all first-line managers in the area and a sample of staff members from internal disease, surgical and psychiatric units, as well as out-patient and primary care units. The number of respondents was 1,197 and the response percentage was 38. The data were analyzed statistically. As a result, it can be seen that a certain kind of organization structure supports the generation of a certain power type. A bureaucratic organization generates an instrument or closed system organization, a professional organization generates meritocracy and also political arena, and a result-based organization has a connection to political arena and meritocracy. First line managers regarded health care organizations as instruments when staff regarded them mainly as meritocracies having features of political arena. Managers felt their position to be limited by rules, whereas staff members regarded their position as having lots of space and influence potential. If the organizations seek innovative and active managers at the unit level, they should change the organizational structure and redistribute the work so that there could be more space for meaningful management. This research adds to the literature and gives helpful suggestions that will be of interest to those in the position of first-line management in health care.

  3. Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

    International Nuclear Information System (INIS)

    Farina, Davide; Morassi, Mauro; Maroldi, Roberto; Roca, Elisa; Tassi, Gianfranco; Cavalleri, Giuseppe

    2013-01-01

    To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

  4. Comparison of Efficacy and Safety of Different Therapeutic Regimens as 
Second-line Treatment for Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhihua LI

    2015-05-01

    Full Text Available Background and objective Small-cell lung cancer (SCLC is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress after the first-line therapy. The evidence of a benefit from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the efficacy and safety of different second-line treatment regimens. Methods We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC, and the rest 152 patients received second-line chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. The endpoints were objective response rate (ORR, disease control rate (DCR, progression-free survival (PFS, and overall survival (OS. Results Patients administered second-line chemotherapy lived significantly longer, with a total OS from first-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001, and the ORR, DCR, PFS and OS of the former (including the sensitive disease and resistance/refractory disease patients were obviously better than that of the latter. The ORR and DCR of the patients who received second-line chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second-line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line chemotherapy were divided by types of second-line regimens. The sensitive disease patients were from group A (VP-16-based rechallenge and group B1 (CPT-11-based regimen. The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6% and 58.8%, respectively. There was no statistically significant difference (P=0.264; P=0

  5. Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis

    Directory of Open Access Journals (Sweden)

    Yunzhou Shi

    2013-11-01

    Full Text Available Quantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRIR1 mapping with diffusionbased multispectral (MS analysis is introduced. This approach restricts the partial pressure of oxygen (pO2 measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1 and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980. GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment.

  6. adverse events to first line anti-tuberculosis drugs in patients co

    African Journals Online (AJOL)

    status on the risk of developing adverse events to first line anti-TB therapy. Method: The ... with TB-HIV infection were allocated to a second group. ... and negative responses were entered into individual .... Extra-pulmonary TB (yes versus no).

  7. First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

    Science.gov (United States)

    Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

    2011-01-01

    Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

  8. Influence of heat treatment on physicochemical and rheological characteristics of natural yogurts

    Directory of Open Access Journals (Sweden)

    Juliana Aparecida Célia

    2017-08-01

    Full Text Available The aim of this study was to assess the influence of heat treatment on physicochemical and rheological characteristics of natural yogurts, as well as the influence of lyophilization process on natural yogurts after reconstitution. In the first experiment, three yogurt treatments were processed, as follows: Treatment 1, yogurt produced with raw refrigerated milk; Treatment 2, yogurt produced with refrigerated pasteurized milk; and Treatment 3, yogurt produced with UHT (ultra-high temperature milk, in addition to analyses of fat, protein, moisture, titratable acidity, and pH. The shelf life of yogurts at 1, 8, 15, 22, and 29 days of storage, as well as pH, acidity, syneresis, viscosity, viable lactic bacteria, and total coliforms were also assessed. In the second experiment, yogurts were submitted to lyophilization process, performed by scanning electron microscopy analysis and subsequently in those reconstituted, in addition to being assessed the physicochemical, rheological, and viable lactic bacteria characteristics. The results found in the first experiment showed that heat treatment was positive for viscosity, syneresis, and lactic bacteria, being viable until the 15th day of storage only for yogurts submitted to heat treatment. In the second experiment, lyophilization preserved the physicochemical characteristics of yogurts, but the number of initial lactic bacteria was different, also negatively affecting yogurt viscosity.

  9. First observation of the Λ(1405) line shape in electroproduction

    Science.gov (United States)

    Lu, H. Y.; Schumacher, R. A.; Adhikari, K. P.; Adikaram, D.; Aghasyan, M.; Amaryan, M. J.; Pereira, S. Anefalos; Ball, J.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A. S.; Boiarinov, S.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Chandavar, S.; Cole, P. L.; Collins, P.; Contalbrigo, M.; Cortes, O.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Doughty, D.; Dupre, R.; Egiyan, H.; Alaoui, A. El; Fassi, L. El; Eugenio, P.; Fedotov, G.; Fegan, S.; Fleming, J. A.; Gabrielyan, M.; Gevorgyan, N.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Goetz, J. T.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guo, L.; Hafidi, K.; Hakobyan, H.; Harrison, N.; Heddle, D.; Hicks, K.; Ho, D.; Holtrop, M.; Hyde, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jo, H. S.; Joo, K.; Keller, D.; Khandaker, M.; Kim, W.; Klein, A.; Klein, F. J.; Koirala, S.; Kubarovsky, A.; Kubarovsky, V.; Kuleshov, S. V.; Lewis, S.; Livingston, K.; MacGregor, I. J. D.; Martinez, D.; Mayer, M.; McKinnon, B.; Meyer, C. A.; Mineeva, T.; Mirazita, M.; Mokeev, V.; Montgomery, R. A.; Moriya, K.; Moutarde, H.; Munevar, E.; Camacho, C. Munoz; Nadel-Turonski, P.; Nepali, C. S.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Pappalardo, L. L.; Paremuzyan, R.; Park, K.; Park, S.; Pasyuk, E.; Peng, P.; Phelps, E.; Phillips, J. J.; Pisano, S.; Pogorelko, O.; Pozdniakov, S.; Price, J. W.; Procureur, S.; Prok, Y.; Protopopescu, D.; Puckett, A. J. R.; Raue, B. A.; Rimal, D.; Ripani, M.; Rosner, G.; Rossi, P.; Sabatié, F.; Saini, M. S.; Salgado, C.; Schott, D.; Seder, E.; Seraydaryan, H.; Sharabian, Y. G.; Smith, G. D.; Sober, D. I.; Sokhan, D.; Stepanyan, S. S.; Stoler, P.; Strauch, S.; Taiuti, M.; Tang, W.; Tian, Ye; Tkachenko, S.; Torayev, B.; Vernarsky, B.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Weygand, D. P.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhang, J.; Zhao, Z. W.

    2013-10-01

    We report the first observation of the line shape of the Λ(1405) from electroproduction, and show that it is not a simple Breit-Wigner resonance. Electroproduction of K+Λ(1405) off the proton was studied by using data from CLAS at Jefferson Lab in the range 1.0line shape. In our fits, the line shape corresponds approximately to predictions of a two-pole meson-baryon picture of the Λ(1405), with a lower mass pole near 1368 MeV/c2 and a higher mass pole near 1423 MeV/c2. Furthermore, with increasing photon virtuality the mass distribution shifts toward the higher mass pole.

  10. In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines

    International Nuclear Information System (INIS)

    Lautenschlaeger, Tim; Perry, James; Peereboom, David; Li, Bin; Ibrahim, Ahmed; Huebner, Alexander; Meng, Wei; White, Julia; Chakravarti, Arnab

    2013-01-01

    Brain metastasis from breast cancer poses a major clinical challenge. Integrins play a role in regulating adhesion, growth, motility, and survival, and have been shown to be critical for metastatic growth in the brain in preclinical models. Cilengitide, an αvβ3/αvβ5 integrin inhibitor, has previously been studied as an anti-cancer drug in various tumor types. Previous studies have shown additive effects of cilengitide and radiation in lung cancer and glioblastoma cell lines. The ability of cilengitide to enhance the effects of radiation was examined preclinically in the setting of breast cancer to assess its possible efficacy in the setting of brain metastasis from breast cancer. Our panel of breast cells was composed of four cell lines: T-47D (ER/PR+, Her2-, luminal A), MCF-7 (ER/PR+, Her2-, luminal A), MDA-MB-231 (TNBC, basal B), MDA-MB-468 (TNBC, basal A). The presence of cilengitide targets, β3 and β5 integrin, was first determined. Cell detachment was determined by cell counting, cell proliferation was determined by MTS proliferation assay, and apoptosis was measured by Annexin V staining and flow cytometry. The efficacy of cilengitide treatment alone was analyzed, followed by assessment of combined cilengitide and radiation treatment. Integrin β3 knockdown was performed, followed by cilengitide and radiation treatment to test for incomplete target inhibition by cilengitide, in high β3 expressing cells. We observed that all cell lines examined expressed both β3 and β5 integrin and that cilengitide was able to induce cell detachment and reduced proliferation in our panel. Annexin V assays revealed that a portion of these effects was due to cilengitide-induced apoptosis. Combined treatment with cilengitide and radiation served to further reduce proliferation compared to either treatment alone. Following β3 integrin knockdown, radiosensitization in combination with cilengitide was observed in a previously non-responsive cell line (MDA-MB-231

  11. Enumeration of viable and non-viable larvated Ascaris eggs with quantitative PCR

    Science.gov (United States)

    Aims: The goal of the study was to further develop an incubation-qPCR method for quantifying viable Ascaris eggs. The specific objectives were to characterize the detection limit and number of template copies per egg, determine the specificity of the method, and test the method w...

  12. Efficacy of ablation at the anteroseptal line for the treatment of perimitral flutter

    Directory of Open Access Journals (Sweden)

    Bernard Abi-Saleh, MD, FACP, FACC, FHRS

    2015-12-01

    Conclusion: Ablation at the left atrial anteroseptal line is safe and efficacious for the treatment of PMF. Unlike ablation at the traditional mitral isthmus line, ablation at the left atrial anteroseptal line does not require ablation in the coronary sinus.

  13. Systematic review, meta-analysis, and meta-regression: Successful second-line treatment for Helicobacter pylori.

    Science.gov (United States)

    Muñoz, Neus; Sánchez-Delgado, Jordi; Baylina, Mireia; Puig, Ignasi; López-Góngora, Sheila; Suarez, David; Calvet, Xavier

    2018-06-01

    Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates. A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software. The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates. Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates. © 2018 John Wiley & Sons Ltd.

  14. Cigarette smoking habit does not reduce the benefit from first line trastuzumab-based treatment in advanced breast cancer patients.

    Science.gov (United States)

    Santini, Daniele; Vincenzi, Bruno; Adamo, Vincenzo; Addeo, Raffaele; Fusco, Vittorio; Russo, Antonio; Montemurro, Filippo; Roato, Ilaria; Redana, Stefania; Lanzetta, Gaetano; Satolli, Maria Antonietta; Berruti, Alfredo; Leoni, Valentina; Galluzzo, Sara; Antimi, Mauro; Ferraro, Giuseppa; Rossi, Maura; Del Prete, Salvatore; Valerio, Maria Rosaria; Marra, Monica; Caraglia, Michele; Tonini, Giuseppe

    2011-06-01

    Many ErbB2-positive cancers may show intrinsic resistance, and the frequent development of acquired resistance to ErbB-targeted agents represents a substantial clinical problem. The constitutive NF-κB activation in some HER-2/neu positive breast cancer may represent a potential cause of resistance to trastuzumab therapy. Preclinical data revealed that 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine is able to enhance NF-κB DNA binding activity and theoretically to increase the resistance to trastuzumab. Two hundred and forty-eight women with pathologically confirmed, uni- or bidimensionally measurable, HER-2-positive metastatic breast cancer (MBC) treated with trastuzumab-based therapy as first line combination for metastatic disease were considered eligible. For all included patients data on smoking habit were detectable from medical records. We retrospectively analysed the smoking habits of 248 MBC patients and correlated these habits with activity and efficacy of trastuzumab-based therapy. No statistically significant difference in terms of response rate (RR), time to progression (TTP) and overall survival (OS) was identified between smokers (former plus active smokers) and never smokers. Moreover, no statistically significant difference in terms of RR, TTP and OS was identified either comparing active smokers and former smokers. Moreover, we did not observed any significant statistical difference in terms of TTP and OS between smokers ≥10 cigarettes/day and smoking habit and both activity and efficacy of trastuzumab-based first line therapy in metastatic HER2/neu positive breast cancer patients.

  15. 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.)

  16. Stent therapy for malignant superior vena cava syndrome: Should be first line therapy or simple adjunct to radiotherapy

    International Nuclear Information System (INIS)

    Chatziioannou, A.; Alexopoulos, Th.; Mourikis, D.; Dardoufas, K.; Katsenis, K.; Lazarou, S.; Koutoulidis, V.; Ladopoulos, Ch.; Vlachos, L.

    2003-01-01

    The goal of this paper is to present our experience with superior vena cava (SVC) stenting, as first line procedure for immediate relief, in patients with malignancy, and its potential influence in the subsequent radiotherapy (XRT). Over a 1-year period, 18 patients with SVC syndrome due to severe stenosis secondary to mediastinal malignancy were referred for stent insertion. A SVC score was used to measure treatment effectiveness. Stent insertion had been successful in 18/18 patients (technical success 100%). All patients experienced symptomatic relief within few hours of the procedure. There were no major complications. In all patients we were able to start radiotherapy (XRT) the next day, after stenting according to our new institutional protocol. All patients were able to comply with the XRT program, perfectly well. Conclusions: SVC stenting provides immediate significant relief of the very annoying SVC syndrome symptoms, thus facilitating excellent compliance of all the patients to the subsequently XRT protocols. We strongly recommend SVC stenting as first line procedure, in patients with SVC syndrome due to malignancy prior to radiotherapy

  17. First-line endoscopic treatment with over-the-scope clips significantly improves the primary failure and rebleeding rates in high-risk gastrointestinal bleeding: A single-center experience with 100 cases.

    Science.gov (United States)

    Richter-Schrag, Hans-Jürgen; Glatz, Torben; Walker, Christine; Fischer, Andreas; Thimme, Robert

    2016-11-07

    To evaluate rebleeding, primary failure (PF) and mortality of patients in whom over-the-scope clips (OTSCs) were used as first-line and second-line endoscopic treatment (FLET, SLET) of upper and lower gastrointestinal bleeding (UGIB, LGIB). A retrospective analysis of a prospectively collected database identified all patients with UGIB and LGIB in a tertiary endoscopic referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016 ( n = 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores were calculated from patients with UGIB. The scores were categorized as < or ≥ 7 and were compared with the original Rockall data. Differences between FLET and SLET were calculated. Univariate and multivariate analysis were performed to evaluate the factors that influenced rebleeding after OTSC placement. Primary hemostasis and clinical success of bleeding lesions (without rebleeding) was achieved in 88/100 (88%) and 78/100 (78%), respectively. PF was significantly lower when OTSCs were applied as FLET compared to SLET (4.9% vs 23%, P = 0.008). In multivariate analysis, patients who had OTSC placement as SLET had a significantly higher rebleeding risk compared to those who had FLET (OR 5.3; P = 0.008). Patients with Rockall risk scores ≥ 7 had a significantly higher in-hospital mortality compared to those with scores < 7 (35% vs 10%, P = 0.034). No significant differences were observed in patients with scores < or ≥ 7 in rebleeding and rebleeding-associated mortality. Our data show for the first time that FLET with OTSC might be the best predictor to successfully prevent rebleeding of gastrointestinal bleeding compared to SLET. The type of treatment determines the success of primary hemostasis or primary failure.

  18. PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.

    Science.gov (United States)

    Wu, Kai-Jie; Pei, Xin-Qi; Tian, Ge; Wu, Da-Peng; Fan, Jin-Hai; Jiang, Yu-Mei; He, Da-Lin

    2018-01-01

    Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

  19. Slim by design: serving healthy foods first in buffet lines improves overall meal selection.

    Directory of Open Access Journals (Sweden)

    Brian Wansink

    Full Text Available OBJECTIVE: Each day, tens of millions of restaurant goers, conference attendees, college students, military personnel, and school children serve themselves at buffets--many being all-you-can-eat buffets. Knowing how the food order at a buffet triggers what a person selects could be useful in guiding diners to make healthier selections. METHOD: The breakfast food selections of 124 health conference attendees were tallied at two separate seven-item buffet lines (which included cheesy eggs, potatoes, bacon, cinnamon rolls, low-fat granola, low-fat yogurt, and fruit. The food order between the two lines was reversed (least healthy to most healthy, and vise-versa. Participants were randomly assigned to choose their meal from one line or the other, and researchers recorded what participants selected. RESULTS: With buffet foods, the first ones seen are the ones most selected. Over 75% of diners selected the first food they saw, and the first three foods a person encountered in the buffet comprised 66% of all the foods they took. Serving the less healthy foods first led diners to take 31% more total food items (p<0.001. Indeed, diners in this line more frequently chose less healthy foods in combinations, such as cheesy eggs and bacon (r = 0.47; p<0.001 or cheesy eggs and fried potatoes (r= 0.37; p<0.001. This co-selection of healthier foods was less common. CONCLUSIONS: Three words summarize these results: First foods most. What ends up on a buffet diner's plate is dramatically determined by the presentation order of food. Rearranging food order from healthiest to least healthy can nudge unknowing or even resistant diners toward a healthier meal, helping make them slim by design. Health-conscious diners, can proactively start at the healthier end of the line, and this same basic principle of "first foods most" may be relevant in other contexts - such as when serving or passing food at family dinners.

  20. Slim by design: serving healthy foods first in buffet lines improves overall meal selection.

    Science.gov (United States)

    Wansink, Brian; Hanks, Andrew S

    2013-01-01

    Each day, tens of millions of restaurant goers, conference attendees, college students, military personnel, and school children serve themselves at buffets--many being all-you-can-eat buffets. Knowing how the food order at a buffet triggers what a person selects could be useful in guiding diners to make healthier selections. The breakfast food selections of 124 health conference attendees were tallied at two separate seven-item buffet lines (which included cheesy eggs, potatoes, bacon, cinnamon rolls, low-fat granola, low-fat yogurt, and fruit). The food order between the two lines was reversed (least healthy to most healthy, and vise-versa). Participants were randomly assigned to choose their meal from one line or the other, and researchers recorded what participants selected. With buffet foods, the first ones seen are the ones most selected. Over 75% of diners selected the first food they saw, and the first three foods a person encountered in the buffet comprised 66% of all the foods they took. Serving the less healthy foods first led diners to take 31% more total food items (pselection of healthier foods was less common. Three words summarize these results: First foods most. What ends up on a buffet diner's plate is dramatically determined by the presentation order of food. Rearranging food order from healthiest to least healthy can nudge unknowing or even resistant diners toward a healthier meal, helping make them slim by design. Health-conscious diners, can proactively start at the healthier end of the line, and this same basic principle of "first foods most" may be relevant in other contexts - such as when serving or passing food at family dinners.

  1. 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

  2. Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study.

    Science.gov (United States)

    Bares, R; Khalid, N; Daniel, H; Dittmann, H; Reimold, M; Gallwitz, B; Schmotzer, C

    2016-07-01

    Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.

  3. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Mezei Z

    2012-10-01

    Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

  4. 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.

  5. Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

    Science.gov (United States)

    Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

    2015-01-01

    Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

  6. HDAC gene expression in pancreatic tumor cell lines following treatment with the HDAC inhibitors panobinostat (LBH589) and trichostatine (TSA).

    Science.gov (United States)

    Mehdi, Ouaïssi; Françoise, Silvy; Sofia, Costa Lima; Urs, Giger; Kevin, Zemmour; Bernard, Sastre; Igor, Sielezneff; Anabela, Cordeiro-da-Silva; Dominique, Lombardo; Eric, Mas; Ali, Ouaïssi

    2012-01-01

    In this study, the effect of LBH589 and trichostatin (TSA), a standard histone deacetylase inhibitor (HDACi) toward the growth of pancreatic cancer cell lines was studied. Thus, we examined for the first time, the HDAC family gene expression levels before and after drug treatment. Several human pancreatic cancer cell lines (Panc-1, BxPC-3, SOJ-6) and a normal human pancreatic duct immortalized epithelial cell line (HPDE/E6E7) were used as target cells. The cell growth was measured by MTT assay, cell cycle alteration, membrane phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane potential loss, RT-PCR and Western blots were done using standard methods. The effect of drugs on tumor growth in vivo was studied using subcutaneous xenograft model. Except in the case of certain HDAC gene/tumor cell line couples: (SIRT1/HPDE-SOJ6/TSA- or LBH589-treated cells; LBH589-treated Panc-1 Cells; HDAC2/BxPC-3/LBH589-treated cells or TSA-treated SOJ-6-1 cells), there were no major significant changes of HDACs genes transcription in cells upon drug treatment. However, significant variation in HDACs and SIRTs protein expression levels could be seen among individual cell samples. The in vivo results showed that LBH589 formulation exhibited similar tumor reduction efficacy as the commercial drug gemcitabine. Our data demonstrate that LBH589 induced the death of pancreatic tumor cell by apoptosis. In line with its in vitro activity, LBH589 achieved a significant reduction in tumor growth in BxPC-3 pancreatic tumor cell line subcutaneous xenograft mouse model. Furthermore, exploring the impact of LBH589 on HDACs encoding genes expression revealed for the first time that some of them, depending on the cell line considered, seem to be regulated during translation. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  7. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report

    Directory of Open Access Journals (Sweden)

    María Espinosa Bosch

    2016-07-01

    Full Text Available Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5–12.6] vs. 7.9 months [6.7–9.1]; HR 0.75 [95% CI 0.60–0.92], p=0.0073. The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER per year of life with PFS in the overall population of 134,274.47 € (notified price. In the adenocarcinoma population per each life of year gained (LYG, the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and

  8. The ghost of extinction: Preservation values and minimum viable population in wildlife models

    NARCIS (Netherlands)

    Eiswerth, M.E.; Kooten, van G.C.

    2009-01-01

    The inclusion of a minimum viable population in bioeconomic modeling creates at least two complications that are not resolved by using a modified logistic growth function. The first complication can be dealt with by choosing a different depensational growth function. The second complication relates

  9. Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

    Science.gov (United States)

    Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

    2012-04-01

    We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

  10. Expert System Development on On-line Measurement of Sewage Treatment Based Process

    Directory of Open Access Journals (Sweden)

    Jianjun QIN

    2014-02-01

    Full Text Available This article puts forward a solution in which an instrument on-line automatic measurement and expert system process are optimized according to the complexity and great process dynamics of sewage treatment process. Firstly modeling has been set up with configuration sewage treatment process in which the process has been integrated into the computer software environment. Secondly certain number of water quality automatic monitoring instruments and sensor probes are set in the reaction tanks according to the needs of process changes and management. The data information acquired can be displayed and recorded at the real time. A human-machine integration expert system featuring computer automation management is developed for the base by one-off method thus to realize the intelligent and unmanned management. The advantages brought about from it can fill up the inexperience of the on-site management personnel and solve the contradiction between the water quality dynamics and difficulty in the process adjustment.

  11. Membrane Lipids as Indicators for Viable Bacterial Communities Inhabiting Petroleum Systems.

    Science.gov (United States)

    Gruner, Andrea; Mangelsdorf, Kai; Vieth-Hillebrand, Andrea; Horsfield, Brian; van der Kraan, Geert M; Köhler, Thomas; Janka, Christoph; Morris, Brandon E L; Wilkes, Heinz

    2017-08-01

    Microbial activity in petroleum reservoirs has been implicated in a suite of detrimental effects including deterioration of petroleum quality, increases in oil sulfur content, biofouling of steel pipelines and other infrastructures, and well plugging. Here, we present a biogeochemical approach, using phospholipid fatty acids (PLFAs), for detecting viable bacteria in petroleum systems. Variations within the bacterial community along water flow paths (producing well, topside facilities, and injection well) can be elucidated in the field using the same technique, as shown here within oil production plants in the Molasse Basin of Upper Austria. The abundance of PLFAs is compared to total cellular numbers, as detected by qPCR of the 16S rDNA gene, to give an overall comparison between the resolutions of both methods in a true field setting. Additionally, the influence of biocide applications on lipid- and DNA-based quantification was investigated. The first oil field, Trattnach, showed significant PLFA abundances and cell numbers within the reservoir and topside facilities. In contrast, the second field (Engenfeld) showed very low PLFA levels overall, likely due to continuous treatment of the topside facilities with a glutaraldehyde-based antimicrobial. In comparison, Trattnach is dosed once per week in a batch fashion. Changes within PLFA compositions across the flow path, throughout the petroleum production plants, point to cellular adaptation within the system and may be linked to shifts in the dominance of certain bacterial types in oil reservoirs versus topside facilities. Overall, PLFA-based monitoring provides a useful tool to assess the abundance and high-level taxonomic diversity of viable microbial populations in oil production wells, topside infrastructure, pipelines, and other related facilities.

  12. Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Bazarbashi, Shouki; Aljubran, Ali; Alzahrani, Ahmad; Mohieldin, Ahmed; Soudy, Hussein; Shoukri, Mohammed

    2015-01-01

    Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m 2 . Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity

  13. 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

    Researchers advocate that interventions should apply a participatory approach i.e. employee participation. It is also widely recognized that top management’s support is an important part of a successful intervention implementation. Lately there has been a request for multi-level intervention...... momentum and increase chances of successful implementation. Four SMEs participated in the study. The typical intervention construct was that top management initiated the intervention and first line managers had to manage the intervention on a daily basis together with two selected employees who acted as in...... between top management and first line management. The top manager’s most important responsibilities were to ensure that the first line manager understood the purpose of the intervention, and to support the first line manager’s dispositions through the intervention. The first line manager’s most important...

  14. The predictive value of microRNA-126 in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Sørensen, Flemming Brandt; Lindebjerg, Jan

    2012-01-01

    MicroRNA-126 is the only microRNA (miRNA) known to be endothelial cell-specific influencing angiogenesis in several ways. The aim of the present study was to analyse the possible predictive value of miRNA-126 in relation to first line capecitabine and oxaliplatin (XELOX) in patients with metastatic...

  15. Deletion of ultraconserved elements yields viable mice

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.

    2007-07-15

    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  16. The Ceremonial Side of Training--Of What Value to First-Line Supervisors?

    Science.gov (United States)

    Adams, Fred P.

    1976-01-01

    A case study to determine whether the recognition of being selected for a training program and the satisfactory completion of it result in increased job satisfaction using 56 first-line supervisors from a textile company. (WL)

  17. A multicenter study of viable PCR using propidium monoazide to detect Legionella in water samples.

    Science.gov (United States)

    Scaturro, Maria; Fontana, Stefano; Dell'eva, Italo; Helfer, Fabrizia; Marchio, Michele; Stefanetti, Maria Vittoria; Cavallaro, Mario; Miglietta, Marilena; Montagna, Maria Teresa; De Giglio, Osvalda; Cuna, Teresa; Chetti, Leonarda; Sabattini, Maria Antonietta Bucci; Carlotti, Michela; Viggiani, Mariagabriella; Stenico, Alberta; Romanin, Elisa; Bonanni, Emma; Ottaviano, Claudio; Franzin, Laura; Avanzini, Claudio; Demarie, Valerio; Corbella, Marta; Cambieri, Patrizia; Marone, Piero; Rota, Maria Cristina; Bella, Antonino; Ricci, Maria Luisa

    2016-07-01

    Legionella quantification in environmental samples is overestimated by qPCR. Combination with a viable dye, such as Propidium monoazide (PMA), could make qPCR (named then vPCR) very reliable. In this multicentre study 717 artificial water samples, spiked with fixed concentrations of Legionella and interfering bacterial flora, were analysed by qPCR, vPCR and culture and data were compared by statistical analysis. A heat-treatment at 55 °C for 10 minutes was also performed to obtain viable and not-viable bacteria. When data of vPCR were compared with those of culture and qPCR, statistical analysis showed significant differences (P 0.05). Overall this study provided a good experimental reproducibility of vPCR but also highlighted limits of PMA in the discriminating capability of dead and live bacteria, making vPCR not completely reliable. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 'Poker' association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study

    International Nuclear Information System (INIS)

    Bruera, Gemma; Ficorella, Corrado; Ricevuto, Enrico; Santomaggio, Alessandra; Cannita, Katia; Baldi, Paola Lanfiuti; Tudini, Marianna; De Galitiis, Federica; Mancini, Maria; Marchetti, Paolo; Antonucci, Adelmo

    2010-01-01

    This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC). Simon two-step design: delta 20% (p 0 50%, p 1 70%), power 80%, α 5%, β 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m 2 , days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m 2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m 2 , days 8, 22; every 4 weeks. Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m 2 . ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%. Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered. Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34

  19. Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.

    Science.gov (United States)

    Wang, Tso-Fu; Chu, Sung-Chao; Lee, Jen-Jyh; Yang, Gee-Gwo; Huang, Wei-Han; Chang, En-Ting; Low, Tissot; Wu, Yi-Feng; Kao, Ruey-Ho; Lin, Chih-Bin

    2017-08-01

    This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients. © 2017 John Wiley & Sons Australia, Ltd.

  20. Predictors of viable germ cell tumor in postchemotherapeutic residual retroperitoneal masses

    Directory of Open Access Journals (Sweden)

    Khalid Al Othman

    2014-01-01

    Full Text Available Objective: The aim of this study was to identify predictors of viable germ cell tumor (GCT in postchemotherapeutic residual retroperitoneal masses. Materials and Methods: The pertinent clinical and pathologic data of 16 male patients who underwent postchemotherapeutic retroperitoneal lymph node dissection (PC-RPLND at King Faisal Specialist Hospital and Research Centre between 1994 and 2005 were reviewed retrospectively. It was found that all patients received cisplatin-based chemotherapy for advanced testicular GCT. Results: Out of the 16 male patients, 2 (13%, 8 (50%, and 6 (37% had viable GCT, fibrosis, and teratoma, respectively. Ten (10 of the patients with prechemotherapeutic S1 tumor markers did not have viable GCT, and two of the six patients who had prechemotherapeutic S2 tumor markers have viable GCT. All tumor marker levels normalized after chemotherapy even in patients with viable GCT. Four patients had vascular invasion without viable GCT. Furthermore, four patients had more than 60% embryonal elements in the original pathology, but only 1 had viable GCT at PC-RPLND. Four of the five patients with immature teratoma had teratoma at PC-RPLND but no viable GCT; however, out of the four patients with mature teratoma, one had viable GCT and two had teratoma at PC-RPLND. Of the two patients with viable GCT, one had 100% embryonal cancer in the original pathology, prechemotherapeutic S2 tumor markers, history of orchiopexy, and no vascular invasion; the other patient had yolk sac tumor with 25% embryonal elements and 40% teratoma in the original pathology, and prechemotherapeutic S2 tumor markers. Conclusion: None of the clinical or pathological parameters showed a strong correlation with the presence of viable GCT in PC-RPLND. However, patients with ≥S2 may be at higher risk to have viable GCT. Further studies are needed to clarify this.

  1. First-line treatment of metastatic melanoma: role of nivolumab

    Directory of Open Access Journals (Sweden)

    Force J

    2017-02-01

    Full Text Available Jeremy Force,1 April KS Salama,1,2 1Division of Hematology/Oncology, Duke University Medical Center, Durham, NC, USA; 2Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA Abstract: Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes. Keywords: PD-1, immunotherapy, pembrolizumab, PD-L1, resistance, checkpoint, BRAF

  2. PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

    Science.gov (United States)

    Vincenzi, Bruno; Santini, Daniele; Schiavon, Gaia; Frezza, Anna Maria; Silletta, Marianna; Crucitti, Pierfilippo; Casali, Paolo; Dei Tos, Angelo P; Rossi, Sabrina; Rizzo, Sergio; Badalamenti, Giuseppe; Tomasino, Rosa Maria; Russo, Antonio; Butrynski, James E; Tonini, Giuseppe

    2012-04-01

    Soft tissue sarcomas are aggressive tumors representing alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. Copyright © 2011 Wiley Periodicals, Inc.

  3. Sustainability of first-line antiretroviral regimens: findings from a large HIV treatment program in western Kenya.

    Science.gov (United States)

    Braitstein, Paula; Ayuo, Paul; Mwangi, Ann; Wools-Kaloustian, Kara; Musick, Beverly; Siika, Abraham; Kimaiyo, Sylvester

    2010-02-01

    To describe first change or discontinuation in combination antiretroviral treatment (cART) among previously treatment naive, HIV-infected adults in a resource-constrained setting. The United States Agency for International Development-Academic Model Providing Access to Healthcare Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout western Kenya. Patients in this analysis were aged > or =18 years, previously antiretroviral treatment naive, and initiated to cART between January 2006 and November 2007, with at least 1 follow-up visit. A treatment change or discontinuation was defined as change of regimen including single drug substitutions or a complete halting of cART. There were 14,162 patients eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed or stopped their cART. Among these, 859 (62%) changed their regimen (including 514 patients who had a single drug substitution) and 517 (38%) completely discontinued cART. The overall incidence rate (IR) of cART changes or stops per 100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The incidence was much higher in the first year of post-cART initiation (IR: 25.0, 95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The most commonly cited reason was toxicity (46%). In multivariate regression, individuals were more likely to discontinue cART if they were World Health Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69] or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88). Individuals were more likely to change their regimen if they were aged > or =38 years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3 (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those receiving

  4. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

    International Nuclear Information System (INIS)

    Edler von Eyben, Finn; Roviello, Giandomenico; Kiljunen, Timo; Kairemo, Kalevi; Joensuu, Timo; Uprimny, Christian; Virgolini, Irene

    2018-01-01

    There is a controversy as to the relative efficacy of 177 Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177 Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Twelve studies including 669 patients reported 177 Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177 Lu-PSMA RLT. The treatment with 177 Lu-PSMA-617 and 177 Lu-PSMA for imaging and therapy (I and T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177 Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). 177 Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ 2 test). Median survival was longer after 177 Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177 Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ 2 test). As for patients with mCRPC, treatment with 177 Lu

  5. Treatment of Helicobacter pylori infection.

    LENUS (Irish Health Repository)

    O'Connor, Anthony

    2012-02-01

    This article aims to examine current best practice in the field reference to first-line, second-line, rescue and emerging treatment regimens for Helicobacter pylori eradication. The recommended first-line treatment in published guidelines in Europe and North American is proton pump inhibitor combined with amoxicillin and clarithromycin being the favoured regimen. Rates of eradication with this regimen however are falling alarmingly due to a combination of antibiotic resistance and poor compliance with therapy. Bismuth based quadruple therapies and levofloxacin based regimes have been shown to be effective second line regimens. Third-line options include regimes based on rifabutin or furazolidone, but susceptibility testing is the most rational option here, but is currently not used widely enough. Sequential therapy is promising but needs further study and validation outside of Italy. Although the success of first line treatments is falling, if compliance is good and a clear treatment paradigm adhered to, almost universal eradication rates can still be achieved. If compliance is not achievable, the problem of antibiotic resistance will continue to beset any combination of drugs used for H. pylori eradication.

  6. Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

    Science.gov (United States)

    Häggblom, Amanda; Santacatterina, Michele; Neogi, Ujjwal; Gisslen, Magnus; Hejdeman, Bo; Flamholc, Leo; Sönnerborg, Anders

    2017-01-01

    Switch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART. Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF). Most patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96) and 3.20 (95% 2.65-3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART. In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

  7. Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

    Directory of Open Access Journals (Sweden)

    Amanda Häggblom

    Full Text Available Switch from first line antiretroviral therapy (ART to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART.Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF.Most patients (n = 495; 57.0% switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2% or without drug resistance mutations (DRM (n = 250; 28.8% experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96 and 3.20 (95% 2.65-3.75, respectively compared with those who switched without VF (4.53 years. Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART.In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

  8. Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

    NARCIS (Netherlands)

    Lambert-Niclot, S.; George, E. C.; Pozniak, A.; White, E.; Schwimmer, C.; Jessen, H.; Johnson, M.; Dunn, D.; Perno, C. F.; Clotet, B.; Plettenberg, A.; Blaxhult, A.; Palmisano, L.; Wittkop, L.; Calvez, V.; Marcelin, A. G.; Raffi, F.; Dedes, Nikos; Chêne, Geneviève; Richert, Laura; Allavena, Clotilde; Raffi, François; Autran, Brigitte; Antinori, Andrea; Bucciardini, Raff Aella; Vella, Stefano; Horban, Andrzej; Arribas, Jose; Babiker, Abdel G.; Boffito, Marta; Pillay, Deenan; Pozniak, Anton; Franquet, Xavier; Schwarze, Siegfried; Grarup, Jesper; Fischer, Aurélie; Wallet, Cédrick; Diallo, Alpha; Molina, Jean-Michel; Saillard, Juliette; Moecklinghoff, Christiane; Stellbrink, Hans-Jürgen; van Leeuwen, Remko; Gatell, Jose; Sandstrom, Eric; Flepp, Markus; Ewings, Fiona; George, Elizabeth C.; Hudson, Fleur; Pearce, Gillian; Quercia, Romina; Rogatto, Felipe; Leavitt, Randi; Nguyen, Bach-Yen; Goebel, Frank; Marcotullio, Simone; Kaur, Navrup; Sasieni, Peter; Spencer-Drake, Christina; Peto, Tim; Miller, Veronica; Arnault, Fabien; Boucherie, Céline; Jean, Delphine; Paniego, Virginie; Paraina, Felasoa; Rouch, Elodie; Schwimmer, Christine; Soussi, Malika; Taieb, Audrey; Termote, Monique; Touzeau, Guillaume; Cursley, Adam; Dodds, Wendy; Hoppe, Anne; Kummeling, Ischa; Pacciarini, Filippo; Paton, Nick; Russell, Charlotte; Taylor, Kay; Ward, Denise; Aagaard, Bitten; Eid, Marius; Gey, Daniela; Jensen, Birgitte Gram; Jakobsen, Marie-Louise; Jansson, Per O.; Jensen, Karoline; Joensen, Zillah Maria; Larsen, Ellen Moseholm; Pahl, Christiane; Pearson, Mary; Nielsen, Birgit Riis; Reilev, Søren Stentoft; Christ, Ilse; Lathouwers, Desiree; Manting, Corry; Mendy, Bienvenu Yves; Metro, Annie; Couffin-Cadiergues, Sandrine; Knellwolf, Anne-Laure; Palmisiano, Lucia; Aznar, Esther; Barea, Cristina; Cotarelo, Manuel; Esteban, Herminia; Girbau, Iciar; Moyano, Beatriz; Ramirez, Miriam; Saiz, Carmen; Sanchez, Isabel; Yllescas, Maria; Binelli, Andrea; Colasanti, Valentina; Massella, Maurizio; Anagnostou, Olga; Gioukari, Vicky; Touloumi, Giota; Schmied, Brigitte; Rieger, Armin; Vetter, Norbert; de Wit, Stephane; Florence, Eric; Vandekerckhove, Linos; Gerstoft, Jan; Mathiesen, Lars; Katlama, Christine; Cabie, Andre; Cheret, Antoine; Dupon, Michel; Ghosn, Jade; Girard, Pierre-Marie; Goujard, Cécile; Lévy, Yves; Morlat, Philippe; Neau, Didier; Obadia, Martine; Perre, Philippe; Piroth, Lionel; Reynes, Jacques; Tattevin, Pierre; Ragnaud, Jean Marie; Weiss, Laurence; Yazdan, Yazdanpanah; Yeni, Patrick; Zucman, David; Behrens, Georg; Esser, Stefan; Fätkenheuer, Gerd; Hoffmann, Christian; Jessen, Heiko; Rockstroh, Jürgen; Schmidt, Reinhold; Stephan, Christoph; Unger, Stefan; Hatzakis, Angelos; Daikos, George L.; Papadopoulos, Antonios; Skoutelis, Athamasios; Banhegyi, Denes; Mallon, Paddy; Mulcahy, Fiona; Andreoni, Massimo; Bonora, Stefano; Castelli, Francesco; Monforte, Antonella D.'Arminio; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Mazzotta, Francesco; Carlo, Torti; Vullo, Vincenzo; Prins, Jan; Richter, Clemens; Verhagen, Dominique; van Eeden, Arne; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Sarmento-Castro, Rui; Garcia, Juan Gonzalez; Aldeguer, José López; Clotet, Bonaventura; Domingo, Pere; Gatell, Jose M.; Knobel, Hernando; Marquez, Manuel; Miralles, Martin Pilar; Portilla, Joaquin; Soriano, Vicente; Tellez, Maria-Jesus; Thalme, Anders; Blaxhult, Anders; Gisslen, Magnus; Winston, Alan; Fox, Julie; Gompels, Mark; Herieka, Elbushra; Johnson, Margaret; Leen, Clifford; Teague, Alastair; Williams, Ian; Boyd, Mark Alastair; Møller, Nina Friis; Larsen, Ellen Frøsig Moseholm; Le Moing, Vincent; Wit, Ferdinand W. N. M.; Kowalska, Justyna; Berenguer, Juan; Moreno, Santiago; Müller, Nicolas J.; Török, Estée; Post, Frank; Angus, Brian; Calvez, Vincent; Boucher, Charles; Collins, Simon; Dunn, David; Lambert, Sidonie; Marcelin, Anne-Geneviève; Perno, Carlo Federico; White, Ellen; Ammassari, Adriana; Stoehr, Wolgang; Schmidt, Reinhold Ernst; Odermarsky, Michal; Smith, Colette; Thiébaut, Rodolphe; de La Serna, Jose Ignacio Bernardino; Castagna, Antonella; Furrer, Hans-Jackob; Mocroft, Amanda; Reiss, Peter; Bucciardini, Raffaella; Fragola, Vincenzo; Lauriola, Marco; Murri, Rita; Nieuwkerk, Pythia; Spire, Bruno; Volny-Anne, Alain; West, Brian; Amieva, Hélène; Llibre Codina, Josep Maria; Braggion, Marco; Focà, Emanuele

    2016-01-01

    To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and

  9. First on-line positron experiments en route to pair-plasma creation

    Energy Technology Data Exchange (ETDEWEB)

    Stanja, Juliane; Hergenhahn, Uwe; Stenson, Eve V. [Max-Planck-Institut fuer Plasmaphysik (Germany); Niemann, Holger; Sunn Pedersen, Thomas [Max-Planck-Institut fuer Plasmaphysik (Germany); Ernst-Moritz-Arndt Universitaet Greifswald (Germany); Saitoh, Haruhiko [Max-Planck-Institut fuer Plasmaphysik (Germany); The University of Tokyo (Japan); Stoneking, Matthew R. [Lawrence University (United States); Hugenschmidt, Christoph; Piochacz, Christian [Technische Universitaet Muenchen (Germany); Schweikhard, Lutz [Ernst-Moritz-Arndt Universitaet Greifswald (Germany)

    2016-07-01

    Electron-positron plasmas are predicted to show a fundamentally different behavior from traditional ion-electron plasmas, because of the equal masses of the two species. Using up to 10{sup 9} positrons per second provided by the NEPOMUC (Neutron-Induced Positron Source Munich) facility, the APEX/PAX team aims to create the first such plasma confined in a toroidal magnetic trap. Positron beam parameters as well as efficient injection and confinement schemes for both species in toroidal geometries are fundamental to the project. In this contribution we present results from first on-line positron experiments. Besides characterizing the NEPOMUC beam we conducted positron injection experiments into a dipole magnetic field configuration. Using static electric fields, a 5-eV positron beam was transported across magnetic field lines into the confinement region. With this method, up to 38% of the incoming particles reach the confinement region and make at least a 180 revolution around the magnet. Under dedicated experimental conditions confinement on the order of 1 ms was realized.

  10. Treatment paradigms for advanced stage non-small cell lung cancer in the era of multiple lines of therapy.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2009-02-01

    The duration of first-line and the timing of second-line therapy for advanced non-small cell lung cancer has been an area of recent investigation. Five trials have been performed that have investigated shorter (3-4 cycles) versus longer duration of platinum-based therapy; four trials revealed an equivalent overall survival with the shorter duration of therapy, and one trial revealed superior survival with the longer duration of therapy. The toxicity and quality of life data has either been equivalent or favored the shorter duration of therapy. Two trials have investigated the timing of a second-line therapy after completion of four cycles of platinum-based therapy versus the standard treatment paradigm of initiating second-line therapy upon disease progression. Both of these trials have revealed a statistically significant improvement in the progression-free survival, and a trend towards improved survival for the earlier use of second-line therapy. Only 50 to 60% of patients on the standard treatment arm initiated second-line therapy, and the promising results observed are most likely related to the fact that a higher percentage of patients received second-line therapy on the experimental arm. Several trials have investigated maintenance chemotherapy, and these trials have not revealed a survival benefit probably due to the fact that many patients experience disease progression or unacceptable toxicity during the initial or maintenance therapy. The addition of a targeted agent (bevacizumab or cetuximab) to the initial chemotherapy and the continuation of the targeted agent after completion of the chemotherapy have yielded superior overall survival in comparison to chemotherapy alone. The incremental benefit of the maintenance therapy with the targeted agent is unknown.

  11. Viro-immunological response of drug-naive HIV-1-infected patients starting a first-line regimen with viraemia >500,000 copies/ml in clinical practice.

    Science.gov (United States)

    Santoro, Maria Mercedes; Di Carlo, Domenico; Armenia, Daniele; Zaccarelli, Mauro; Pinnetti, Carmela; Colafigli, Manuela; Prati, Francesca; Boschi, Andrea; Antoni, Anna Maria Degli; Lagi, Filippo; Sighinolfi, Laura; Gervasoni, Cristina; Andreoni, Massimo; Antinori, Andrea; Mussini, Cristina; Perno, Carlo Federico; Borghi, Vanni; Sterrantino, Gaetana

    2017-09-22

    Virological success (VS) and immunological reconstitution (IR) of antiretroviral-naive HIV-1-infected patients with pre-therapy viral load (VL) >500,000 copies/ml was assessed after 12 months of treatment according to initial drug-class regimens. An observational multicentre retrospective study was performed. VS was defined as the first VL 500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.

  12. Treatment of ectopic first permanent molar teeth.

    Science.gov (United States)

    Hennessy, Joe; Al-Awadhi, E A; Dwyer, Lian O; Leith, Rona

    2012-11-01

    Ectopic eruption of the first permanent molar is a relatively common occurence in the developing dentition. A range of treatment options are available to the clinician provided that diagnosis is made early. Non-treatment can result in premature exfoliation of the second primary molar, space loss and impaction of the second premolar. This paper will describe the management of ectopic first permanent molars, using clinical examples to illustrate the available treatment options. This paper is relevant to every general dental practitioner who treats patients in mixed dentition.

  13. Cumulative clinical experience from a decade of use: imatinib as first-line treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Baran Y

    2012-11-01

    Full Text Available Yusuf Baran,1 Guray Saydam21Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey; 2Department of Hematology, School of Medicine, Ege University, Izmir, TurkeyAbstract: Chronic myeloid leukemia (CML is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+ chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs exerting their effect against the oncogenic breakpoint cluster region (BCR-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib- resistant or intolerant CML patients compared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.Keywords: drug resistance, tyrosine kinase inhibitors, chronic myeloid leukemia, imatinib, BCR/ABL

  14. Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.

    Science.gov (United States)

    Etiebet, Mary-Ann A; Shepherd, James; Nowak, Rebecca G; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, Olufunmilayo; Ndembi, Nicaise; Abimiku, Alashle; Carr, Jean K; Eyzaguirre, Lindsay M; Blattner, William A

    2013-02-20

    In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

  15. Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation

    Directory of Open Access Journals (Sweden)

    James K. Hoffman

    2015-01-01

    Full Text Available Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone.

  16. Short-course thrombolysis as the first line of therapy for cardiac valve thrombosis.

    Science.gov (United States)

    Manteiga, R; Carlos Souto, J; Altès, A; Mateo, J; Arís, A; Dominguez, J M; Borrás, X; Carreras, F; Fontcuberta, J

    1998-04-01

    To retrospectively evaluate the clinical and echocardiographic criteria of thrombolytic therapy for mechanical heart valve thrombosis. Nineteen consecutive patients with 22 instances of prosthetic heart valve thrombosis (14 mitral, 2 aortic, 3 tricuspid, and 3 pulmonary) were treated with short-course thrombolytic therapy as first option of treatment in absence of contraindications. The thrombolytic therapy protocol consisted of streptokinase (1,500,000 IU in 90 minutes) (n = 18) in one (n = 7) or two (n = 11) cycles or recombinant tissue-type plasminogen activator (100 mg in 90 minutes) (n = 4). Overall success was seen in 82%, immediate complete success in 59%, and partial success in 23%. Six patients without total response to thrombolytic therapy underwent surgery, and pannus was observed in 83%. Six patients showed complications: allergy, stroke, transient ischemic attack, coronary embolism, minor bleeding, and one death. At diagnosis, 10 patients evidenced atrial thrombus by transesophageal echocardiography, 3 of whom experienced peripheral embolism during thrombolysis. Four episodes of rethrombosis were observed (16%). The survivorship was 84% with a mean follow-up of 42.6 months. A short-course of thrombolytic therapy may be considered first-line therapy for prosthetic heart valve thrombosis. The risk of peripheral embolism may be evaluated for the presence of atrial thrombus by transesophageal echocardiography at diagnosis.

  17. Second-Line Therapy for Advanced NSCLC.

    Science.gov (United States)

    Weiss, Jared M; Stinchcombe, Thomas E

    2013-01-01

    Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.

  18. Time since start of first-line therapy as a predictive clinical marker for nintedanib in patients with previously treated non-small cell lung cancer

    DEFF Research Database (Denmark)

    Gaschler-Markefski, Birgit; Sikken, Patricia; Heymach, John V

    2017-01-01

    INTRODUCTION: No predictive clinical or genetic markers have been identified or validated for antiangiogenic agents in lung cancer. We aimed to identify a predictive clinical marker of benefit for nintedanib, an angiokinase inhibitor, using data from two large second-line non-small cell lung cancer...... Phase III trials (LUME-Lung 1 ([LL1] and LUME-Lung 2). METHODS: Predictive marker identification was conducted in a multi-step process using data from both trials; a hypothesis was generated, confirmed and validated. Statistical analyses included a stepwise selection approach, a recursive partitioning...... method and the evaluation of HRs, including treatment-by-covariate interactions. The marker was finally validated using a prospectively defined hierarchical testing procedure and treatment-by-covariate interaction for overall survival (OS) based on LL1. RESULTS: Time since start of first-line therapy...

  19. Treatment of ectopic first permanent molar teeth.

    LENUS (Irish Health Repository)

    Hennessy, Joe

    2012-11-01

    Ectopic eruption of the first permanent molar is a relatively common occurence in the developing dentition. A range of treatment options are available to the clinician provided that diagnosis is made early. Non-treatment can result in premature exfoliation of the second primary molar, space loss and impaction of the second premolar. This paper will describe the management of ectopic first permanent molars, using clinical examples to illustrate the available treatment options. CLINICAL RELEVANCE: This paper is relevant to every general dental practitioner who treats patients in mixed dentition.

  20. Lambing behaviour of Merino ewes from lines subjected to divergent ...

    African Journals Online (AJOL)

    No line difference was observed in the period that ewes spent grooming. Ewes caring for viable multiples groomed their offspring for a longer period than those caring for singles. Mature ewes tended to groom their lambs for a longer period than primi-parous maidens. A higher proportion of High (H) line ewes groomed their ...

  1. The first year of management of the 'Nocera Superiore' wastewater treatment plant

    International Nuclear Information System (INIS)

    De Feo, G.; De Gisi, S.; Ferrante, A.; Galasso, M.; De Rosa, R.; Giuliani, A.; Guadagnolo, S.; Pucci, L.

    2009-01-01

    The wastewater treatment plant (WWTP) of Nocera Superiore, in the province of Salerno, in Southern Italy, was realized for the treatment of urban wastewater on behalf of the Special Project called 'CASMEZ per il Disinquinamento del Golfo di Napoli' (PS3). The WWTP was designed for 300,000 Equivalent Inhabitants during the summer period and it is based on the classic activated sludge process for the biological treatment of wastewater. Moreover, it has the anaerobic digestion of sludge but it does not use the primary sedimentation: this is the principal peculiarity of the plant. In this paper, after an accurate description of water and sludge lines, parameters related to the first year of functioning of the plant (2007) are deeply presented and discussed. Moreover, inlet and outlet wastewater are characterised with regard to the principal parameters (BOD5, COD, TSS, etc.). Finally, the removal efficacy for the parameters considered are represented in terms of applied and removed loads, showing a linear relationship. The performed analysis pointed out that the plant has functioned under its potentiality, but respecting the compliance limits. [it

  2. Administering Spatial and Cognitive Instruments In-class and On-line: Are These Equivalent?

    Science.gov (United States)

    Williamson, Kenneth C.; Williamson, Vickie M.; Hinze, Scott R.

    2017-02-01

    Standardized, well-established paper-and-pencil tests, which measure spatial abilities or which measure reasoning abilities, have long been found to be predictive of success in the STEM (science, technology, engineering, and mathematics) fields. Instructors can use these tests for prediction of success and to inform instruction. A comparative administration of spatial visualization and cognitive reasoning tests, between in-class (proctored paper and pencil) and on-line (unproctored Internet) ( N = 457), was used to investigate and to determine whether the differing instrument formats yielded equal measures of spatial ability and reasoning ability in large first-semester general chemistry sections. Although some gender differences were found, findings suggest that some differences across administration formats, but that on-line administration had similar properties of predicting chemistry performance as the in-class version. Therefore, on-line administration is a viable option for instructors to consider especially when dealing with large classes.

  3. Second-line treatment of recurrent HNSCC: tumor debulking in combination with high-dose-rate brachytherapy and a simultaneous cetuximab-paclitaxel protocol

    International Nuclear Information System (INIS)

    Ritter, M.; Teudt, I. U.; Meyer, J. E.; Schröder, U.; Kovács, G.; Wollenberg, B.

    2016-01-01

    After the failure of first-line treatment, the clinical prognosis in head and neck cancer (HNSCC) deteriorates. Effective therapeutic strategies are limited due to the toxicity of previous treatments and the diminished tolerance of surrounding normal tissue. This study demonstrates a promising second-line regimen, with function preserving surgical tumor debulking, followed by a combination of postoperative interstitial brachytherapy and a simultaneous protocol of cetuximab and taxol. From January 2006 to May 2013, 197 patients with HNSCC were treated with brachytherapy at the University Hospital Schleswig-Holstein Campus Lübeck, including 94 patients due to recurrent cancer. Within these, 18 patients were referred to our clinic because of early progressive disease following first- or second-line treatment failure. They received the new palliative regimen. A matched-pair analysis including recurrent tumor stage, status of resection margins, tissue invasion and previous therapy was performed to evaluate this treatment retrospectively. Overall survival (OS), disease-free survival (DFS), functional outcome and treatment toxicity was analyzed on the basis of medical records and follow-up data. DFS and OS of the study group were 8.7 and 14.8 months. Whereas, DFS and OS of the control group, treated only by function preserving tumor debulking and brachytherapy, was 3.9 and 6.1 months respectively. This demonstrates a positive trend through the additional use of the cetuximab-taxane protocol. Furthermore, no increase of therapy induced toxicities was displayed. Pre-treated patients with a further relapse benefit from the ‘cetuximab-taxane recurrency scheme’. It seems to be a valuable complement to interdisciplinary and multimodal tumor therapy, which improves OS and results in acceptable toxicity. The online version of this article (doi:10.1186/s13014-016-0583-0) contains supplementary material, which is available to authorized users

  4. Treatment of produced water: is a flotation viable process?; Tratamento da agua produzida: a flotacao e um processo viavel?

    Energy Technology Data Exchange (ETDEWEB)

    Santana, Claudia Ramos; Freitas, Andrea Goncalves Bueno de; Silva, Gabriel Francisco da; Paixao, Ana Eleonora Almeida [Universidade Federal de Sergipe (UFS), Aracaju, SE (Brazil); Oliveira, Rosivania da Paixao Silva [Fundacao de Apoio a Pesquisa e Extensao de Sergipe (FAPESE), Aracaju, SE (Brazil)

    2008-07-01

    In petroleum oil wells there comes a situation when most of the oil drilled accompanies a large amount of water. This may be due to the proper conditions of the reservoir or as a consequence of the water injection in the secondary recovery processes from the well. The amount of produced water together with oil can vary to a great extent and it frequently attains to about 50% of the drilled oil. One technique employed for the treatment of industrial effluents, mainly the oily ones which is of great interest is that of flotation. This phenomenon is being extensively used for oil removal from emulsified oils in various areas, such as that of dissolved air flotation (DAF) and the induced air flotation (IAF). The conventional flotation processes consist of the following stages: bubble gas generation (normally air) from the interior of the effluent; collision between the gas bubbles and the suspended oil drops in the water; adhesion of the gas bubbles in the oil drops and ascension of aggregate oil drops/bubbles until the surface, where the oil is removed. This work seeks to contribute for the understanding of the factors which contribute for the selection of the flotation process as one of the methods most viable for the treatment of the produced water. (author)

  5. 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

  6. Optimum field size and choice of isodose lines in electron beam treatment

    International Nuclear Information System (INIS)

    Das, Indra J.; Cheng, Chee W.; Healey, Glenn A.

    1995-01-01

    Purpose: A method is provided for the optimum field size and the choice of isodose line for the dose prescription in electron beam therapy. Methods and Materials: Electron beam dose uniformity was defined in terms of target coverage factor (TCF) which is an index of dose coverage of a given treatment volume. The TCF was studied with respect to the field size, the beam energy, and the isodose level for prescription from the measured data for various accelerators. The effect of the TCF on air gap between electron applicator/cone and the surface was investigated. Electron beams from scattering foil and scanned beam units were analyzed for the target coverage. Results: A mathematical method is provided to optimize a field size for target coverage by a given isodose line in terms of TCF which is strongly dependent on the type of accelerator and the design of the collimator. For a given type of collimating system, the TCF does not depend on the type of electron beam production (scattering foil or swept scanned beam). Selection of isodose line for dose prescription is very critical for the value of the TCF and the dose coverage. The TCF is inversely proportional to the isodose value selected for the treatment and nearly linear with field size and beam energy. Air gap between applicator and the surface reduces the dose uniformity. Tertiary collimator moderately improves the lateral coverage for high energy beams. Conclusions: To adequately cover the target volume in electron beam treatment, lateral and depth coverage should be considered. The coverage at depth is strongly dependent on the choice of isodose line or beam normalization. If the dose prescription is at d max (i.e., the 100% isodose line is selected), the choice of beam energy is not critical for depth coverage since d max is nearly independent of energy for smaller fields. The 100% isodose line should not be chosen for treatment because of the significant constriction of this isodose line and inadequate

  7. Current Perspectives on Viable but Non-culturable State in Foodborne Pathogens

    OpenAIRE

    Zhao, Xihong; Zhong, Junliang; Wei, Caijiao; Lin, Chii-Wann; Ding, Tian

    2017-01-01

    The viable but non-culturable (VBNC) state, a unique state in which a number of bacteria respond to adverse circumstances, was first discovered in 1982. Unfortunately, it has been reported that many foodborne pathogens can be induced to enter the VBNC state by the limiting environmental conditions during food processing and preservation, such as extreme temperatures, drying, irradiation, pulsed electric field, and high pressure stress, as well as the addition of preservatives and disinfectant...

  8. Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

    Science.gov (United States)

    Tan, Chongqing; Peng, Liubao; Zeng, Xiaohui; Li, Jianhe; Wan, Xiaomin; Chen, Gannong; Yi, Lidan; Luo, Xia; Zhao, Ziying

    2013-01-01

    First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

  9. Budget Impact Analysis of Afatinib for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 Substitution Mutations in a U.S. Health Plan.

    Science.gov (United States)

    Graham, Jonathan; Earnshaw, Stephanie; Burslem, Kate; Lim, Jonathan

    2018-06-01

    Afatinib is 1 of 3 tyrosine kinase inhibitors approved in the United States for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions (del19) or exon 21 (L858R) substitution mutations. In clinical trials, afatinib has demonstrated improvement in progression-free survival versus standard chemotherapy and gefitinib. To analyze the impact of increases in afatinib treatment share on the cost and health outcomes in a commercial health plan in the United States. A decision model was developed to evaluate the budget impact of increases in afatinib share for the first-line treatment of patients with metastatic NSCLC with EGFR del19 or L858R substitution mutations over a 5-year time horizon. The model compared the total annual costs for a health plan with 1 million covered lives in a scenario in which afatinib share increased 5 percentage points annually to one in which all treatment shares remained constant over time. The number of patients eligible for treatment was estimated using published incidence data. Therapies included in the model were afatinib, erlotinib, gefitinib, and the chemotherapy doublet, pemetrexed in combination with cisplatin. The mean time spent by patients in progression-free and progressive disease states was based on survival data from clinical trials and a network meta-analysis. Therapy-related costs included monthly drug acquisition and administration costs and costs of managing adverse reactions. Disease management costs were also assessed in the model. Scenario analyses were performed to assess alternative scenarios of afatinib treatment share. Additionally, a one-way sensitivity analysis was performed to test the robustness of the model, given parameter uncertainty. Using the base-case parameter assumptions and a 5-percentage-point annual increase in afatinib treatment share, we estimated the total budget increases in years 1 through 5

  10. Viable Mycobacterium avium ssp. paratuberculosis isolated from calf milk replacer.

    Science.gov (United States)

    Grant, Irene R; Foddai, Antonio C G; Tarrant, James C; Kunkel, Brenna; Hartmann, Faye A; McGuirk, Sheila; Hansen, Chungyi; Talaat, Adel M; Collins, Michael T

    2017-12-01

    When advising farmers on how to control Johne's disease in an infected herd, one of the main recommendations is to avoid feeding waste milk to calves and instead feed calf milk replacer (CMR). This advice is based on the assumption that CMR is free of viable Mycobacterium avium ssp. paratuberculosis (MAP) cells, an assumption that has not previously been challenged. We tested commercial CMR products (n = 83) obtained from dairy farms around the United States by the peptide-mediated magnetic separation (PMS)-phage assay, PMS followed by liquid culture (PMS-culture), and direct IS900 quantitative PCR (qPCR). Conventional microbiological analyses for total mesophilic bacterial counts, coliforms, Salmonella, coagulase-negative staphylococci, streptococci, nonhemolytic Corynebacterium spp., and Bacillus spp. were also performed to assess the overall microbiological quality of the CMR. Twenty-six (31.3%) of the 83 CMR samples showed evidence of the presence of MAP. Seventeen (20.5%) tested positive for viable MAP by the PMS-phage assay, with plaque counts ranging from 6 to 1,212 pfu/50 mL of reconstituted CMR (average 248.5 pfu/50 mL). Twelve (14.5%) CMR samples tested positive for viable MAP by PMS-culture; isolates from all 12 of these samples were subsequently confirmed by whole-genome sequencing to be different cattle strains of MAP. Seven (8.4%) CMR samples tested positive for MAP DNA by IS900 qPCR. Four CMR samples tested positive by both PMS-based tests and 5 CMR samples tested positive by IS900 qPCR plus one or other of the PMS-based tests, but only one CMR sample tested positive by all 3 MAP detection tests applied. All conventional microbiology results were within current standards for whole milk powders. A significant association existed between higher total bacterial counts and presence of viable MAP indicated by either of the PMS-based assays. This represents the first published report of the isolation of viable MAP from CMR. Our findings raise concerns

  11. TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

    International Nuclear Information System (INIS)

    Schneiderman, Rosa S; Shmueli, Esther; Kirson, Eilon D; Palti, Yoram

    2010-01-01

    Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin. Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt R1 ; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs. TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells. The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors

  12. Third-line treatment and {sup 177}Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Edler von Eyben, Finn [Center of Tobacco Control Research, Odense (Denmark); Roviello, Giandomenico [San Donato Hospital, Department of Oncology, Medical Oncology Unit, Arezzo (Italy); University of Trieste, Department Medical, Surgery, and Health Sciences, Trieste (Italy); Kiljunen, Timo; Kairemo, Kalevi; Joensuu, Timo [Docrates Cancer Center, Helsinki (Finland); Uprimny, Christian; Virgolini, Irene [University Hospital Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

    2018-03-15

    There is a controversy as to the relative efficacy of {sup 177}Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether {sup 177}Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Twelve studies including 669 patients reported {sup 177}Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with {sup 177}Lu-PSMA RLT. The treatment with {sup 177}Lu-PSMA-617 and {sup 177}Lu-PSMA for imaging and therapy (I and T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. {sup 177}Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). {sup 177}Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ{sup 2} test). Median survival was longer after {sup 177}Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for {sup 177}Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ{sup 2

  13. Grazing of particle-associated bacteria-an elimination of the non-viable fraction.

    Science.gov (United States)

    Gonsalves, Maria-Judith; Fernandes, Sheryl Oliveira; Priya, Madasamy Lakshmi; LokaBharathi, Ponnapakkam Adikesavan

    Quantification of bacteria being grazed by microzooplankton is gaining importance since they serve as energy subsidies for higher trophic levels which consequently influence fish production. Hence, grazing pressure on viable and non-viable fraction of free and particle-associated bacteria in a tropical estuary controlled mainly by protist grazers was estimated using the seawater dilution technique. In vitro incubations over a period of 42h showed that at the end of 24h, growth coefficient (k) of particle-associated bacteria was 9 times higher at 0.546 than that of free forms. Further, 'k' value of viable cells on particles was double that of free forms at 0.016 and 0.007, respectively. While bacteria associated with particles were grazed (coefficient of removal (g)=0.564), the free forms were relatively less grazed indicating that particle-associated bacteria were exposed to grazers in these waters. Among the viable and non-viable forms, 'g' of non-viable fraction (particle-associated bacteria=0.615, Free=0.0086) was much greater than the viable fraction (particle-associated bacteria=0.056, Free=0.068). Thus, grazing on viable cells was relatively low in both the free and attached states. These observations suggest that non-viable forms of particle-associated bacteria were more prone to grazing and were weeded out leaving the viable cells to replenish the bacterial standing stock. Particle colonization could thus be a temporary refuge for the "persistent variants" where the viable fraction multiply and release their progeny. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  14. Grazing of particle-associated bacteria-an elimination of the non-viable fraction

    Directory of Open Access Journals (Sweden)

    Maria-Judith Gonsalves

    Full Text Available Abstract Quantification of bacteria being grazed by microzooplankton is gaining importance since they serve as energy subsidies for higher trophic levels which consequently influence fish production. Hence, grazing pressure on viable and non-viable fraction of free and particle-associated bacteria in a tropical estuary controlled mainly by protist grazers was estimated using the seawater dilution technique. In vitro incubations over a period of 42 h showed that at the end of 24 h, growth coefficient (k of particle-associated bacteria was 9 times higher at 0.546 than that of free forms. Further, ‘k’ value of viable cells on particles was double that of free forms at 0.016 and 0.007, respectively. While bacteria associated with particles were grazed (coefficient of removal (g = 0.564, the free forms were relatively less grazed indicating that particle-associated bacteria were exposed to grazers in these waters. Among the viable and non-viable forms, ‘g’ of non-viable fraction (particle-associated bacteria = 0.615, Free = 0.0086 was much greater than the viable fraction (particle-associated bacteria = 0.056, Free = 0.068. Thus, grazing on viable cells was relatively low in both the free and attached states. These observations suggest that non-viable forms of particle-associated bacteria were more prone to grazing and were weeded out leaving the viable cells to replenish the bacterial standing stock. Particle colonization could thus be a temporary refuge for the “persistent variants” where the viable fraction multiply and release their progeny.

  15. Investigation of Wear Behaviour of Sewn Assemblies of Viscose Linings with Different Treatment

    Directory of Open Access Journals (Sweden)

    Dainora BAČKAUSKAITĖ

    2011-07-01

    Full Text Available Different types of chemical treatment of textile are widely applied in advanced textile. Finishing of textile can provide additional functional properties for products or/and to improve the appearance of final product as well as to improve their mechanical properties. In this research the influence of the industrial treatment of viscose linings on the parameters of fabric surface friction, on fabric surface appearance as well as on the slippage resistance of yarns at a seam was investigated. Raw, dyed, dyed and softened, dyed and non-slip finished plain weaved linings were investigated. The slippage resistance of yarns at a seam in woven fabrics was evaluated according to standard EN ISO 13936-1:2004. The friction was investigated according to the standard DIN 53375 in a fabric-fabric friction pair. Surface of raw, dyed, dyed and softened viscose lining was investigated using SEM. The obtained results have shown that the friction parameters as well as the parameters of seam slippage resistance of dyed or dyed and softened fabrics were higher than the ones of raw fabric. The highest differences in those parameters were obtained for lining that was dyed and treated with non-slip finishing. That type of finishing influenced the break of lining yarns without typical to the other investigated linings slipping near a stitching line.http://dx.doi.org/10.5755/j01.ms.17.2.485

  16. LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    L. L. Vysotskaya

    2015-01-01

    Full Text Available Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib and second line (nilotinib, overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

  17. Do Veterans With Posttraumatic Stress Disorder Receive First-Line Pharmacotherapy? Results From the Longitudinal Veterans Health Survey

    Science.gov (United States)

    Greenbaum, Mark A.; Rosen, Craig S.

    2012-01-01

    Objective: Guidelines addressing the treatment of veterans with posttraumatic stress disorder (PTSD) strongly recommend a therapeutic trial of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This study examined veteran characteristics associated with receiving such first-line pharmacotherapy, as well as how being a veteran of the recent conflicts in Afghanistan and Iraq impact receipt of pharmacotherapy for PTSD. Method: This was a national study of 482 Veterans Affairs (VA) outpatients between the ages of 18 and 69 years who had been newly diagnosed with PTSD (DSM-IV criteria: 309.81) during a VA outpatient visit between May 31, 2006, and December 7, 2007. Participants completed a mailed survey between August 11, 2006, and April 6, 2008. Veterans from the Afghanistan and Iraq conflicts and female veterans were intentionally oversampled. Logistic regression models were developed to predict 2 dependent variables: odds of initiating an SSRI/SNRI and, among veterans who initiated an SSRI/SNRI, odds of receiving an adequate therapeutic trial. Each dependent variable was regressed on a variety of sociodemographic and survey characteristics. Results: Of the 377 veterans prescribed a psychotropic medication, 73% (n = 276) received an SSRI/SNRI, of whom 61% (n = 168) received a therapeutic trial. Afghanistan and Iraq veterans were less likely to receive a therapeutic trial (odds ratio [OR] = 0.45; 95% CI, 0.27–0.75; P < .01), with presence of a comorbid depression diagnosis in the year after the index episode moderating this relationship, which further decreased the odds of completing a therapeutic trial (OR = 0.29; 95% CI, 0.09–0.95; P < .05). Conclusions: Reduced levels of receipt of first-line pharmacotherapy among recent veteran returnees parallel previous findings of less mental health treatment utilization in this population and warrant investigation. PMID:22943028

  18. Regulation of Viable and Optimal Cohorts

    Energy Technology Data Exchange (ETDEWEB)

    Aubin, Jean-Pierre, E-mail: aubin.jp@gmail.com [VIMADES (Viabilité, Marchés, Automatique, Décisions) (France)

    2015-10-15

    This study deals with the evolution of (scalar) attributes (resources or income in evolutionary demography or economics, position in traffic management, etc.) of a population of “mobiles” (economic agents, vehicles, etc.). The set of mobiles sharing the same attributes is regarded as an instantaneous cohort described by the number of its elements. The union of instantaneous cohorts during a mobile window between two attributes is a cohort. Given a measure defining the number of instantaneous cohorts, the accumulation of the mobile attributes on a evolving mobile window is the measure of the cohort on this temporal mobile window. Imposing accumulation constraints and departure conditions, this study is devoted to the regulation of the evolutions of the attributes which are1.viable in the sense that the accumulations constraints are satisfied at each instant;2.and, among them, optimal, in the sense that both the duration of the temporal mobile window is maximum and that the accumulation on this temporal mobile window is the largest viable one. This value is the “accumulation valuation” function. Viable and optimal evolutions under accumulation constraints are regulated by an “implicit Volterra integro-differential inclusion” built from the accumulation valuation function, solution to an Hamilton–Jacobi–Bellman partial differential equation under constraints which is constructed for this purpose.

  19. 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...... a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin...... was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P

  20. Feasibility and clinical value of CT-guided {sup 125}I brachytherapy for metastatic soft tissue sarcoma after first-line chemotherapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Mo, Zhiqiang; Zhang, Yanling; Xiang, Zhanwang; Yan, Huzhen; Zhong, Zhihui; Gao, Fei; Zhang, Fujun [Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou (China); Zhang, Tao [Guangzhou Medical University, Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children' s Medical Centre, Guangzhou (China)

    2018-03-15

    To evaluate the feasibility and usefulness of computed tomography (CT)-guided iodine{sup 125} ({sup 125}I) brachytherapy for patients with metastatic soft tissue sarcoma (STS) after first-line chemotherapy failure. We recruited 93 patients with metastatic STS who had received first-line chemotherapy 4-6 times but developed progressive disease, from January 2010 to July 2015; 45 patients who had combined {sup 125}I brachytherapy and second-line chemotherapy (Group A), and 48 patients who received second-line CT only (Group B). In Group A, 49 {sup 125}I seed implantation procedures were performed in 45 patients with 116 metastatic lesions; the primary success rate was 91.1% (41/45), without life-threatening complications. Local control rates at 3, 6, 12, 24 and 36 months were 71.1%, 62.2%, 46.7%, 28.9% and 11.1% for Group A, and 72.9%, 54.2%, 18.8%, 6.3% and 0% for Group B. Mean progression-free survival differed significantly (Group A: 7.1±1.3 months; Group B: 3.6 ±1.1 months; P<0.001; Cox proportional hazards regression analysis), but overall survival did not significantly differ (Group A: 16.9 ±5.1 months; Group B: 12.1 ± 4.8 months). Group A showed better symptom relief and quality of life than Group B. CT-guided {sup 125}I brachytherapy is a feasible and valuable treatment for patients with metastatic STS. (orig.)

  1. Ifosfamide and mitoxantrone as first-line chemotherapy for metastatic breast cancer.

    Science.gov (United States)

    Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Bianco, A; Lacava, J A; Rodriguez, R; Cuevas, M A

    1993-03-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of ifosfamide (IFX) and mitoxantrone (MXN) as first-line chemotherapy for metastatic breast carcinoma. Between January 1990 and August 1991, 48 patients with metastatic breast cancer were entered onto the study. Therapy consisted of IFX 2 g/m2 given as a 1-hour intravenous (IV) infusion on days 1 to 3; mesna 400 mg/m2 as an IV bolus immediately before and 4 hours after IFX administration and 2,000 mg orally 8 hours after IFX administration on days 1 to 3; and MXN 12 mg/m2 as an i.v. bolus on day 3. Cycles were repeated every 21 days until progressive disease (PD) or severe toxicity developed. One patient was considered not assessable for response. Objective regression (OR) was observed in 28 of 47 patients (60%; 95% confidence interval, 46% to 74%). Six patients (13%) had a complete response (CR) and 22 (47%) had a partial response (PR). The median time to treatment failure for the whole group was 9 months (range, 1 to 28); median survival was 19 months (range, 2 to 28). There were no treatment-related deaths. The limiting toxicity was myelosuppression. Leukopenia occurred in 37 patients (77%) and was grade 3 or 4 in 19 patients (40%). Nausea and vomiting were observed in 38 patients (80%), mucositis in 16 patients (33%), and grade 2 hematuria in two patients (4%). Eight patients (16%) developed mild neurotoxicity. The combination of IFX plus MXN is an active regimen against metastatic breast cancer with moderate toxicity that deserves further evaluation.

  2. Droplet digital PCR improves absolute quantification of viable lactic acid bacteria in faecal samples.

    Science.gov (United States)

    Gobert, Guillaume; Cotillard, Aurélie; Fourmestraux, Candice; Pruvost, Laurence; Miguet, Jean; Boyer, Mickaël

    2018-03-14

    Analysing correlations between the observed health effects of ingested probiotics and their survival in digestive tract allows adapting their preparations for food. Tracking ingested probiotic in faecal samples requires accurate and specific tools to quantify live vs dead cells at strain level. Traditional culture-based methods are simpler to use but they do not allow quantifying viable but non-cultivable (VBNC) cells and they are poorly discriminant below the species level. We have set up a viable PCR (vPCR) assay combining propidium monoazide (PMA) treatment and either real time quantitative PCR (qPCR) or droplet digital PCR (ddPCR) to quantify a Lactobacillus rhamnosus and two Lactobacillus paracasei subsp. paracasei strains in piglet faeces. Adjustments of the PMA treatment conditions and reduction of the faecal sample size were necessary to obtain accurate discrimination between dead and live cells. The study also revealed differences of PMA efficiency among the two L. paracasei strains. Both PCR methods were able to specifically quantify each strain and provided comparable total bacterial counts. However, quantification of lower numbers of viable cells was best achieved with ddPCR, which was characterized by a reduced lower limit of quantification (improvement of up to 1.76 log 10 compared to qPCR). All three strains were able to survive in the piglets' gut with viability losses between 0.78 and 1.59 log 10 /g faeces. This study shows the applicability of PMA-ddPCR to specific quantification of small numbers of viable bacterial cells in the presence of an important background of unwanted microorganisms, and without the need to set up standard curves. It also illustrates the need to adapt PMA protocols according to the final matrix and target strain, even for closely related strains. The PMA-ddPCR approach provides a new tool to quantify bacterial survival in faecal samples from a preclinical and clinical trial. Copyright © 2018 The Authors. Published by

  3. First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta)

    International Nuclear Information System (INIS)

    Sanita di Toppi, L.; Pawlik-Skowronska, B.; Vurro, E.; Vattuone, Z.; Kalinowska, R.; Restivo, F.M.; Musetti, R.; Skowronski, T.

    2008-01-01

    'First line' defence mechanisms, such as phytochelatin biosynthesis, and 'second line' mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 μM Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 μM) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a 'second line' mechanism to counteract Cd stress, activated when there is a decline in the 'first line' mechanism of Cd detoxification given by phytochelatins. - Trebouxia impressa photobionts protect themselves against cadmium stress by means of phytochelatins and stress proteins

  4. First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta)

    Energy Technology Data Exchange (ETDEWEB)

    Sanita di Toppi, L. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy)], E-mail: luigi.sanitaditoppi@unipr.it; Pawlik-Skowronska, B. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Vurro, E. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Vattuone, Z. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Kalinowska, R. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Restivo, F.M. [Dipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Musetti, R. [Dipartimento di Biologia Applicata alla Difesa delle Piante, via delle Scienze 208, Universita di Udine, 33100 Udine (Italy); Skowronski, T. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland)

    2008-01-15

    'First line' defence mechanisms, such as phytochelatin biosynthesis, and 'second line' mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 {mu}M Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 {mu}M) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a 'second line' mechanism to counteract Cd stress, activated when there is a decline in the 'first line' mechanism of Cd detoxification given by phytochelatins. - Trebouxia impressa photobionts protect themselves against cadmium stress by means of phytochelatins and stress proteins.

  5. First on-line $\\beta$-NMR on oriented nuclei magnetic dipole moments of the $\

    CERN Document Server

    Giles, T; Stone, N J; Van Esbroeck, K; White, G; Wöhr, A; Veskovic, M; Towner, I S; Mantica, P F; Prisciandaro, J I; Morrissey, D J; Fedosseev, V; Mishin, V I; Köster, U; Walters, W B

    2000-01-01

    The first fully on-line use of the angular distribution of $\\beta$ - emission in detection of NMR of nuclei oriented at low temperatures is reported. The magnetic moments of the single valence particle, intermediate mass, isotopes $^{67}$Ni($\

  6. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.

    Directory of Open Access Journals (Sweden)

    Julie H Levison

    Full Text Available We investigated the prevalence of wild-type virus (no major drug resistance and drug resistance mutations at second-line antiretroviral treatment (ART failure in a large HIV treatment program in South Africa.HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%. Mean duration on ART (SD prior to initiation of second-line ART was 23 (17 months, and time from second-line ART initiation to failure was 10 (9 months. Plasma samples were obtained 7(9 months from confirmed failure. At second-line failure, 22 patients (67% had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5 months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

  7. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.

    Science.gov (United States)

    Zhang, Wei; Chen, Qi; Liang, Xiao; Liu, Wenzhong; Xiao, Shudong; Graham, David Y; Lu, Hong

    2015-11-01

    To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. NCT02175901. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Pretreatment long interspersed element (LINE-1 methylation levels, not early hypomethylation under treatment, predict hematological response to azacitidine in elderly patients with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Cross M

    2013-06-01

    Full Text Available Michael Cross,1 Enrica Bach,1 Thao Tran,1 Rainer Krahl,1 Nadja Jaekel,1 Dietger Niederwieser,1 Christian Junghanss,2 Georg Maschmeyer,3 Haifa Kathrin Al-Ali11Division of Hematology and Oncology, University of Leipzig, Leipzig, Germany; 2Clinic for Hematology, Oncology and Palliative Medicine, University of Rostock, Rostock, Germany; 3Clinic for Hematology, Oncology and Palliative Medicine, Ernst-von-Bergmann Clinic, Potsdam, GermanyBackground: Epigenetic modulations, including changes in DNA cytosine methylation, are implicated in the pathogenesis and progression of acute myeloid leukemia (AML. Azacitidine is a hypomethylating agent that is incorporated into RNA as well as DNA. Thus, there is a rationale to its use in patients with AML. We determined whether baseline and/or early changes in the methylation of long interspersed element (LINE-1 or CDH13 correlate with bone marrow blast clearance, hematological response, or survival in patients with AML treated with azacitidine.Methods: An open label, phase I/II trial was performed in 40 AML patients (median bone marrow blast count was 42% unfit for intensive chemotherapy treated with azacitidine 75 mg/m2/day subcutaneously for 5 days every 4 weeks. Bone marrow mononuclear cell samples were taken on day 0 (pretreatment and day 15 during the first treatment cycle; LINE-1 and CDH13 methylation levels were quantified by methylation-specific, semiquantitative, real-time polymerase chain reaction.Results: Treatment with azacitidine significantly reduced LINE-1 but not CDH13 methylation levels over the first cycle (P < 0.0001. Absolute LINE-1 methylation levels tended to be lower on day 0 (P = 0.06 and day 15 of cycle 1 (P = 0.03 in patients who went on to achieve subsequent complete remission, partial remission or hematological improvement versus patients with stable disease. However, the decrease in LINE-1 methylation over the first treatment cycle did not correlate with subsequent response (P = 0

  9. Ifosfamide and vinorelbine as first-line chemotherapy for metastatic breast cancer.

    Science.gov (United States)

    Leone, B A; Vallejo, C T; Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R

    1996-11-01

    To evaluate the efficacy and toxicity of the combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in metastatic breast cancer (MBC). Between August 1993 and August 1995, 45 patients with untreated MBC received a regimen that consisted of IFX 2 g/m2 by 1-hour intravenous (i.v.) infusion on days 1 to 3, mesna 400 mg/m2 by i.v. bolus at hours 0 and 4 and 800 mg/m2 orally at hour 8 on days 1 to 3, and VNB 35 mg/m2 by 20-minute i.v. infusion on days 1 and 15. Courses were repeated every 28 days. During the first course only, half-dose VNB (17.5 mg/m2) was administered on days 8 and 22. The median age was 53 years and 30 patients (67%) were postmenopausal. Dominant sites of disease were soft tissue in nine patients, bone in seven, and visceral in 29. Objective responses (ORs) were recorded in 25 of 43 assessable patients (58%; 95% confidence interval, 43% to 73%). Complete remissions (CRs) occurred in six patients (14%) and partial remissions (PRs) in 19 (44%). No change (NC) was recorded in 10 patients (23%) and progressive disease (PD) in eight patients (19%). The median time to treatment failure was 12 months and the median survival duration 19 months. Myelosuppression was the limiting toxicity, mainly leukopenia in 32 patients (74%). In contrast, anemia and thrombocytopenia were mild. Other significant toxicities included peripheral neuropathy in nine patients (21%), constipation in 15 (35%), and myalgias in 11 (26%). IFX/VNB is an active combination against MBC with moderate toxicity and deserves further evaluation.

  10. Review of the first line supervisory positions in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Mullin, D; Mackenzie, C W [Hickling Corp. (Canada)

    1995-10-01

    The authors review the nature of the tasks performed by first line maintenance supervisors in three nuclear power plants. They compare these tasks to core supervisory training curriculum, supervisory job descriptions, and both the process related to performance appraisals, and the criteria applied in carrying out these performance evaluations. Recommendations have been made concerning methods of increasing the relevancy of training and improving the performance appraisal process. ( author). 5 figs.

  11. Review of the first line supervisory positions in nuclear power plants

    International Nuclear Information System (INIS)

    Mullin, D.; Mackenzie, C.W.

    1995-10-01

    The authors review the nature of the tasks performed by first line maintenance supervisors in three nuclear power plants. They compare these tasks to core supervisory training curriculum, supervisory job descriptions, and both the process related to performance appraisals, and the criteria applied in carrying out these performance evaluations. Recommendations have been made concerning methods of increasing the relevancy of training and improving the performance appraisal process. ( author). 5 figs

  12. Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

    Science.gov (United States)

    Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

    2011-06-01

    First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

  13. Patient satisfaction with treatment in first-episode psychosis

    DEFF Research Database (Denmark)

    Haahr, Ulrik Helt; Simonsen, Erik; Røssberg, Jan Ivar

    2012-01-01

    Purpose: To examine first-episode psychotic patients' satisfaction with elements of a comprehensive 2-year treatment program. Subjects and method: The TIPS (Early Treatment and Intervention in Psychosis) project provided a 2-year treatment program consisting of milieu therapy (inpatient), individ......Purpose: To examine first-episode psychotic patients' satisfaction with elements of a comprehensive 2-year treatment program. Subjects and method: The TIPS (Early Treatment and Intervention in Psychosis) project provided a 2-year treatment program consisting of milieu therapy (inpatient......), individual psychotherapy, family intervention and medication. Of 140 patients at baseline, 112 were included at 2-year follow-up. Eighty-four participants were interviewed using a questionnaire eliciting levels of satisfaction with different treatment elements at two of the four sites. Results: Participants...... and non-participants did not differ on demographic or clinical data at baseline. Of those participating, 75% were satisfied with treatment in general. Individual and milieu therapy received higher rating than medication or family intervention. No predictors of general satisfaction with treatment were...

  14. CANINE ECTOPIC TREATMENT WITH FIRST MOLAR EXTRACTION

    Directory of Open Access Journals (Sweden)

    Angelica Margo

    2015-06-01

    Full Text Available Decision to extract or not and the type of tooth must be analyzed carefully in orthodontic treatment. Preferable tooth to be extracted was the tooth with large caries or restoration. Usually the type of tooth to be extracted was second molar (if the third molar appears, incisor, first molar, and combination of several teeth. Orthodontic treatment with molar extraction is more difficult to treat and the result is usually compromise. There are several considerations in extracting first molar such as tooth with large caries or restoration, hypoplasia, periapical disease, large discrepancy, high maxilla-mandibular plane angle, and cases with anterior open bite. Nowadays, orthodontic cases with molar extraction do not prolong the treatment time compared to premolar extraction case, but the anchorage system must be considered carefully. The present case was treated with extraction of first molar to solve anterior crowding with maximum anchorage at the upper jaw and using Nance Holding Appliance.

  15. An empirical evaluation of competency requirements for first-line managers to deal with resistance to change.

    OpenAIRE

    2007-01-01

    The point of departure of this study is that first-line managers play a pivotal role in the facilitation of change initiatives in organisations world-wide. Resistance to change is one of the primary reasons why change interventions fail or why success is not achieved in the change process. More specific, the inability of first-line managers to deal with resistance to change has been cited as a primary cause for change projects to fail. There is no evidence that any research has been conducted...

  16. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

    NARCIS (Netherlands)

    Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; Heuvel, M. van den; Ciuleanu, T.E.; Badin, F.; Ready, N.; Hiltermann, T.J.N.; Nair, S.; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J.M.; Rodriguez-Abreu, D.; Borghaei, H.; umenschein GR, J.r. Bl; Villaruz, L.C.; Havel, L.; Krejci, J.; rral Jaime, J. Co; Chang, H.; Geese, W.J.; Bhagavatheeswaran, P.; Chen, A.C.; Socinski, M.A.

    2017-01-01

    BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  17. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Carbone, D. P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M. M.; Ciuleanu, T. -E.; Badin, F.; Ready, N.; Hiltermann, T. J. N.; Nair, S; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J. M.; Rodriguez-Abreu, D.; Borghaei, H.; Blumenschein, G. R.; Villaruz, L. C.; Havel, L.; Krejci, J.; Corral Jaime, J.; Chang, C. -H.; Geese, W. J.; Bhagavatheeswaran, P.; Chen, Alexander C.; Socinski, M. A.

    2017-01-01

    BACKGROUND Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  18. Pathogenesis and Treatment of Sole Ulcers and White Line Disease.

    Science.gov (United States)

    Shearer, J K; van Amstel, Sarel R

    2017-07-01

    Sole ulcers and white line disease are 2 of the most common claw horn lesions in confined dairy cattle. Predisposing causes include unbalanced weight bearing, and metabolic, enzymatic, and hormonal changes. The white line serves as the junction between the sole and axial and abaxial wall. It is vulnerable to trauma and separation, permitting organic matter to become entrapped. Colonization contributes to retrograde movement of the infection to the solar and perioplic corium, where an abscess forms resulting in pain and lameness. Successful treatment requires an orthopedic foot block to the healthy claw and corrective trimming of the lesion. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Science.gov (United States)

    Vandenhende, Marie-Anne; Bellecave, Pantxika; Recordon-Pinson, Patricia; Reigadas, Sandrine; Bidet, Yannick; Bruyand, Mathias; Bonnet, Fabrice; Lazaro, Estibaliz; Neau, Didier; Fleury, Hervé; Dabis, François; Morlat, Philippe; Masquelier, Bernard

    2014-01-01

    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. 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. 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 (plow-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. 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.

  20. "And first he drew a line"

    DEFF Research Database (Denmark)

    Graham, Brian Russell

    At the end of “Night the Seventh” of Blake’s The Four Zoas, Blake’s Los, against a background of “furious war”, takes a stance and then performs an act which might seem powerless and quaint against such a backdrop: he draws a line, beginning work consisting of lines which Enitharmon, his companion......, tinctures, as it emerges. Placing this moment in the context of the poem’s epic struggle, this paper explores the reasons for Blake’s choice of image at this juncture in the “history”, thereby making a contribution to our understanding of the opposition between form and formlessness in the narrative....

  1. 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.

  2. Asouzu's Complementary Ontology as a Foundation for a Viable ...

    African Journals Online (AJOL)

    This paper on “Asouzu's Complementary Ontology as a foundation for a viable Ethic of the Environment”, posits that an ethic of the environment can be seen as viable if it considers the whole of reality as ontologically relevant. This point of view would free environmental ethics of anthropocentric bias and its attendant ...

  3. Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

    Science.gov (United States)

    Pearson, Edward; McGarry, Lisa; Gala, Smeet; Nieset, Christopher; Nanavaty, Merena; Mwamburi, Mkaya; Levy, Yair

    2016-04-01

    Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Peroral endoscopic myotomy is a viable option for failed surgical esophagocardiomyotomy instead of redo surgical Heller myotomy: a single center prospective study.

    Science.gov (United States)

    Onimaru, Manabu; Inoue, Haruhiro; Ikeda, Haruo; Yoshida, Akira; Santi, Esperanza Grace; Sato, Hiroki; Ito, Hiroaki; Maselli, Roberta; Kudo, Shin-ei

    2013-10-01

    Surgical Heller myotomy has high rates of successful long-term results, but failed cases still remain. Moreover, the treatment strategy in patients with surgical myotomy failure is controversial. Recently, peroral endscopic myotomy (POEM) was reported to be efficient and safe in primary treatment of achalasia. In this study, we aimed to evaluate the efficacy and safety of POEM for surgical myotomy failure as a rescue second-line treatment, and we discuss the treatment options adapted in achalasia recurrence. A total of 315 consecutive achalasia patients received POEM from September 2008 to December 2012 in our hospital. Eleven (3.5%) patients who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment from other hospitals were included in this study. Patient background, barium swallow studies, esophagogastroduodenoscopy (EGD), manometry, and symptom scores were prospectively evaluated. In principle, all patients in whom surgical myotomy failed received pneumatic balloon dilatation (PBD) as the first line "rescue" treatment, and only if PBD failed were patients considered for rescue POEM. The PBD alone was effective in 1 patient, and in the remaining 10 patients, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in lower esophageal sphincter (LES) resting pressures (22.1 ± 6.6 mmHg vs 10.9 ± 4.5 mmHg, p myotomy were excellent. Long-term results are awaited. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  5. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

    Science.gov (United States)

    Shi, Y K; Wang, L; Han, B H; Li, W; Yu, P; Liu, Y P; Ding, C M; Song, X; Ma, Z Y; Ren, X L; Feng, J F; Zhang, H L; Chen, G Y; Han, X H; Wu, N; Yao, C; Song, Y; Zhang, S C; Song, W; Liu, X Q; Zhao, S J; Lin, Y C; Ye, X Q; Li, K; Shu, Y Q; Ding, L M; Tan, F L; Sun, Y

    2017-10-01

    Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P icotinib group than in the chemotherapy group. First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population. © The Author

  6. The debate: Treatment after the first seizure - The CONTRA.

    Science.gov (United States)

    Steinhoff, Bernhard J

    2017-07-01

    In many instances antiepileptic drug (AED) treatment of epilepsy patients is sustained for a long time and is even a lifelong therapy. Chronic drug treatment naturally means the potential burden of adverse effects. The prognosis to remain seizure-free is good after a first seizure even without AEDs. Therefore one has to consider the possibility that freedom from seizures when AED treatment has been initiated after the first seizure may not in fact be the result of the AED treatment. On the other hand seizure-free patients without severe side effects most probably will not consider discontinuing AEDs. Therefore in these cases it will not be possible to discover whether AEDs are really necessary to maintain freedom from seizures. Furthermore it has been shown that the long-term prognosis is independent of whether AED treatment started after the first or a following seizure. Therefore in most instances AED treatment after a first seizure should be avoided. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Walker Mark S

    2012-06-01

    Full Text Available Abstract Background Bevacizumab (B and cetuximab (C are both approved for use in the treatment of metastatic colorectal cancer (mCRC in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O and who had completed ≥ 1 Patient Care Monitor (PCM surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B = reference. Results 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38. Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD = 12.6. Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI ± B or C (23.1% and FOLFOX ± B or C (22.5%. Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p’s  Conclusions Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C.

  8. Fate of viable but non-culturable Listeria monocytogenes in pig manure microcosms

    Directory of Open Access Journals (Sweden)

    Jeremy eDesneux

    2016-03-01

    Full Text Available The fate of two strains of L. monocytogenes and their ability to become viable but non-culturable (VBNC was investigated in microcosms containing piggery effluents (two raw manures and two biologically treated manures stored for two months at 8°C and 20°C. Levels of L. monocytogenes were estimated using the culture method, qPCR, and propidium monoazide treatment combined with qPCR (qPCRPMA. The chemical composition and the microbial community structure of the manures were also analysed. The strains showed similar decline rates and persisted up to 63 days. At day zero, the percentage of VBNC cells among viable cells was higher in raw manures (81.5-94.8% than in treated manures (67.8-79.2%. The changes in their proportion over time depended on the temperature and on the type of effluent: the biggest increase was observed in treated manures at 20°C and the smallest increase in raw manures at 8°C. The chemical parameters had no influence on the behaviour of the strains, but decrease of the persistence of viable cells was associated with an increase in the microbial richness of the manures. This study demonstrated that storing manure altered the culturability of L. monocytogenes, which rapidly entered the VBNC state, and underlines the importance of including VBNC cells when estimating the persistence of the pathogens in farm effluents.

  9. Advanced Design of the First Quasi-optical Transmission Line for ECRH at TJ-II

    International Nuclear Information System (INIS)

    Fernandez, A.; Likin, K.; Martin, R.

    1999-01-01

    TJ-II plasma start-up and heating are made by electron cyclotron resonance waves at the second harmonic of the electron cyclotron frequency. The microwave power of the gyrotrons is transmitted by two quasi-optical transmission lines. The first line launches the microwave power under fixed injection geometry, i. e. there is no a possibility to change the launching angle the wave polarization. Due to the long distance between the last focusing mirror and the center TJ-II vessel the beam is quite wide at plasma border. The second line has a moveable mirror installed inside the TJ-II vessel. To get high absorption efficiency and a narrow energy deposition profile the internal mirror focuses the wave beam at plasma center. The beam width is about 2 cm. To get more flexibility in experiments on heating and current drive the first transmission line needs to be upgraded. The designs is presented in this report. It includes and internal mirror to focus the beam and to change the injection angle. A polarizer consisting in two corrugated mirrors will be incorporated to get any wave polarization. Two mirrors with an array of coupling holes and calorimetric measurements of the energy absorbed in the barrier window will permit the estimation of the microwave power launched the TJ-II. (Author) 13 refs

  10. Primary stroke prevention and hypertension treatment: which is the first-line strategy?

    Science.gov (United States)

    Ravenni, Roberta; Jabre, Joe F; Casiglia, Edoardo; Mazza, Alberto

    2011-07-05

    Hypertension (HT) is considered the main classic vascular risk factor for stroke and the importance of lowering blood pressure (BP) is well established. However, not all the benefit of antihypertensive treatment is due to BP reduction per se, as the effect of reducing the risk of stroke differs among classes of antihypertensive agents. Extensive evidences support that angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), dihydropyridine calcium channel blockers (CCB) and thiazide diuretics each reduced risk of stroke compared with placebo or no treatment. Therefore, when combination therapy is required, a combination of these antihypertensive classes represents a logical approach. Despite the efficacy of antihypertensive therapy a large proportion of the population, still has undiagnosed or inadequately treated HT, and remain at high risk of stroke. In primary stroke prevention current guidelines recommend a systolic/diastolic BP goal of market of the fixed-dose combination (FDC) of ACEI or ARB and CCB should provide a better control of BP. However to confirm the efficacy of the FDC in primary stroke prevention, clinical intervention trials are needed.

  11. PMA-Linked Fluorescence for Rapid Detection of Viable Bacterial Endospores

    Science.gov (United States)

    LaDuc, Myron T.; Venkateswaran, Kasthuri; Mohapatra, Bidyut

    2012-01-01

    The most common approach for assessing the abundance of viable bacterial endospores is the culture-based plating method. However, culture-based approaches are heavily biased and oftentimes incompatible with upstream sample processing strategies, which make viable cells/spores uncultivable. This shortcoming highlights the need for rapid molecular diagnostic tools to assess more accurately the abundance of viable spacecraft-associated microbiota, perhaps most importantly bacterial endospores. Propidium monoazide (PMA) has received a great deal of attention due to its ability to differentiate live, viable bacterial cells from dead ones. PMA gains access to the DNA of dead cells through compromised membranes. Once inside the cell, it intercalates and eventually covalently bonds with the double-helix structures upon photoactivation with visible light. The covalently bound DNA is significantly altered, and unavailable to downstream molecular-based manipulations and analyses. Microbiological samples can be treated with appropriate concentrations of PMA and exposed to visible light prior to undergoing total genomic DNA extraction, resulting in an extract comprised solely of DNA arising from viable cells. This ability to extract DNA selectively from living cells is extremely powerful, and bears great relevance to many microbiological arenas.

  12. No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Si-wei Zhou

    Full Text Available The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR monoclonal antibodies (MAbs remains controversial in colorectal cancer (CRC. The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC through meta-analysis.Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO and European Society for Medical Oncology (ESMO were searched. Eligible studies were randomized controlled trials (RCTs which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS, progression-free survival (PFS, overall response rate (ORR and toxicities. Hazard ratios (HR and risk ratio (RR were used for the meta-analysis and were expressed with 95% confidence intervals.This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn't result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95 or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13. The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75 or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36. Patients who received combined therapy didn't have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]. Toxicities slightly increased in anti-EGFR drugs group.The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in

  13. Characterization of the Viable but Nonculturable (VBNC State in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Mohammad Salma

    Full Text Available The Viable But Non Culturable (VBNC state has been thoroughly studied in bacteria. In contrast, it has received much less attention in other microorganisms. However, it has been suggested that various yeast species occurring in wine may enter in VBNC following sulfite stress.In order to provide conclusive evidences for the existence of a VBNC state in yeast, the ability of Saccharomyces cerevisiae to enter into a VBNC state by applying sulfite stress was investigated. Viable populations were monitored by flow cytometry while culturable populations were followed by plating on culture medium. Twenty-four hours after the application of the stress, the comparison between the culturable population and the viable population demonstrated the presence of viable cells that were non culturable. In addition, removal of the stress by increasing the pH of the medium at different time intervals into the VBNC state allowed the VBNC S. cerevisiae cells to "resuscitate". The similarity between the cell cycle profiles of VBNC cells and cells exiting the VBNC state together with the generation rate of cells exiting VBNC state demonstrated the absence of cellular multiplication during the exit from the VBNC state. This provides evidence of a true VBNC state. To get further insight into the molecular mechanism pertaining to the VBNC state, we studied the involvement of the SSU1 gene, encoding a sulfite pump in S. cerevisiae. The physiological behavior of wild-type S. cerevisiae was compared to those of a recombinant strain overexpressing SSU1 and null Δssu1 mutant. Our results demonstrated that the SSU1 gene is only implicated in the first stages of sulfite resistance but not per se in the VBNC phenotype. Our study clearly demonstrated the existence of an SO2-induced VBNC state in S. cerevisiae and that the stress removal allows the "resuscitation" of VBNC cells during the VBNC state.

  14. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

    NARCIS (Netherlands)

    Homburg, R.R.; Hendriks, M.L.; König, T.E.; Anderson, R.A.; Balen, A.H.; Brincat, M.; Child, T.; Davies, M.; D'Hooghe, T.; Martinez, A; Rajkhowa, M.; Rueda-Saenz, R.; Hompes, P.G.A.; Lambalk, C.B.

    2012-01-01

    BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the

  15. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4 retrospective study

    Directory of Open Access Journals (Sweden)

    Danese Saverio

    2006-01-01

    Full Text Available Abstract Background Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. Methods 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial. All patients received carboplatin (AUC 5 plus paclitaxel (175 mg/m2 every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. Results 55 patients (46% did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54% had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23% referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months: 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77% had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%, between 2 and 6 months in 15 (25%, or after more than 6 months in 9 patients (15%. Considering all 120 treated patients

  16. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: The Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study

    International Nuclear Information System (INIS)

    Pignata, Sandro; Manzione, Luigi; Cartenì, Giacomo; Nardi, Mario; Danese, Saverio; Valerio, Maria Rosaria; Matteis, Andrea de; Massidda, Bruno; Gasparini, Giampietro; Di Maio, Massimo; Pisano, Carmela; De Placido, Sabino; Perrone, Francesco; Biamonte, Rosalbino; Scambia, Giovanni; Di Vagno, Giovanni; Colucci, Giuseppe; Febbraro, Antonio; Marinaccio, Marco; Vernaglia Lombardi, Alessandra

    2006-01-01

    Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m 2 ) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent

  17. Comparative effectiveness and safety of nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin in first-line treatment of advanced squamous cell non-small cell lung cancer in a US community oncology setting

    Directory of Open Access Journals (Sweden)

    Mudad R

    2017-10-01

    Full Text Available Raja Mudad,1 Manish B Patel,2 Sandra Margunato-Debay,2 David Garofalo,3 Lincy S Lal4 1University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Hollywood, FL, USA; 2Celgene Corporation, Summit, NJ, USA; 3Cardinal Health, Dallas, TX, USA; 4University of Texas School of Public Health, Houston, TX, USA Introduction: Real-world comparative effectiveness, safety, and supportive care use of nab-paclitaxel plus carboplatin vs gemcitabine plus platinum were analyzed in patients with advanced or metastatic squamous cell non-small cell lung cancer (NSCLC.Materials and methods: Patients who received ≥ 1 cycle of first-line nab-paclitaxel plus carboplatin or gemcitabine plus platinum were identified from the Navigating Cancer database. Clinical effectiveness endpoints included overall survival (OS and time to treatment discontinuation (TTD. Other endpoints included safety and utilization of supportive care. Cox proportional hazards models were used to control for potential confounding effects of baseline characteristics.Results: In total, 193 patients were included (nab-paclitaxel plus carboplatin, n = 61; gemcitabine plus platinum, n = 132. Baseline characteristics were generally similar between the cohorts. Patients receiving nab-paclitaxel plus carboplatin had a significantly longer OS than those receiving gemcitabine plus carboplatin (median, 12.8 vs 9.0 months; P = 0.03. However, the adjusted difference was not statistically significant (adjusted HR 1.55; 95% CI, 0.99–2.42; P = 0.06. nab-Paclitaxel plus carboplatin-treated patients had significantly longer TTD than gemcitabine plus carboplatin-treated patients (median, 4.3 vs 3.5 months; P = 0.03; adjusted HR 1.39; 95% CI, 1.01–1.90; P = 0.04. Grade 3 or 4 anemia and neutropenia were significantly lower in patients treated with nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin. Nausea and neuropathy (grade not specified were significantly higher in the

  18. Homeopathy - A Safe, Much Less Expensive, Non-Invasive, Viable Alternative for the Treatment of Patients Suffering from Loss of Lumbar Lordosis

    Directory of Open Access Journals (Sweden)

    Saiful Haque

    2016-12-01

    Full Text Available Objectives: Loss of lumbar lordosis causing pain and curvature of the vertebral skeleton to one side is a relatively uncommon disease. To our knowledge, successful treatment of loss of lumbar lordosis with any potentized homeopathic drug diluted above Avogadro’s limit (that is, above a potency of 12C has not been documented so far. In this communication, we intend to document a relatively rare case of loss of lumbar lordosis with osteophytic lippings, disc desiccation, and protrusion, causing a narrowing of secondary spinal canal and a bilateral neural foramina, leading to vertebral column curvature with acute pain in an adolescent boy. Methods: The patient had undergone treatment with orthodox Western medicines, but did not get any relief from, or cure of, the ailment; finally, surgery was recommended. The patient’s family brought the patient to the Khuda-Bukhsh Homeopathic Benevolent Foundation where a charitable clinic is run every Friday with the active participation of four qualified homeopathic doctors. A holistic method of homeopathic treatment was adopted by taking into consideration all symptoms and selecting the proper remedy by consulting the homeopathic repertory, mainly of Kent. Results: The symptoms were effectively treated with different potencies of a single homeopathic drug, Calcarea phos. X-ray and magnetic resonance imaging (MRI supported recovery and a change in the skeletal curvature that was accompanied by removal of pain and other acute symptoms of the ailment. Conclusion: Homeopathy can be a safe, much less expensive, non-invasive, and viable alternative for the treatment of such cases.

  19. PENGARUH PSYCHOLOGICAL EMPOWERMENT, EMPOWERING LEADERSHIP, SISTEM PENGUKURAN KINERJA PADA MOTIVASI INTRINSIK FIRST-LINE EMPLOYEES PERBANKAN

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Purnamawati

    2016-10-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui pengaruh Psychological Empowerment, Empowering Leadership, dan Sistem Pengukuran Kinerja Pada Motivasi Intrinsik First-Line Employees Perbankan. Penelitian ini adalah penelitian kuantitatif. Data yang digunakan adalah data primer berupa kuesioner yang menggunakan skala likert 1-5 dan terdiri atas 36 item pertanyaan. Responden pada penelitian ini adalah manajemen lini garis pertama pada sektor perbankan yaitu sejumlah 35 orang yang berasal dari 7 BPR yang ada di Kabupaten Buleleng. Metode analisis data menggunakan model regresi linear berganda dengan bantuan alat statistik SPSS. Hasil penelitian menunjukkan bahwa  Psychological Empowerment, Empowering Leadership, dan Sistem Pengukuran Kinerja berpengaruh positif dan signifikan pada Motivasi Intrinsik First-Line Employees Perbankan dengan menggunakan taraf signifikansi 5%.

  20. Delay to first treatment contact for alcohol use disorder.

    Science.gov (United States)

    Chapman, Cath; Slade, Tim; Hunt, Caroline; Teesson, Maree

    2015-02-01

    This study explored the patterns and correlates of time to first treatment contact among people with alcohol use disorder (AUD) in Australia. Specifically it examined the relationship between sex, birth cohort, onset of AUD symptoms, severity, comorbidity, symptom type and time to first treatment contact (treatment delay) among those with alcohol abuse and dependence in a large population sample. Data came from the 2007 Australian National Survey of Mental Health and Wellbeing (N=8841). A modified version of the World Health Organization's Composite International Diagnostic Interview was used to determine the presence and age of onset of DSM-IV AUD and other mental disorders and the age at which respondents first sought treatment for alcohol or other drug-related problems. Median time to first treatment contact for an AUD was 18 years (14 years dependence, 23 years abuse). Projected lifetime treatment rates were 78.1% for alcohol dependence and 27.5% for abuse. Those with earlier onset and from older cohorts reported longer delay and were less likely to ever seek treatment compared to those with later onset or from more recent cohorts. Those with comorbid anxiety but not mood disorder, or who reported alcohol-related role disruption or recurrent interpersonal problems were more likely to ever seek treatment and reported shorter delay compared to those who did not report these symptoms. Treatment delay for alcohol use disorder in Australia is substantial. Those with earlier onset and those with comorbid mood disorder should be a target for earlier treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study.

    Science.gov (United States)

    Cuneo, Antonio; Follows, George; Rigolin, Gian Matteo; Piciocchi, Alfonso; Tedeschi, Alessandra; Trentin, Livio; Medina Perez, Angeles; Coscia, Marta; Laurenti, Luca; Musuraca, Gerardo; Farina, Lucia; Rivas Delgado, Alfredo; Orlandi, Ester Maria; Galieni, Piero; Mauro, Francesca Romana; Visco, Carlo; Amendola, Angela; Billio, Atto; Marasca, Roberto; Chiarenza, Annalisa; Meneghini, Vittorio; Ilariucci, Fiorella; Marchetti, Monia; Molica, Stefano; Re, Francesca; Gaidano, Gianluca; Gonzalez, Marcos; Forconi, Francesco; Ciolli, Stefania; Cortelezzi, Agostino; Montillo, Marco; Smolej, Lukas; Schuh, Anna; Eyre, Toby A; Kennedy, Ben; Bowles, Kris M; Vignetti, Marco; de la Serna, Javier; Moreno, Carol; Foà, Robin; Ghia, Paolo

    2018-04-19

    We performed an observational study on the efficacy of bendamustine and rituximab as first salvage regimen in chronic lymphocytic leukemia. In an intention-to-treat analysis including 237 patients, the median progression free survival was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter progression free survival at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival was 74.5 months. Advanced Binet stage (i.e. III-IV or C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within named patient programs in the United Kingdom and in Italy was carried out with overall survival as objective endpoint. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, the overall survival did not differ between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in chronic lymphocytic leukemia in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of overall survival when used as first salvage treatment in patients without 17p deletion. ClinicalTrials.gov identifier: NCT02491398. Copyright © 2018, Ferrata Storti Foundation.

  2. Shortened first-line TB treatment in Brazil: potential cost savings for patients and health services

    NARCIS (Netherlands)

    Trajman, Anete; Bastos, Mayara Lisboa; Belo, Marcia; Calaça, Janaína; Gaspar, Júlia; Dos Santos, Alexandre Martins; Dos Santos, Camila Martins; Brito, Raquel Trindade; Wells, William A.; Cobelens, Frank G.; Vassall, Anna; Gomez, Gabriela B.

    2016-01-01

    Shortened treatment regimens for tuberculosis are under development to improve treatment outcomes and reduce costs. We estimated potential savings from a societal perspective in Brazil following the introduction of a hypothetical four-month regimen for tuberculosis treatment. Data were gathered in

  3. The Effects of First-Line Anti-Tuberculosis Drugs on the Actions of Vitamin D in Human Macrophages.

    Science.gov (United States)

    Chesdachai, Supavit; Zughaier, Susu M; Hao, Li; Kempker, Russell R; Blumberg, Henry M; Ziegler, Thomas R; Tangpricha, Vin

    2016-12-01

    Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH) 2 D 3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D 3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.

  4. Second line drug susceptibility testing to inform the treatment of rifampin-resistant tuberculosis: a quantitative perspective

    Directory of Open Access Journals (Sweden)

    Emily A. Kendall

    2017-03-01

    Full Text Available Treatment failure and resistance amplification are common among patients with rifampin-resistant tuberculosis (TB. Drug susceptibility testing (DST for second-line drugs is recommended for these patients, but logistical difficulties have impeded widespread implementation of second-line DST in many settings. To provide a quantitative perspective on the decision to scale up second-line DST, we synthesize literature on the prevalence of second-line drug resistance, the expected clinical and epidemiologic benefits of using second-line DST to ensure that patients with rifampin-resistant TB receive effective regimens, and the costs of implementing (or not implementing second-line DST for all individuals diagnosed with rifampin-resistant TB. We conclude that, in most settings, second-line DST could substantially improve treatment outcomes for patients with rifampin-resistant TB, reduce transmission of drug-resistant TB, prevent amplification of drug resistance, and be affordable or even cost-saving. Given the large investment made in each patient treated for rifampin-resistant TB, these payoffs would come at relatively small incremental cost. These anticipated benefits likely justify addressing the real challenges faced in implementing second-line DST in most high-burden settings.

  5. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    International Nuclear Information System (INIS)

    Griffiths, R. I.; Gleeson, M. L.; Danese, M. D.; Griffiths, R. I.; Mikhael, J.

    2012-01-01

    Rituximab improves survival in follicular lymphoma (FL), but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER) registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P)) or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years), 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI) $9,302-$28,643) and longer adjusted cumulative survival (0.18 years; 95% CI 0.10-0.27) over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531-296,337) per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

  6. MicroRNAs-449a and -449b exhibit tumor suppressive effects in retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Alissa [Division of Hematology, Oncology, and Stem Cell Transplantation, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611 (United States); Jones, Aunica [Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611 (United States); Bryar, Paul J. [Departments of Ophthalmology and Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Mets, Marilyn [Division of Ophthalmology, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611 (United States); Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611 (United States); Weinstein, Joanna [Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611 (United States); Division of Hematology, Oncology, and Stem Cell Transplantation, Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611 (United States); Zhang, Gang [Biostatistics Research Core, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611 (United States); Laurie, Nikia A., E-mail: n-laurie@northwestern.edu [Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, Chicago, IL 60611 (United States); Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611 (United States)

    2013-11-01

    Highlights: •We validate miR-449a/b expression in primary human retinoblastomas and cell lines. •Exogenous miRs-449a/b inhibited proliferation in retinoblastoma cell lines. •Exogenous miRs-449a/b increased apoptosis in retinoblastoma cell lines. •miRs-449a/b could serve as viable therapeutic targets for retinoblastoma treatment. -- Abstract: Retinoblastoma is the most common pediatric cancer of the eye. Currently, the chemotherapeutic treatments for retinoblastoma are broad-based drugs such as vincristine, carboplatin, or etoposide. However, therapies targeted directly to aberrant signaling pathways may provide more effective therapy for this disease. The purpose of our study is to illustrate the relationship between the expressions of miRs-449a and -449b to retinoblastoma proliferation and apoptosis. We are the first to confirm an inhibitory effect of miR-449a and -449b in retinoblastoma by demonstrating significantly impaired proliferation and increased apoptosis of tumor cells when these miRNAs are overexpressed. This study suggests that these miRNAs could serve as viable therapeutic targets for retinoblastoma treatment.

  7. Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral therapy or receiving a first-line treatment.

    Science.gov (United States)

    Calza, Leonardo; Colangeli, Vincenzo; Magistrelli, Eleonora; Rossi, Nicolo'; Rosselli Del Turco, Elena; Bussini, Linda; Borderi, Marco; Viale, Pierluigi

    2017-05-01

    The combination antiretroviral therapy (cART) has dramatically improved the life expectancy of patients with HIV infection, but may lead to several long-term metabolic abnormalities. However, data about the frequency of metabolic syndrome (MS) in HIV-infected people vary considerably across different observational studies. The prevalence of MS among HIV-infected patients was evaluated by a cross-sectional study conducted among subjects naive to cART or receiving the first antiretroviral regimen and referring to our Clinics from January 2015 to December 2015. The diagnosis of MS was made based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. The study recruited 586 patients: 98 naive to cART and 488 under the first antiretroviral treatment. The prevalence of MS, according to NCEP-ATP III criteria, was significantly higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014). The most frequently reported components of MS among treated patients were high triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and hypertension (19.7%). On multivariate analysis, long duration of HIV infection, low nadir of CD4 lymphocytes, high body mass index, current use of one protease inhibitor, and long duration of cART were significantly associated with a higher risk of MS, while current use of one integrase inhibitor was significantly associated with a lower risk of MS. The non-negligible prevalence of MS among HIV-infected patients under cART requires a careful and periodic monitoring of its components, with particular attention to dyslipidemia and hypertension.

  8. 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.

  9. A factor converting viable but nonculturable Vibrio cholerae to a culturable state in eukaryotic cells is a human catalase.

    Science.gov (United States)

    Senoh, Mitsutoshi; Hamabata, Takashi; Takeda, Yoshifumi

    2015-08-01

    In our previous work, we demonstrated that viable but nonculturable (VBNC) Vibrio cholerae O1 and O139 were converted to culturable by coculture with eukaryotic cells. Furthermore, we isolated a factor converting VBNC V. cholerae to culturable (FCVC) from a eukaryotic cell line, HT-29. In this study, we purified FCVC by successive column chromatographies comprising UNO Q-6 anion exchange, Bio-Scale CHT2-1 hydroxyapatite, and Superdex 200 10/300 GL. Homogeneity of the purified FCVC was demonstrated by SDS-PAGE. Nano-LC MS/MS analysis showed that the purified FCVC was a human catalase. An experiment of RNAi knockdown of catalase mRNA from HT-29 cells and treatment of the purified FCVC with a catalase inhibitor, 3-amino-1,2,4-triazole confirmed that the FCVC was a catalase. A possible role of the catalase in converting a VBNC V. cholerae to a culturable state in the human intestine is discussed. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  10. 46 CFR 197.454 - First aid and treatment equipment.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false First aid and treatment equipment. 197.454 Section 197.454 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND... Equipment § 197.454 First aid and treatment equipment. The diving supervisor shall ensure that medical kits...

  11. Operative shortening of the sling as a second-line treatment after TVT failure

    Science.gov (United States)

    Matuszewski, Marcin; Michajłowski, Jerzy; Krajka, Kazimierz

    2011-01-01

    Introduction Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during physical exertion, sneezing, coughing, laughing, or other activities that put pressure on the bladder. In some cases, recurrent or persistent SUI after sling operations may be caused by too loose placement of the sling. In the current study, we describe our method of shortening of the sling as a second-line treatment of tension-free vaginal tape (TVT) failure. Materials and methods Four women, aged 46-61, after initial TVT operation were treated for persistent SUI. The severity of SUI was estimated by: physical examinations, cough tests, 24-h pad tests, and King's Health Questionnaire. The shortening procedure, based on excising the fragment of tape and suturing it back, was performed in all patients. Results All cases achieved a good result, which was defined as restoration of full continence. No complications occurred. The 12-month follow-up showed no side-effects. The postoperative control tests: the cough and 24-h pad tests were negative in all women. The general health perceptions increased after the shortening procedure by a mean value 44.25%. The incontinence impact decreased by a mean value 44.6%. In all patients, role and physical limitations significantly decreased (by 88.5% and 80.5%, respectively). The negative emotions connected with SUI significantly decreased after the second procedure. Conclusions The operative shortening of the implanted sling is a simple, cheap, and effective method of second-line treatment in cases of TVT failure and may be offered to the majority of patients with insufficient urethral support after the first procedure. PMID:24578885

  12. Clinical decision-making and health-related quality of life during first-line and maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC): findings from a real-world setting.

    Science.gov (United States)

    Sztankay, Monika; Giesinger, Johannes Maria; Zabernigg, August; Krempler, Elisabeth; Pall, Georg; Hilbe, Wolfgang; Burghuber, Otto; Hochmair, Maximilian; Rumpold, Gerhard; Doering, Stephan; Holzner, Bernhard

    2017-08-23

    Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT. Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients' and physicians' reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models. Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p loss (p = 0.043), constipation (p = 0.017) and chest pain (p = 0.022), and a deterioration in emotional functioning (p = 0.023) and cognitive functioning (p = 0.044) during MT. Our results indicate that HRQOL and symptom burden improve between first-line treatment to MT in some respects, although some late toxicity persists. Discrepancies between patients' and physicians

  13. Mobilization of peripheral blood stem cells in CLL patients after front-line fludarabine treatment.

    Science.gov (United States)

    Lysak, D; Koza, V; Steinerova, K; Jindra, P; Vozobulova, V; Schutzova, M

    2005-07-01

    Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.

  14. Should laparoscopy and dye test be a first line evaluation for infertile women in southeast Nigeria?

    Science.gov (United States)

    Ikechebelu, J I; Mbamara, S U

    2011-01-01

    Laparoscopy and dye test is an important investigation in the evaluation of infertile women which has been underutilised in our practice. This review is aimed at determining whether the findings of this procedure are substantial enough to make it a first line evaluation for infertile women. A review of the laparoscopic findings in infertile women who presented for evaluation and treatment at a private fertility centre was carried out. A total of 253 day-case laparoscopy and dye test procedures were reviewed, 115 (45.0%) were done for primary infertility, 137 (54.5%) for secondary infertility and 1 (0.4%) for primary amenorrhoea and infertility. The mean period of infertility was 4.5 years with a range of 2-10 years and the women were aged between 19 and 52 years. Analysis of the result showed that 100 (39.5%) women had normal patent tubes while 153 (60.4%) had tubal pathologies like bilateral tubal occlusion in 97 (38.3%) and unilateral tubal occlusion in 56 (22.1%) women. Pelvic adhesion of varying degrees of severity was present in 108 (42.7%) women. Bilateral tubal occlusion was more common in nulliparous women and those aged between 30-39 years. One or both ovaries were normal (functional) in 189 (74.7%) women. Altogether, only 43 (17.0%) women were "normal" (had patent tubes, functional ovary and no pelvic adhesion). Additional pelvic pathology was present in 142 (56.1%) women. The commonest was uterine fibroid (leiomyomata) of various sizes in 100 (39.5%) of the women, followed by ovarian cyst in 56 (22.2%) and endometriosis in 11 (4.4%) women. Other pathologies observed include uterine abnormalities and unruptured ectopic pregnancy. Only 16 (37.2%) of the 43 "normal" women had no additional pelvic pathology. The high prevalence o tuboperitoneal factor and additional pelvic pathology in these infertile women reveal the importance of laparoscopic evaluation. We recommend the use of laparoscopy and dye test as a first line investigation in our environment to

  15. Cost-effectiveness analysis of EGFR mutation testing and gefitinib as first-line therapy for non-small cell lung cancer.

    Science.gov (United States)

    Narita, Yusuke; Matsushima, Yukiko; Shiroiwa, Takeru; Chiba, Koji; Nakanishi, Yoichi; Kurokawa, Tatsuo; Urushihara, Hisashi

    2015-10-01

    The combination use of gefitinib and epidermal growth factor receptor (EGFR) testing is a standard first-line therapy for patients with non-small cell lung cancer (NSCLC). Here, we examined the cost-effectiveness of this approach in Japan. Our analysis compared the 'EGFR testing strategy', in which EGFR mutation testing was performed before treatment and patients with EGFR mutations received gefitinib while those without mutations received standard chemotherapy, to the 'no-testing strategy,' in which genetic testing was not conducted and all patients were treated with standard chemotherapy. A three-state Markov model was constructed to predict expected costs and outcomes for each strategy. We included only direct medical costs from the healthcare payer's perspective. Outcomes in the model were based on those reported in the Iressa Pan-Asia Study (IPASS). The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted life-years (QALYs) gained. Sensitivity and scenario analyses were conducted. The incremental cost and effectiveness per patient of the 'EGFR testing strategy' compared to the 'no-testing strategy' was estimated to be approximately JP¥122,000 (US$1180; US$1=JP¥104 as of February 2014) and 0.036 QALYs. The ICER was then calculated to be around JP¥3.38 million (US$32,500) per QALY gained. These results suggest that the 'EGFR testing strategy' is cost-effective compared with the 'no-testing strategy' when JP¥5.0 million to 6.0 million per QALY gained is considered an acceptable threshold. These results were supported by the sensitivity and scenario analyses. The combination use of gefitinib and EGFR testing can be considered a cost-effective first-line therapy compared to chemotherapy such as carboplatin-paclitaxel for the treatment for NSCLC in Japan. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. The thermospheric auroral red line polarization: confirmation of detection and first quantitative analysis

    Directory of Open Access Journals (Sweden)

    Moen Joran

    2013-01-01

    Full Text Available The thermospheric atomic oxygen red line is among the brightest in the auroral spectrum. Previous observations in Longyearbyen, Svalbard, indicated that it may be intrinsically polarized, but a possible contamination by light pollution could not be ruled out. During the winter 2010/2011, the polarization of the red line was measured for the first time at the Polish Hornsund polar base without contamination. Two methods of data analysis are presented to compute the degree of linear polarization (DoLP and angle of linear polarization (AoLP: one is based on averaging and the other one on filtering. Results are compared and are in qualitative agreement. For solar zenith angles (SZA larger than 108° (with no contribution from Rayleigh scattering, the DoLP ranges between 2 and 7%. The AoLP is more or less aligned with the direction of the magnetic field line, in agreement with the theoretical predictions of Bommier et al. (2010. However, the AoLP values range between ±20° around this direction, depending on the auroral conditions. Correlations between the polarization parameters and the red line intensity I were considered. The DoLP decreases when I increases, confirming a trend observed during the observations in Longyearbyen. However, for small values of I, DoLP varies within a large range of values, while for large values of I, DoLP is always small. The AoLP also varies with the red line intensity, slightly rotating around the magnetic field line.

  17. Integrated electrochemical sensor array for on-line monitoring of yeast fermentations

    NARCIS (Netherlands)

    Krommenhoek, E.E.; Gardeniers, Johannes G.E.; Bomer, Johan G.; Li, X.; Ottens, M.; van Dedem, G.W.K.; van Leeuwen, M.; van Gulik, W.M.; van der Wielen, L.A.M.; Heijnen, J.J.; van den Berg, Albert

    2007-01-01

    This paper describes the design, modeling, and experimental characterization of an electrochemical sensor array for on-line monitoring of fermentor conditions in both miniaturized cell assays and in industrial scale fertnentations. The viable biomass concentration is determined from impedance

  18. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  19. Lower LINE-1 methylation in first-episode schizophrenia patients with the history of childhood trauma.

    Science.gov (United States)

    Misiak, Błażej; Szmida, Elżbieta; Karpiński, Paweł; Loska, Olga; Sąsiadek, Maria M; Frydecka, Dorota

    2015-01-01

    We investigated methylation of DNA repetitive sequences (LINE-1 and BAGE) in peripheral blood leukocytes from first-episode schizophrenia (FES) patients and healthy controls (HCs) with respect to childhood adversities. Patients were divided into two subgroups based on the history of childhood trauma - FES(+) and FES(-) subjects. The majority of HCs had a negative history of childhood trauma - HCs(-) subjects. FES(+) patients had significantly lower LINE-1 methylation in comparison with FES(-) patients or HC(-) subjects. Emotional abuse and total trauma score predicted lower LINE-1 methylation in FES patients, while general trauma score was associated with lower BAGE methylation in HCs. Childhood adversities might be associated with global DNA hypomethylation in adult FES patients.

  20. Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

    Science.gov (United States)

    Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

    2017-09-01

    This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.

  1. Diagnosis and first-line treatment of breast cancer in Italian general hospitals

    International Nuclear Information System (INIS)

    Interdisciplinary Group for Cancer Care Evaluation, Milan

    1986-01-01

    The quality of the diagnostic and therapeutic process of 1262 newly diagnosed breast cancer patients was evaluated in 63 Italian general hospital over the period March 1983 - April 1984. Most of the patients (91%) discovered their own lesion, which was a nodule in 83% of the cases. Practice of breast self examination was reported by 418 (33%) patients, only 28% of whom did that on a regular monthly basis. A diagnostic delay>3 months was present in 36% of the patients. Among the preoperative work-up examinations, skeletal X-ray or bone scan was not performed in 20% of patients, whereas other essential examinations were done in most. The Patey type of radical mastectomy was the most frequent surgical procedure; quadrantectomy was performed in only 26% of eligible patients, more frequently in younger (34%) than in older patients (21%). Adjuvant chemotherapy was recommended for 11% and 6% of pre- and postmenopausal N- patients, and for 78% and 47% of pre- and postmenopausal N+ patients. Forty-three of the 63 participating hospitals reported they adhered to the guidelines defined by the Italian Breast Cancer Task Force (F.O.N.Ca.M.) but this was not associated with substantial evidence of better quality of care. Similary, no associations emerged between several hospitals' organizational features and adherence to recommended treatment guidelines. The study is ongoing to assess the quality of postsurgical treatment and to measure its impact on patients' survival

  2. First Detections of the [NII] 122 Micrometer Line at High Redshift: Demonstrating the Utility of the Line for Studying Galaxies in the Early Universe

    Science.gov (United States)

    Ferkinhoff, Carl; Brisbin, Drew; Nikola, Thomas; Parshley, Stephen C.; Stacey, Gordon J.; Phillips, Thomas G.; Falgarone, Edith; Benford, Dominic J.; Staguhn, Johannes G.; Tucker, Carol E.

    2011-01-01

    We report the first detections of the [NIl] 122 {\\mu} m line from a high redshift galaxy. The line was strongly (> 6{\\sigma}) detected from SMMJ02399-0136, and HI413+ 117 (the Cloverleaf QSO) using the Redshift(z) and Early Universe Spectrometer (ZEUS) on the CSO. The lines from both sources are quite bright with line-to-FIR continuum luminosity ratios that are approx.7.0x10(exp -4) (Cloverleaf) and 2.1x10(exp -3) (SMMJ02399). With ratios 2-10 times larger than the average value for nearby galaxies, neither source exhibits the line-to-continuum deficits seen in nearby sources. The line strengths also indicate large ionized gas fractions, approx.8 to 17% of the molecular gas mass. The [OIII]/[NII] line ratio is very sensitive to the effective temperature of ionizing stars and the ionization parameter for emission arising in the narrow-line region (NLR) of an AGN. Using our previous detection of the [01II] 88 {\\mu}m line, the [OIII]/ [NIl] line ratio for SMMJ02399-0136 indicates the dominant source of the line emission is either stellar HII regions ionized by 09.5 stars, or the NLR of the AGN with ionization parameter 10g(U) = -3.3 to -4.0. A composite system, where 30 to 50% of the FIR lines arise in the NLR also matches the data. The Cloverleaf is best modeled by a superposition of approx.200 M82like starbursts accounting for all of the FIR emission and 43% of the [NIl] line. The remainder may come from the NLR. This work demonstrates the utility of the [NIl] and [OIII] lines in constraining properties of the ionized medium.

  3. Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

    Directory of Open Access Journals (Sweden)

    Schuette Wolfgang

    2012-01-01

    Full Text Available Abstract Background Second-line treatment of advanced non-small-cell lung cancer (NSCLC improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS and health-related quality of life (HR-QoL during second-line pemetrexed treatment in routine clinical practice. Methods Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI of ≥ 10% (absolute or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response". HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D. Factors potentially associated with KI benefit response were evaluated using logistic regression models. Results Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%, 471 (90.4% completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2% achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%. Conclusions In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years, physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Trial registration Registered on ClinicalTrials.gov (NCT00540241 on October 4, 2007

  4. Neurostimulation in cluster headache

    DEFF Research Database (Denmark)

    Pedersen, Jeppe L; Barloese, Mads; Jensen, Rigmor H

    2013-01-01

    PURPOSE OF REVIEW: Neurostimulation has emerged as a viable treatment for intractable chronic cluster headache. Several therapeutic strategies are being investigated including stimulation of the hypothalamus, occipital nerves and sphenopalatine ganglion. The aim of this review is to provide...... effective strategy must be preferred as first-line therapy for intractable chronic cluster headache....

  5. 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.

  6. Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Höhler Thomas

    2004-07-01

    Full Text Available Abstract Background Combination therapy of irinotecan, folinic acid (FA and 5-fluorouracil (5-FU has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. Methods A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2, L-FA (200 mg/m2 and 5-FU bolus (400 mg/m2 on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2. One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. Results The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%. Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%, nausea/vomiting (12%, leucopenia (3%, neutropenia (9% and mucositis (3%. The overall response rate was 31% (4 CR and 7 PR, with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. Conclusions The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant

  7. Viable Intrauterine Pregnancy and Coexisting Molar Pregnancy in a Bicornuate Uterus: A Rare Presentation

    Directory of Open Access Journals (Sweden)

    Kavitha Krishnamoorthy

    2016-01-01

    Full Text Available A complete hydatidiform mole with a viable coexisting fetus (CMCF is a rare occurrence. Similarly, Mullerian anomalies such as a bicornuate uterus are uncommon variants of normal anatomy. We report a case of a 40-year-old female with a known bicornuate uterus presenting at 13 weeks gestation with vaginal bleeding. Ultrasound findings showed a healthy viable pregnancy in the right horn with complete molar pregnancy in the left horn. After extensive counseling, the patient desired conservative management, however, was unable to continue due to profuse vaginal bleeding. The patient underwent suction dilation and curettage under general anesthesia and evacuation of the uterine horns. Postoperatively, the patient was followed until serum beta-human chorionic gonadotropin (β-hCG level dropped to <5 mU. This is the first case of a CMCF reported in a bicornuate uterus, diagnosed with the use of ultrasound imaging.

  8. Rocuronium Versus Suxamethonium: A Survey of First-line Muscle Relaxant Use in UK Prehospital Rapid Sequence Induction.

    Science.gov (United States)

    Hartley, Emma L; Alcock, Roger

    2015-04-01

    Prehospital anaesthesia in the United Kingdom (UK) is provided by Helicopter Emergency Medical Service (HEMS) and British Association for Immediate Care (BASICS), a road-based service. Muscle relaxation in rapid sequence induction (RSI) has been traditionally undertaken with the use of suxamethonium; however, rocuronium at higher doses has comparable intubating conditions with fewer side effects. The aim of this survey was to establish how many prehospital services in the UK are now using rocuronium as first line in RSI. An online survey was constructed identifying choice of first-line muscle relaxant for RSI and emailed to lead clinicians for BASICS and HEMS services across the UK. If rocuronium was used, further questions regarding optimal dose, sugammadex, contraindications, and difference in intubating conditions were asked. A total of 29 full responses (93.5%) were obtained from 31 services contacted. Suxamethonium was used first line by 17 prehospital services (58.6%) and rocuronium by 12 (41.4%). In 11 services (91.7%), a dose of 1 mg/kg of rocuronium was used, and in one service, 1.2 mg/kg (8.3%) was used. No services using rocuronium carried sugammadex. In five services, slower relaxation time was found using rocuronium (41.7%), and in seven services, no difference in intubation conditions were noted (58.3%). Contraindications to rocuronium use included high probability of difficult airway and anaphylaxis. Use of rocuronium as first-line muscle relaxant in prehospital RSI is increasing. Continued auditing of practice will ascertain which services have adopted change and identify if complications of failed intubation increase as a result.

  9. Renal Artery Embolization - A First Line Treatment Option For End-Stage Hydronephrosis

    International Nuclear Information System (INIS)

    Mitra, Kakali; Prabhudesai, Vikramaditya; James, R. Lester; Jones, Robert W. A.; French, Michael E.; Cowling, Mark; West, David J.

    2004-01-01

    Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic. In our unit, patients are offered renal artery embolization as an alternative treatment option. Patients and Methods: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20-51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function. Mean follow-up was 64.13 weeks (range 14-200). All patients had loin pain and hydronephrosis. Twelve patients had primary pelvi-ureteric junction obstruction (PUJO). Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction. One patient had chronic pain in an obstructed but reasonably functioning kidney following a previous pyeloplasty for PUJO which demanded intervention. Mean split function on renography was 11% (range 0-46%). Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles.Results: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis. One patient required readmission with this condition. One patient developed a hematoma at the puncture site. Mean hospital stay was 2.3 days. Fourteen patients are happy with the result and are completely pain free. One patient has minor discomfort but is delighted with the result. Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis. Conclusion: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy

  10. Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST).

    Science.gov (United States)

    Nigrovic, Peter A; Beukelman, Timothy; Tomlinson, George; Feldman, Brian M; Schanberg, Laura E; Kimura, Yukiko

    2018-03-01

    confounding. With 200 patients in a 2:1 ratio of biologic to non-biologic, there is a >90% probability of finding biologic consensus treatment plans more effective if the rate of clinically inactive disease is 30% higher than for non-biologic therapy. Additional outcomes include Patient-Reported Outcomes Measurement Information System measures and other parent-/patient-reported outcomes reported in real time using smartphone technology. Routine operation of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry will allow assessment of outcomes over at least 10 years. FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) began enrollment in November 2016. The observational design may not provide balance in measured and unmeasured confounders. Use of consensus treatment plan (CTP) strategies at frequencies more unbalanced than predicted could reduce the chance of finding differences in efficacy. FiRst-Line Options for Systemic juvenile idiopathic arthritis Treatment (FROST) will provide the first prospective comparison of Childhood Arthritis and Rheumatology Research Alliance's (CARRA's) consensus-derived non-biologic versus biologic management strategies in systemic juvenile idiopathic arthritis, performed in a real-world setting wherein each patient receives standard-of-care treatment selected by the treating physician. Outcomes include clinician- and patient-/family-reported outcomes, empowering both physician and patient decision making in new-onset systemic juvenile idiopathic arthritis.

  11. Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Markussen, Alice; Diness, Laura V

    2018-01-01

    , there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. METHODS: From November 2013 to January 2016, 50 patients with advanced...

  12. Impact on Medical Cost, Cumulative Survival, and Cost-Effectiveness of Adding Rituximab to First-Line Chemotherapy for Follicular Lymphoma in Elderly Patients: An Observational Cohort Study Based on SEER-Medicare

    Directory of Open Access Journals (Sweden)

    Robert I. Griffiths

    2012-01-01

    Full Text Available Rituximab improves survival in follicular lymphoma (FL, but is considerably more expensive than conventional chemotherapy. We estimated the total direct medical costs, cumulative survival, and cost-effectiveness of adding rituximab to first-line chemotherapy for FL, based on a single source of data representing routine practice in the elderly. Using surveillance, epidemiology, and end results (SEER registry data plus Medicare claims, we identified 1,117 FL patients who received first-line CHOP (cyclophosphamide (C, doxorubicin, vincristine (V, and prednisone (P or CVP +/− rituximab. Multivariate regression was used to estimate adjusted cumulative cost and survival differences between the two groups over four years after beginning treatment. The median age was 73 years (minimum 66 years, 56% had stage III-IV disease, and 67% received rituximab. Adding rituximab to first-line chemotherapy was associated with higher adjusted incremental total cost ($18,695; 95% Confidence Interval (CI $9,302–$28,643 and longer adjusted cumulative survival (0.18 years; 95% CI 0.10–0.27 over four years of followup. The expected cost-effectiveness was $102,142 (95% CI $34,531–296,337 per life-year gained. In routine clinical practice, adding rituximab to first-line chemotherapy for elderly patients with FL results in higher direct medical costs to Medicare and longer cumulative survival after four years.

  13. Learning Effective Treatment Pathways for Type-2 Diabetes from a clinical data warehouse.

    Science.gov (United States)

    Vashisht, Rohit; Jung, Ken; Shah, Nigam

    2016-01-01

    Treatment guidelines for management of type-2 diabetes mellitus (T2DM) are controversial because existing evidence from randomized clinical trials do not address many important clinical questions. Data from Electronic Medical Records (EMRs) has been used to profile first line therapy choices, but this work did not elucidate the factors underlying deviations from current treatment guidelines and the relative efficacy of different treatment options. We have used data from the Stanford Hospital to attempt to address these issues. Clinical features associated with the initial choice of treatment were effectively re-discovered using a machine learning approach. In addition, the efficacies of first and second line treatments were evaluated using Cox proportional hazard models for control of Hemoglobin A 1c . Factors such as acute kidney disorder and liver disorder were predictive of first line therapy choices. Sitagliptin was the most effective second-line therapy, and as effective as metformin as a first line therapy.

  14. Onyx embolization as a first line treatment for intracranial dural arteriovenous fistulas with cortical venous reflux

    International Nuclear Information System (INIS)

    Panagiotopoulos, V.; Forsting, M.; Wanke, I.; Moeller-Hartmann, W.; Asgari, S.; Sandalcioglu, I.E.

    2009-01-01

    Our purpose was to present our experience regarding embolization of intracranial dural arteriovenous fistulas (DAVFs) with cortical venous reflux using Onyx, a non-adhesive liquid embolic agent. From January 2006 to December 2007, 16 patients (12 men and 4 women) with a mean age of 61 years (range 42 - 78) with an intracranial DAVF with cortical venous reflux underwent at least one transarterial embolization using Onyx. According to the Cognard classification, 2 lesions were grade V, 5 were grade IV, 6 were grade III, 2 were grade IIa+b, and 1 was grade IIb. The clinical presentation included 5 hemorrhagic deficits, 10 non-hemorrhagic manifestations, and 1 patient was asymptomatic. Twenty-four embolization sessions were performed in 16 patients with an average of 3 arterial feeders (range 1 - 9) embolized per DAVF. Immediately after embolization, complete occlusion was achieved in 9 / 16 (56 %) patients after the first session. Further postembolization surgical treatment was performed in 3 patients. Partial reperfusion occurred in 1 patient at the time of mean follow-up of 3.7 months (range 0 - 12). Treatment has been completed for 11 / 16 patients with angiographic cure in 10 / 11 (91 %). An infratentorial bleeding complication related to embolization occurred in one patient with temporary worsening of the patient's gait disturbance. At the time of mean clinical follow-up of 4.5 months (range 0 - 12), no procedure-related permanent morbidity was added to our cohort. According to our experience, embolization of intracranial DAVFs with cortical venous drainage using Onyx is feasible with promising results, indicating stability at the time of mid-term follow-up. In very complex DAVFs additional embolization material might be necessary, and in some cases surgery is warranted. (orig.)

  15. Viable group A streptococci in macrophages during acute soft tissue infection.

    Directory of Open Access Journals (Sweden)

    Pontus Thulin

    2006-03-01

    Full Text Available Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections

  16. Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis

  17. Incidence and risk factors of major toxicity associated to first-line antituberculosis drugs for latent and active tuberculosis during a period of 10 years

    Directory of Open Access Journals (Sweden)

    Ana Tavares e Castro

    2015-05-01

    Full Text Available Introduction: Adverse drug reactions (ADR to first-line antituberculosis drugs are frequent and have important implications that may affect the effectiveness of treatment and course of tuberculosis (TB. Material and methods: Retrospective data analysis of clinical records and national registration forms from patients with ADR to first line antituberculosis that occurred between 2004 and 2013 at a Portuguese Pulmonology Diagnostic Centre, and from a case–control population matched by sex, age and year of initiation of treatment. Results: Of the 764 patients treated with antituberculosis drugs, 55 (52.7% male, 92.7% European, mean age 50.8 ± 19.5 years had at least one severe ADR and six had a second ADR, for a total of 61 events. The most frequent ADR were hepatotoxicity (86.9%, rash (8.2% and others, such as ocular toxicity, gastrointestinal intolerance and angioedema (4.9%. Isoniazid, alone or in combination, was the antituberculosis drug most associated to toxicity. Due to ADR, treatment time changed an average of 1.0 ± 2.6 months (range −3.4 to 10.6. There was no correlation between age or gender and the overall incidence of ADR although we found a significant association between younger age and an increased risk of hepatotoxicity (P = 0.035. There was also a statistically significant relationship between ADR and diabetes mellitus (P = 0.042 but not for other comorbidities or multi-resistant TB risk factors. Conclusions: This study found a high frequency of ADR with strong impact on subsequent therapeutic orientation. What seems to be of particular interest is the relationship between ADR and diabetes mellitus and the increased frequency of hepatotoxicity in younger patients. Keywords: Tuberculosis, Adverse reaction, Antituberculosis, Treatment

  18. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

    Directory of Open Access Journals (Sweden)

    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

  19. 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.

  20. Evaluation of artemisia mutant lines conducted from gamma irradiation treatment

    International Nuclear Information System (INIS)

    Ragapadmi Purnamaningsih; EG Lestari; M Syukur

    2010-01-01

    Cases of Malaria diseases attack in Indonesia has been increasing. Plasmodium falciparum the cause of malaria disease is now resistant to the usual medicine. One of malaria medicine which recommended by WHO is artemisinine compound extracted from Artemisia annua L plant. Low artemisinine content is one problem of Artemisia development in Indonesia. Increasing genetic variation using gamma irradiation is one alternative method to improve artemisinin content. In 2007, induce mutation had been done to artemisia seeds using gamma irradiation at dosage of 10-100 Gy. The good rooting planlet was regenerated and acclimatized in the green house, and then the seedling (M0 generation) was planted in the field at 1545 m asl. Plants derived from seeds without gamma irradiation treatment and cultured in vitro (in vitro control) were used as control. The result showed there were some morphological variations between the mutant lines (plant height, shape of the leaves and time of flowering). Ten mutant lines were selected based on biomass yield and analyzed for the artemisinine content.The result showed that artemisinine content of the mutant lines ranged from 0.44 - 1.41%, and it was significantly higher than that of in vitro control (0.43%). (author)

  1. High-Accuracy Quartic Force Field Calculations for the Spectroscopic Constants and Vibrational Frequencies of 1(exp 1)A' l-C3H(-): A Possible Link to Lines Observed in the Horsehead Nebula PDR

    Science.gov (United States)

    Fortenberry, Ryan C.; Huang, Xinchuan; Crawford, T. Daniel; Lee, Timothy J.

    2013-01-01

    It has been shown that rotational lines observed in the Horsehead nebula photon-dominated-region (PDR) are probably not caused by l-C3H+, as was originally suggested. In the search for viable alternative candidate carriers, quartic force fields are employed here to provide highly accurate rotational constants, as well as fundamental vibrational frequencies, for another candidate carrier: 1 (sup 1)A' C3H(-). The ab initio computed spectroscopic constants provided in this work are, compared to those necessary to define the observed lines, as accurate as the computed spectroscopic constants for many of the known interstellar anions. Additionally, the computed D-eff for C3H(-) is three times closer to the D deduced from the observed Horsehead nebula lines relative to l-C3H(+). As a result, 1 (sup 1)A' C3H(-). is a more viable candidate for these observed rotational transitions and would be the seventh confirmed interstellar anion detected within the past decade and the first C(sub n)H(-) molecular anion with an odd n.

  2. Production of viable male unreduced gametes in Brassica interspecific hybrids is genotype specific and stimulated by cold temperatures

    Directory of Open Access Journals (Sweden)

    Cowling Wallace A

    2011-06-01

    Full Text Available Abstract Background Unreduced gametes (gametes with the somatic chromosome number may provide a pathway for evolutionary speciation via allopolyploid formation. We evaluated the effect of genotype and temperature on male unreduced gamete formation in Brassica allotetraploids and their interspecific hybrids. The frequency of unreduced gametes post-meiosis was estimated in sporads from the frequency of dyads or giant tetrads, and in pollen from the frequency of viable giant pollen compared with viable normal pollen. Giant tetrads were twice the volume of normal tetrads, and presumably resulted from pre-meiotic doubling of chromosome number. Giant pollen was defined as pollen with more than 1.5 × normal diameter, under the assumption that the doubling of DNA content in unreduced gametes would approximately double the pollen cell volume. The effect of genotype was assessed in five B. napus, two B. carinata and one B. juncea parents and in 13 interspecific hybrid combinations. The effect of temperature was assessed in a subset of genotypes in hot (day/night 30°C/20°C, warm (25°C/15°C, cool (18°C/13°C and cold (10°C/5°C treatments. Results Based on estimates at the sporad stage, some interspecific hybrid genotypes produced unreduced gametes (range 0.06 to 3.29% at more than an order of magnitude higher frequency than in the parents (range 0.00% to 0.11%. In nine hybrids that produced viable mature pollen, the frequency of viable giant pollen (range 0.2% to 33.5% was much greater than in the parents (range 0.0% to 0.4%. Giant pollen, most likely formed from unreduced gametes, was more viable than normal pollen in hybrids. Two B. napus × B. carinata hybrids produced 9% and 23% unreduced gametes based on post-meiotic sporad observations in the cold temperature treatment, which was more than two orders of magnitude higher than in the parents. Conclusions These results demonstrate that sources of unreduced gametes, required for the triploid

  3. Strengthening Agricultural Research Capacity for Viable Extension ...

    African Journals Online (AJOL)

    Strengthening Agricultural Research Capacity for Viable Extension Policies in Nigeria: An Exploration of Ricoeur's Hermeneutic Theory for Analysing Extension Research. ... Progressively more, researchers use hermeneutic philosophy to inform the conduct of interpretive research. Analogy between the philosophical ...

  4. First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

  5. A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

    Science.gov (United States)

    Watt, Maureen; McCrea, Charles; Johal, Sukhvinder; Posnett, John; Nazir, Jameel

    2016-10-01

    Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients. In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.

  6. First treatment contact for ADHD: predictors of and gender differences in treatment seeking.

    Science.gov (United States)

    Dakwar, Elias; Levin, Frances R; Olfson, Mark; Wang, Shuai; Kerridge, Bradley; Blanco, Carlos

    2014-12-01

    For attention-deficit hyperactivity disorder (ADHD), treatment seeking is a critical first step in treatment initiation and remains insufficiently understood. The aims of this study were to estimate ADHD treatment-seeking probabilities over the lifetime and to identify predictors of treatment seeking for ADHD separately for males and females. Data were drawn from 2001 to 2005 as part of the National Epidemiologic Survey on Alcohol and Related Conditions, a two-wave face-to-face survey conducted by the National Institute on Alcohol Abuse and Alcoholism (N=34,653). The lifetime cumulative probability of ADHD treatment seeking was estimated at 55%. Males identifying as African American, with less than 12 years of education, or paranoid personality disorder or in an older cohort (>30 years old) at the time of interview were more likely to experience delays, whereas males with comorbid alcohol dependence, dysthymic disorder, borderline personality disorder, or histrionic personality disorder were less likely. Among females, older age (>44 years) was the only predictor of a delay to first treatment seeking, whereas bipolar disorder was associated with more rapid treatment seeking. Age of onset had opposite effects on treatment-seeking delays by gender; males but not females with early-onset ADHD were more likely to experience treatment-seeking delays. A large proportion of persons with ADHD do not seek treatment. Furthermore, treatment seeking by males was affected by a greater number of identifiable characteristics, suggesting that males might be more responsive to efforts directed toward expediting treatment entry. Future research should explore how to facilitate early access to treatment for individuals with ADHD.

  7. The Role of Hysteroscopy in the Diagnosis and Treatment of Adenomyosis

    Directory of Open Access Journals (Sweden)

    Attilio Di Spiezio Sardo

    2017-01-01

    Full Text Available Uterine adenomyosis is a common gynecologic disorder in women of reproductive age, characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Dysmenorrhea, abnormal uterine bleeding, chronic pelvic pain, and deep dyspareunia are common symptoms of this pathological condition. However, adenomyosis is often an incidental finding in specimens obtained from hysterectomy or uterine biopsies. The recent evolution of diagnostic imaging techniques, such as transvaginal sonography, hysterosalpingography, and magnetic resonance imaging, has contributed to improving accuracy in the identification of this pathology. Hysteroscopy offers the advantage of direct visualization of the uterine cavity while giving the option of collecting histological biopsy samples under visual control. Hysteroscopy is not a first-line treatment approach for adenomyosis and it represents a viable option only in selected cases of focal or diffuse “superficial” forms. During office hysteroscopy, it is possible to enucleate superficial focal adenomyomas or to evacuate cystic haemorrhagic lesions of less than 1.5 cm in diameter. Instead, resectoscopic treatment is indicated in cases of superficial adenomyotic nodules > 1.5 cm in size and for diffuse superficial adenomyosis. Finally, endometrial ablation may be performed with the additional removal of the underlying myometrium.

  8. First Detections of the [N II] 122 micron Line at High Redshift: Demonstrating the Utility of the Line for Studying Galaxies in the Early Universe

    Science.gov (United States)

    Ferkinhoff, Carl; Brisbin, Drew; Nikola, Thomas; Parshley, Stephen C.; Stacey, Gordon J.; Phillips, Thomas G.; Falgarone, Edith; Benford, Dominic J.; Staguhn, Johannes G.; Tucker, Carol E.

    2011-01-01

    We report the first detections of the [N II] 122 micron line from a high-redshift galaxy. The line was strongly (>6(sigma)) detected from SMMJ02399-0136, and H1413 + 117 (the Cloverleaf QSO) using the Redshift (zeta) and Early Universe Spectrometer on the Caltech Submillimeter Observatory. The lines from both sources are quite bright with line to far-infrared (FIR) continuum luminosity ratios that are approx.7.0 x 10(exp -4) (Cloverleaf) and 2.1 x 10(exo -3) (SMMJ02399). With ratios 2-10 times larger than the average value for nearby galaxies, neither source exhibits the line to continuum deficits seen in nearby sources. The line strengths also indicate large ionized gas fractions, approx.8%-17% of the molecUlar gas mass. The [O III]/[N II] line ratio is very sensitive to the effective temperature of ionizing stars and the ionization parameter for emission arising in the narrow-line region (NLR) of an active galactic nucleus (AGN). Using Our previous detection of the [O III] 88 micron line, the [O III]/[N II]line ratio for SMMJ02399-0136 indicates that the dominant source of the line emission is either stellar H II regions ionized by O9.5 stars, or the NLR of the AGN with ionization parameter log(U) = -3.3 to -4.0. A composite system, where 30%-50% of the FIR lines arise in the NLR also matches the data. The Cloverleaf is best modeled by a superposition of approx.200 M82-like starbursts accounting for all of the FIR emission and 43% of the [N II]line. The remainder may come from the NLR. This war!< demonstrates the utility of the [N II] and [O III] lines in constraining properties of the ionized medium.

  9. Treatment strategies for the infertile polycystic ovary syndrome patient.

    Science.gov (United States)

    Tannus, Samer; Burke, Yechiel Z; Kol, Shahar

    2015-11-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Infertility is a prevalent presenting feature of PCOS, and approximately 75% of these women suffer infertility due to anovulation. Lifestyle modification is considered the first-line treatment and is associated with improved endocrine profile. Clomiphene citrate (CC) should be considered as the first line pharmacologic therapy for ovulation induction. In women who are CC resistant, second-line treatment should be considered, as adding metformin, laparoscopic ovarian drilling or treatment with gonadotropins. In CC treatment failure, Letrozole could be an alternative or treatment with gonadotropins. IVF is considered the third-line treatment; the 'short', antagonist-based protocol is the preferred option for PCOS patients, as it is associated with lower risk of developing ovarian hyperstimulation syndrome (specifically by using a gonadotropin--releasing hormone agonist as ovulation trigger), but with comparable outcomes as the long protocol.

  10. Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines

    Science.gov (United States)

    2014-01-01

    Background Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. Results We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. Conclusions KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma. PMID:25022346

  11. Cellular response to 5-fluorouracil (5-FU in 5-FU-resistant colon cancer cell lines during treatment and recovery

    Directory of Open Access Journals (Sweden)

    Kravik Katherine L

    2006-05-01

    Full Text Available Abstract Background Treatment of cells with the anti-cancer drug 5-fluorouracil (5-FU causes DNA damage, which in turn affects cell proliferation and survival. Two stable wild-type TP53 5-FU-resistant cell lines, ContinB and ContinD, generated from the HCT116 colon cancer cell line, demonstrate moderate and strong resistance to 5-FU, respectively, markedly-reduced levels of 5-FU-induced apoptosis, and alterations in expression levels of a number of key cell cycle- and apoptosis-regulatory genes as a result of resistance development. The aim of the present study was to determine potential differential responses to 8 and 24-hour 5-FU treatment in these resistant cell lines. We assessed levels of 5-FU uptake into DNA, cell cycle effects and apoptosis induction throughout treatment and recovery periods for each cell line, and alterations in expression levels of DNA damage response-, cell cycle- and apoptosis-regulatory genes in response to short-term drug exposure. Results 5-FU treatment for 24 hours resulted in S phase arrests, p53 accumulation, up-regulation of p53-target genes on DNA damage response (ATF3, GADD34, GADD45A, PCNA, cell cycle-regulatory (CDKN1A, and apoptosis-regulatory pathways (FAS, and apoptosis induction in the parental and resistant cell lines. Levels of 5-FU incorporation into DNA were similar for the cell lines. The pattern of cell cycle progression during recovery demonstrated consistently that the 5-FU-resistant cell lines had the smallest S phase fractions and the largest G2(/M fractions. The strongly 5-FU-resistant ContinD cell line had the smallest S phase arrests, the lowest CDKN1A levels, and the lowest levels of 5-FU-induced apoptosis throughout the treatment and recovery periods, and the fastest recovery of exponential growth (10 days compared to the other two cell lines. The moderately 5-FU-resistant ContinB cell line had comparatively lower apoptotic levels than the parental cells during treatment and recovery

  12. Investigation of Removal Capacities of Biofilters for Airborne Viable Micro-Organisms

    Science.gov (United States)

    Soret, Rémi; Fanlo, Jean-Louis; Malhautier, Luc; Geiger, Philippe; Bayle, Sandrine

    2018-01-01

    New emerging issues appears regarding the possible aerosolization of micro-organisms from biofilters to the ambient air. Traditional bioaerosol sampling and cultural methods used in literature offer relative efficiencies. In this study, a new method revolving around a particle counter capable of detecting total and viable particles in real time was used. This counter (BioTrak 9510-BD) uses laser-induced fluorescence (LIF) technology to determine the biological nature of the particle. The concentration of viable particles was measured on two semi-industrial pilot scale biofilters in order to estimate the Removal Efficiency in viable particles (REvp) in stable conditions and to examine the influence of pollutant feeding and relative humidification of the gaseous effluent on the REvp. The REvp of biofilters reached near 80% and highlighted both the stability of that removal and the statistical equivalence between two identical biofilters. Pollutant deprivation periods of 12 h, 48 h and 30 days were shown to have no influence on the biofilters’ removal capacity, demonstrating the robustness and adaptation capacities of the flora. In contrast, a 90-day famine period turned the biofilters into emitters of viable particles. Finally, the humidification of the effluent was shown to negatively influence the removal capacity for viable particles, as drying off the air was shown to increase the REvp from 60 to 85%. PMID:29562709

  13. Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

    International Nuclear Information System (INIS)

    Wu, Jianqiu; Song, Yongping; Su, Liping; Xu, Li; Chen, Tingchao

    2016-01-01

    The efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL. Treatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120 days after the last R-chemo administration. Overall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2 % (complete response [CR], 55.0 %; CR unconfirmed [CRu] 18.2 %; and partial response [PR], 20.9 %). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5 cm negatively correlated with CR + CRu, whereas age and HBsAg positivity negatively correlated with CR. This study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures

  14. Cobalt Chloride Treatment Used to Ablate the Lateral Line System Also Impairs the Olfactory System in Three Freshwater Fishes.

    Directory of Open Access Journals (Sweden)

    Julie M Butler

    Full Text Available Fishes use multimodal signals during both inter- and intra-sexual displays to convey information about their sex, reproductive state, and social status. These complex behavioral displays can include visual, auditory, olfactory, tactile, and hydrodynamic signals, and the relative role of each sensory channel in these complex multi-sensory interactions is a common focus of neuroethology. The mechanosensory lateral line system of fishes detects near-body water movements and is implicated in a variety of behaviors including schooling, rheotaxis, social communication, and prey detection. Cobalt chloride is commonly used to chemically ablate lateral line neuromasts, thereby eliminating water-movement cues to test for mechanosensory-mediated behavioral functions. However, cobalt acts as a nonspecific calcium channel antagonist and could potentially disrupt function of all superficially located sensory receptor cells, including those for chemosensing. Here, we examined whether CoCl2 treatment used to ablate the lateral line system also impairs olfaction in three freshwater fishes, the African cichlid fish Astatotilapia burtoni, goldfish Carassius auratus, and the Mexican blind cavefish Astyanax mexicanus. To examine the impact of CoCl2 on the activity of peripheral receptors, we quantified DASPEI fluorescence intensity of the olfactory epithelium from fish exposed to control and CoCl2 solutions. In addition, we examined brain activation in olfactory processing regions of A. burtoni immersed in either control or cobalt solutions. All three species exposed to CoCl2 had decreased DASPEI staining of the olfactory epithelium, and in A. burtoni, cobalt treatment caused reduced neural activation in olfactory processing regions of the brain. To our knowledge this is the first empirical evidence demonstrating that the same CoCl2 treatment used to ablate the lateral line system also impairs olfactory function. These data have important implications for the use of

  15. New developments in cognitive behavioral therapy as the first-line treatment of insomnia

    OpenAIRE

    Siebern, Allison T; Manber, Rachel

    2011-01-01

    Allison T Siebern, Rachel ManberSleep Medicine Center, Stanford University School of Medicine, Redwood City, California, USAAbstract: Insomnia is the most common sleep disorder. Psychological, behavioral, and biological factors are implicated in the development and maintenance of insomnia as a disorder, although the etiology of insomnia remains under investigation, as it is still not fully understood. Cognitive behavioral therapy for insomnia (CBTI) is a treatment for insomnia that is grounde...

  16. Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: a pilot study of 36 patients.

    Science.gov (United States)

    Haioun, C; Mounier, N; Quesnel, B; Morel, P; Rieux, C; Beaujean, F; Marolleau, J P; Belhadj, K; Simon, D; Gaulard, P H; Lepage, E; Gisselbrecht, C H; Reyes, F

    2001-12-01

    In the previous LNH87-2 study, consolidative high-dose therapy followed by stem cell transplantation (HDT) improved disease-free survival, as well as survival for patients (pts) presenting with two or three factors of the age-adjusted international prognostic index (Aa-IPI) in first complete remission (CR). In order to improve further the outcome of such patients, we conducted a pilot study of consolidative tandem autotranplant. Thirty-six patients (pts) under 60 years of age with two or three factors of the Aa-IPI were enrolled. Their main characteristics were: diffuse large B-cell lymphoma (83%), Aa-IPI three factors (50%), and marrow involved (36)%. The procedure consisted of 1) induction with four cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) 2) in responding pts, peripheral blood stem cell (PBSC) collection after the fourth cycle of ACVBP (11 pts) or after an additional mobilization regimen (Cyclophosphamide-VP16) (17 pts) 3) a first HDT (mitoxantrone, cyclophosphamide, VP16 and carmustine) followed by PBSC infusion 4) a second HDT (busulfan, carboplatin and melphalan) followed by PBSC infusion. Among the 29 patients responding to induction, 28 received the first HDTand 24 the second. The rates of three-year-event free survival and survival are 47% (95% confidence interval (95% CI: 31%-63%) and 50% (95% CI: 37%-69%), respectively. Eighteen patients remained free of evolutive disease and 18 patients have died, 15 from disease progression and three from treatment-related toxicity after tandem transplant (two veno-occlusive disease and one cerebral toxoplasmosis). We conclude that tandem transplant did not improve the results of the LNH87-2 study in which patients received a single consolidative HDT.

  17. Patterns of pharmacologic treatment in US patients with acromegaly.

    Science.gov (United States)

    Broder, Michael S; Chang, Eunice; Ludlam, William H; Neary, Maureen P; Carmichael, John D

    2016-05-01

    To establish a baseline pattern of care across academic and community settings, it is important to examine the contemporary treatment of acromegaly. We characterized medical treatment patterns for acromegaly in the US to develop a basis for tracking concordance with guidelines. Acromegaly patients were identified in two commercial claims databases for this retrospective analysis. Study subjects had ≥2 medical claims with acromegaly (ICD-9-CM code 253.0) and ≥1 claim for pharmacotherapy (bromocriptine, cabergoline, octreotide SA, octreotide LAR, lanreotide, or pegvisomant) in the study timeframe (1 January 2002-31 December 2013). Patients were considered newly treated if they were continuously enrolled for ≥6 months before first observed treatment and had no claim for pharmacologic treatment during that time. Outcomes included various pharmacotherapies, including combination treatments, and differences between lines of therapy. A total of 3150 patients had ≥1 pharmacotherapy (mean age: 46.5 years; 50.1% were female); 1471 were newly treated. Somatostatin receptor ligands (SRLs) were the most common drug class used first line (57.2%); cabergoline (27.8%) was the most common treatment, followed by octreotide LAR (22.3%) and lanreotide (19.7%). SRLs were also the most commonly used second-line (42.8%) and third-line pharmacotherapies (43.9%), with combination therapy (23.2%) and octreotide LAR (19.8%) as the most commonly used treatments, respectively. This study, representing the largest claims-based analysis of acromegaly to date, used two databases across a 12 year period to examine complex treatment patterns in a difficult-to-study disease. Although wide variation in acromegaly treatment patterns exists in US clinical practice, in first-line, second-line, and third-line therapy, SRL was the most commonly used drug class. Drug combinations also varied considerably across lines of therapy. The switching between different monotherapies and varied use of drugs

  18. First-line managers' descriptions and reflections regarding their staff's access to empowering structures.

    Science.gov (United States)

    Skytt, Bernice; Hagerman, Heidi; Strömberg, Annika; Engström, Maria

    2015-11-01

    To elucidate first-line managers' descriptions and reflections regarding their staff's access to empowering structures using Kanter's theory of structural empowerment. Good structural conditions within workplaces are essential to employees' wellbeing, and their ability to access empowerment structures is largely dependent on the management. Twenty-eight first-line managers in elderly care were interviewed. Deductive qualitative content analysis was used to analyse data. Managers perceived that staff had varying degrees of access to the empowering structures described in Kanter's theory - and that they possessed formal power in their roles as contact persons and representatives. The descriptions mostly started from the managers' own actions, although some started from the needs of staff members. All managers described their staff's access to the empowering structures in Kanter's theory as important, yet it seemed as though this was not always reflected on and discussed as a strategic issue. Managers could make use of performance and appraisal dialogues to keep up to date on staff's access to empowering structures. Recurrent discussions in the management group based on such current information could promote staff's access to power through empowering structures and make job definitions a strategic issue in the organisation. © 2014 John Wiley & Sons Ltd.

  19. Nanostructured nickel (II) phthalocyanine-MWCNTs as viable nanocomposite platform for electrocatalytic detection of asulam pesticide at neutral pH conditions

    CSIR Research Space (South Africa)

    Siswana, MP

    2010-08-01

    Full Text Available This work reports for the first time that nanostructured nickel (II) phthalocyanine/multiwalled carbon nanotubes composite supported on a basal plane pyrolytic electrode (NiPcNP/MWCNT-BPPGE) could potentially serve as a viable platform...

  20. Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

    Science.gov (United States)

    Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

    2014-05-01

    Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (SAiL study. No new safety signals were reported.

  1. Spatiotemporal Dynamics of Total Viable Vibrio spp. in a NW Mediterranean Coastal Area.

    Science.gov (United States)

    Girard, Léa; Peuchet, Sébastien; Servais, Pierre; Henry, Annabelle; Charni-Ben-Tabassi, Nadine; Baudart, Julia

    2017-09-27

    A cellular approach combining Direct Viable Counting and Fluorescent In Situ Hybridization using a one-step multiple-probe technique and Solid Phase Cytometry (DVC-FISH-SPC) was developed to monitor total viable vibrios and cover the detection of a large diversity of vibrios. FISH combined three probes in the same assay and targeted sequences located at different positions on the 16S rRNA of Vibrio and Aliivibrio members. We performed a 10-month in situ study to investigate the weekly dynamics of viable vibrios relative to culturable counts at two northwestern Mediterranean coastal sites, and identified the key physicochemical factors for their occurrence in water using a multivariate analysis. Total viable and culturable cell counts showed the same temporal pattern during the warmer season, whereas the ratios between both methods were inverted during the colder seasons (<15°C), indicating that some of the vibrio community had entered into a viable but non-culturable (VBNC) state. We confirmed that Seawater Surface Temperature explained 51-62% of the total variance in culturable counts, and also showed that the occurrence of viable vibrios is controlled by two variables, pheopigment (15%) and phosphate (12%) concentrations, suggesting that other unidentified factors play a role in maintaining viability.

  2. 9 CFR 113.26 - Detection of viable bacteria and fungi except in live vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Detection of viable bacteria and fungi... VECTORS STANDARD REQUIREMENTS Standard Procedures § 113.26 Detection of viable bacteria and fungi except... required to be free of viable bacteria and fungi, they shall also be tested as prescribed in this section...

  3. Changes in mutational status during third-line treatment for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Pallisgaard, Niels; Andersen, Rikke Fredslund

    2014-01-01

    and BRAF in plasma and report the changes during third line treatment with cetuximab and irinotecan. One-hundred-and-eight patients received irinotecan 350 mg/m2 q3w and weekly cetuximab (250 mg/m2) until progression (RECIST) or unacceptable toxicity. cfDNA and number of mutated KRAS/BRAF alleles in plasma...

  4. Can Malin's gravitational-field equations be modified to obtain a viable theory of gravity to obtain a viable theory of gravity to obtain a viable theory of gravity

    International Nuclear Information System (INIS)

    Smalley, L.L.; Prestage, J.

    1976-01-01

    Malin's gravitational theory, which was recently shown by Lindblom and Nester to be incorrect, is modified by means of a recently proposed method for obtaining viable gravitational theories. The resulting self-consistent theory, which is in effect a Rastall-type modification of the Einstein theory, exhibits nonconservation of momentum, yet agrees with all experimental limits known to date within the PPN framework

  5. Combination treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Holbech, Jakob Vormstrup; Jung, Anne; Jonsson, Torsten

    2017-01-01

    BACKGROUND: Current Danish treatment algorithms for pharmacological treatment of neuropathic pain (NeP) are tricyclic antidepressants (TCA), gabapentin and pregabalin as first-line treatment for the most common NeP conditions. Many patients have insufficient pain relief on monotherapy, but combin...

  6. 46 CFR 197.314 - First aid and treatment equipment.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false First aid and treatment equipment. 197.314 Section 197... HEALTH STANDARDS GENERAL PROVISIONS Commercial Diving Operations Equipment § 197.314 First aid and... consists of— (i) Basic first aid supplies; and (ii) Any additional supplies necessary to treat minor trauma...

  7. Monotone viable trajectories for functional differential inclusions

    Science.gov (United States)

    Haddad, Georges

    This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

  8. Viable acrosome-intact human spermatozoa in the ejaculate as a marker of semen quality and fertility status

    DEFF Research Database (Denmark)

    Egeberg Palme, Dorte Louise; Rehfeld, Anders; Bang, Anne Kirstine

    2018-01-01

    STUDY QUESTION: Is it possible, in an unbiased and clinical relevant way, to determine the number of viable acrosome-intact human spermatozoa in ejaculates and to use this as a measure of fertility chances? SUMMARY ANSWER: Image cytometry enables easy and unbiased quantification of viable acrosome......-intact spermatozoa and it correlates with semen quality and fertility status. WHAT IS KNOWN ALREADY: The presence of the acrosome and its ability to respond to physiological inducers (e.g. progesterone) in the female reproductive tract at the appropriate time and place is required for fertilization. However......, the available assays are labor intensive and therefore not used clinically. STUDY DESIGN, SIZE, DURATION: Washed semen samples and capacitated swim-up fractions from volunteers were used to develop the assay. Subsequently washed ejaculates from patients in fertility treatment (n = 156), proven fertile men (n...

  9. Advanced colorectal cancer, refractory to infusional fluorouracil treatment: efficacy of second line fluorouracil in combination with a different biochemical modulation

    NARCIS (Netherlands)

    van Halteren, H. K.; Wagener, D. J.; Vreugdenhil, G.; Punt, C. J.

    1997-01-01

    Currently there is no standard second line treatment for patients with advanced colorectal cancer (ACC). Previous reports have demonstrated that some patients may benefit from second line infusional 5-fluorouracil (5-FU) after failing 5-FU bolus treatment. We retrospectively studied the efficacy and

  10. Treatment initiatives after radiological accidents: TIARA first step

    International Nuclear Information System (INIS)

    Menetrier, F.; Berard, P.; Joussineau, S.; Stradling, N.; Hodgson, V.; List, MA.; Morcillo, W.; Paile, D.; Holt, T.; Eriksson

    2006-01-01

    Full text of publication follows: T.I.A.R.A. [Treatment Initiatives After Radiological Accidents] project is a consortium of 8 European partners. This project is part of the Preparatory Action on Security Research recently launched by the European Commission. The Preparatory Action is intended to reach preliminary conclusions on the needs for the security of European Union citizens before the launch of the Security Research Programme in 2007. The principal purpose of T.I.A.R.A. is to constitute a European network which will participate in enhancing the management of a crisis in the hypothesis of a malevolent dispersal of radionuclides in a public place. The main concern is to identify and define effective medical treatments for internal radioactive contamination. A preview of the state of treatment of contamination by radionuclides (especially actinides) in Europe highlights the following points: a decrease in the number of physicians with experience of treatment, a need for generalised agreement on treatment decisions and protocols, unanticipated operational issues and research into new treatments. If treatment is to be effective then several factors must be addressed and these include: firstly, the availability of effective specific treatment for the radionuclides involved, their rapid transport to and distribution of the drugs at the place of the malevolent dispersal and the easy administration of the drug even if numerous people are contaminated. The objectives of T.I.A.R.A. are threefold. First to provide straightforward guidance on dose assessment and efficacy of treatment which is readily understood by health physicists and physicians who do not have detailed knowledge and experience in radiological protection matters. Second, to foresee the operational needs for treating persons when there are mass casualties. Third, to monitor scientific and technological development on research into new treatments. Progress in all these aspects of the project will be

  11. Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, L H; Sindrup, S H; Christiansen, I

    2017-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment...... treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function...... tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG...

  12. Tomography high Resolution CT findings of nontuberculous mycobacterial pulmonary disease: Comparison between the first treatment and the re treatment group

    Energy Technology Data Exchange (ETDEWEB)

    Gwak, Soon Hyuk; Cho, Bum Sang; Jeon, Min Hee; Kim, Eun Young; Kang, Min Ho; Yi, Kyung Sik; Lee, Seung Young; Kim, Sung Jin; Lee, Ki Man [Chungbuk National Univ., Cheongju, (Korea, Republic of)

    2012-06-15

    To analyze and compare the thin section CT findings of first and re treatment nontuberculous mycobacterial (NTM) pulmonary disease. Between January 2005 and April 2010, 121 patients with positive sputum culture for NTM were recruited. We included only 32 patients underwent high resolution chest CT and were confirmed by American Thoracic Society criteria NTM pulmonary infection (first treatment 15, re treatment 17 patients). CT images of 32 patients were reviewed retrospectively. We evaluated the frequency and laterality of the followings; nodule, increased density, bronchial change, parenchymal change. The significantly frequent CT findings of the re treatment NTM group were well defined nodules (retreatment 82.4%, first treatment 33.3%, p = 0.00), consolidations (retreatment 88.2%, first treatment 53.3%, p = 0.03), bronchial changes (bronchiectasis; retreatment 100%, first treatment 66.6%, p = 0.01, bronchial narrowing; retreatment 23.5%, first treatment 0%, p = 0.04 and mucoid impaction; retreatment-58.8%, first treatment-20.0%, p = 0.03) and atelectasis with bronchiectasis (retreatment-88.2%, first treatment 26.7%, p = 0.00). However, most of the evaluated thin section CT findings, such as centrilobular and ill defined nodules, lobular, segmental and subpleural consolidations, ground glass attenuation, bronchial wall thickening, cavities, pleural lesions, fibrotic band, emphysema and laterality of lesions, have not shown significant differences between first treatment and the re treatment group. Thin section CT findings of well defined nodules, consolidations, bronchial changes (bronchiectasis, bronchial narrowing and mucoid impaction) and atelectasis with bronchiectasis are highly suggestive of re treatment NTM pulmonary disease.

  13. AEC sets basic policy line on treatment and disposal of radioactive waste

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    The AEC's new policy line for the treatment and disposal of radioactive wastes is explained with three tables added. The first table was prepared by MITI's Nuclear Fuel Advisory Committee regarding the projections on the amounts of radioactive wastes to be discharged from nuclear power plants, fuel fabrication plants and reprocessing plants, and the other two tables were made by the AEC committee on technical development of radioactive waste management, the one proposed the developmental steps necessary for establishing waste management technologies, and the other showed the related research and development items with target time schedule. The proper treatment and disposal of radioactive waste S are the problems that have to be resolved prior to the full development and utilization of nuclear energy. The Atomic Energy Commission set up a committee on July 29, 1975, to discuss the technologies on the management of radioactive wastes. The principle essential to the radioactive waste management was set, and it is desirable that this principle is put into practice with the cooperation and understanding of the people and all parties concerned. The countermeasures proposed will be subject to review yet as the technology makes further progress and they are as follows: on the high level radioactive waste management and the low-and intermediate-level radioactive waste management, the basic idea, targets and measures are given, and the methods for promoting experimental ocean dumping of low level radioactive wastes are proposed. (Iwakiri, K.)

  14. Course and predictors of suicidality over the first two years of treatment in first-episode schizophrenia spectrum psychosis

    DEFF Research Database (Denmark)

    Melle, Ingrid; Johannessen, Jan Olav; Friis, Svein

    2010-01-01

    the objective of this study was to investigate the course of suicidal behavior over the first 2 years of comprehensive, integrated treatment in two groups of patients with DSM-IV first episode schizophrenia spectrum psychosis, where one group was recruited through an early detection program. We h......, with no between-groups differences. Severe suicidality (plans and attempts) was predicted by drug abuse, dissatisfaction with life and severe suicidality at start of treatment.......the objective of this study was to investigate the course of suicidal behavior over the first 2 years of comprehensive, integrated treatment in two groups of patients with DSM-IV first episode schizophrenia spectrum psychosis, where one group was recruited through an early detection program. We...... have previously shown that the rate of severe suicidal behavior was lower in the earlier detected group than in the other. First episode schizophrenia is a high risk period for suicidality, but we found low rates of completed suicides and suicide attempts in both groups after 2 years in treatment...

  15. Commissioning and first clinical application of mARC treatment

    International Nuclear Information System (INIS)

    Dzierma, Yvonne; Nuesken, Frank G.; Kremp, Stephanie; Palm, Jan; Licht, Norbert P.; Ruebe, Christian

    2014-01-01

    The modulated arc (mARC) technique has recently been introduced for Siemens ARTISTE linear accelerators. We present the first experiences with the commissioning of the system and first patient treatments. Treatment planning and delivery are presented for the Prowess Panther treatment planning system or, alternatively, an in-house code. Dosimetric verification is performed both by point dose measurements and in 3D dose distribution. Depending on the target volume, one or two arcs can be used to create highly conformal plans. Dosimetric verification of the converted mARC plans with step-and-shoot plans shows deviations below 1 % in absolute point dose; in the 3D dose distribution, over 95 % of the points pass the 3D gamma criteria (3 % deviation in local dose and 3 mm distance to agreement for doses > 20 % of the maximum). Patient specific verification of the mARC dose distribution with the calculations has a similar pass rate. Treatment times range between 2 and 5 min for a single arc. To our knowledge, this is the first report of clinical application of the mARC technique. The mARC offers the possibility to save significant amounts of time, with single-arc treatments of only a few minutes achieving comparable dose distribution to IMRT plans taking up to twice as long. (orig.) [de

  16. Introduction of dermatome shaving as first line treatment of chronic tattoo reactions

    DEFF Research Database (Denmark)

    Sepehri, Mitra; Jørgensen, Bo; Serup, Jørgen

    2015-01-01

    BACKGROUND/AIMS: Chronic tattoo reactions requiring treatment have increased. Laser removal is not ideal for removal of allergic reactions. Surgical removal of culprit pigment situated in the outer dermis by dermatome shaving is rational and need to be revisited. MATERIALS/METHODS: Fifty four...... tattoos with chronic reactions in 50 patients were treated with dermatome shaving. Tattoos with red/red nuances dominated the material. In total, 52 operations were performed in infiltration and 2 in general anaesthesia. Shaving was performed to the level in the dermis free of tattoo pigment as assessed...... visually by the surgeon. RESULTS: Operative complications were few. Healing occurred over weeks as normal for this procedure. On a rating scale from 0 to 4, 4 as most severe, the patient's severity rating of symptoms in their tattoo declined from 3.2 pre-operatively to 1.0, 0.8 and 0.7 after 3, 6 and 12...

  17. Treatment Algorithms in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Muangchan, Chayawee; van Vollenhoven, Ronald F; Bernatsky, Sasha R; Smith, C Douglas; Hudson, Marie; Inanç, Murat; Rothfield, Naomi F; Nash, Peter T; Furie, Richard A; Senécal, Jean-Luc; Chandran, Vinod; Burgos-Vargas, Ruben; Ramsey-Goldman, Rosalind; Pope, Janet E

    2015-09-01

    To establish agreement on systemic lupus erythematosus (SLE) treatment. SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement). Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and

  18. Viable-but-Nonculturable Listeria monocytogenes and Salmonella enterica Serovar Thompson Induced by Chlorine Stress Remain Infectious

    Directory of Open Access Journals (Sweden)

    Callum J. Highmore

    2018-04-01

    Full Text Available The microbiological safety of fresh produce is monitored almost exclusively by culture-based detection methods. However, bacterial food-borne pathogens are known to enter a viable-but-nonculturable (VBNC state in response to environmental stresses such as chlorine, which is commonly used for fresh produce decontamination. Here, complete VBNC induction of green fluorescent protein-tagged Listeria monocytogenes and Salmonella enterica serovar Thompson was achieved by exposure to 12 and 3 ppm chlorine, respectively. The pathogens were subjected to chlorine washing following incubation on spinach leaves. Culture data revealed that total viable L. monocytogenes and Salmonella Thompson populations became VBNC by 50 and 100 ppm chlorine, respectively, while enumeration by direct viable counting found that chlorine caused a <1-log reduction in viability. The pathogenicity of chlorine-induced VBNC L. monocytogenes and Salmonella Thompson was assessed by using Caenorhabditis elegans. Ingestion of VBNC pathogens by C. elegans resulted in a significant life span reduction (P = 0.0064 and P < 0.0001, and no significant difference between the life span reductions caused by the VBNC and culturable L. monocytogenes treatments was observed. L. monocytogenes was visualized beyond the nematode intestinal lumen, indicating resuscitation and cell invasion. These data emphasize the risk that VBNC food-borne pathogens could pose to public health should they continue to go undetected.

  19. Mutagenic effects of gamma rays on the frequency and spectrum of chlorophyll and viable macro mutations in chilli (Capsicum annuum L.)

    International Nuclear Information System (INIS)

    Rangaiah, S.; Manjunath, A.; Puttaramanaik

    2004-01-01

    In the present study, uniform dry and healthy seeds of two cultivars of chilli namely Ceylon and Byadagi were exposed to 60 Co gamma rays at 5, 10, 15, 20, 25, 30, 35 and 40 krad doses at BARC, Mumbai. Thus there were total 18 treatments, eight different doses of gamma rays and one control in each cultivar. The M2 populations were compared with the respective control populations for chlorophyll and viable mutations. The treated populations were compared with the respective control populations for chlorophyll mutations (M2 and M3) and viable mutations (M2)' The results of the study are presented

  20. Factors associated with recent unsuppressed viral load in HIV-1-infected patients in care on first-line antiretroviral therapy in South Africa.

    Science.gov (United States)

    Joseph Davey, D; Abrahams, Z; Feinberg, M; Prins, M; Serrao, C; Medeossi, B; Darkoh, E

    2018-05-01

    Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs when treatment fails to suppress a person's VL and is associated with decreased survival and increased HIV transmission. The objective of this study was to evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients currently in care on first-line ART for ≥ 6 months attending South African public healthcare facilities. We analysed electronic medical records of ART patients with a VL result on record who started ART between January 2004 and April 2016 from 271 public health facilities. We present descriptive and multivariable logistic regression for unsuppressed VL at last visit using a priori variables. We included 244,370 patients (69% female) on first-line ART in April 2016 for ≥ 6 months. Median age at ART start was 33 years (7% were < 15 years old). Median duration on ART was 3.7 years. Adjusting for other variables, factors associated with having an unsuppressed VL at the most recent visit among patients in care included: (1) < 15 years old at ART start (adjusted odds ratio [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR = 1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95% CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI = 1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved viral suppression, though men, youth/adolescents, patients with prior ART exposure, those with short duration of ART, and patients on TB treatment had increased odds of not achieving viral suppression. There is a need to develop and evaluate targeted interventions for ART patients in care who are at high risk of unsuppressed VL.

  1. The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.

    Science.gov (United States)

    Fuchs, Helmut; Sabrautzki, Sibylle; Przemeck, Gerhard K H; Leuchtenberger, Stefanie; Lorenz-Depiereux, Bettina; Becker, Lore; Rathkolb, Birgit; Horsch, Marion; Garrett, Lillian; Östereicher, Manuela A; Hans, Wolfgang; Abe, Koichiro; Sagawa, Nobuho; Rozman, Jan; Vargas-Panesso, Ingrid L; Sandholzer, Michael; Lisse, Thomas S; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Calzada-Wack, Julia; Ehrhard, Nicole; Elvert, Ralf; Gau, Christine; Hölter, Sabine M; Micklich, Katja; Moreth, Kristin; Prehn, Cornelia; Puk, Oliver; Racz, Ildiko; Stoeger, Claudia; Vernaleken, Alexandra; Michel, Dian; Diener, Susanne; Wieland, Thomas; Adamski, Jerzy; Bekeredjian, Raffi; Busch, Dirk H; Favor, John; Graw, Jochen; Klingenspor, Martin; Lengger, Christoph; Maier, Holger; Neff, Frauke; Ollert, Markus; Stoeger, Tobias; Yildirim, Ali Önder; Strom, Tim M; Zimmer, Andreas; Wolf, Eckhard; Wurst, Wolfgang; Klopstock, Thomas; Beckers, Johannes; Gailus-Durner, Valerie; Hrabé de Angelis, Martin

    2016-12-07

    The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein) family consists of three independent members, Scube1-3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3 N294K/N294K ), which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the German Mouse Clinic (GMC). Scube3 N294K/N294K mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB), associated with the chromosomal region of human SCUBE3 In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3 N294K/N294K mice. The Scube3 N294K/N294K mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function. Copyright © 2016 Fuchs et al.

  2. The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations

    Directory of Open Access Journals (Sweden)

    Helmut Fuchs

    2016-12-01

    Full Text Available The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein family consists of three independent members, Scube1–3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3N294K/N294K, which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the German Mouse Clinic (GMC. Scube3N294K/N294K mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB, associated with the chromosomal region of human SCUBE3. In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3N294K/N294K mice. The Scube3N294K/N294K mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function.

  3. Establishment of the first humpback whale fibroblast cell lines and their application in chemical risk assessment

    International Nuclear Information System (INIS)

    Burkard, Michael; Whitworth, Deanne; Schirmer, Kristin; Nash, Susan Bengtson

    2015-01-01

    Highlights: • We established and characterised the first humpback whale fibroblast cell lines. • Cell lines have a stable karyotype with 2n = 44. • Exposure to p,p′-DDE resulted in a concentration-dependent loss of cell viability. • p,p′-DDE sensitivity differed considerably from human fibroblasts. • Exposure to a whale blubber extract showed higher sensitivity than to p,p′-DDE alone. - Abstract: This paper reports the first successful derivation and characterization of humpback whale fibroblast cell lines. Primary fibroblasts were isolated from the dermal connective tissue of skin biopsies, cultured at 37 °C and 5% CO_2 in the standard mammalian medium DMEM/F12 supplemented with 10% fetal bovine serum (FBS). Of nine initial biopsies, two cell lines were established from two different animals and designated HuWa1 and HuWa2. The cells have a stable karyotype with 2n = 44, which has commonly been observed in other baleen whale species. Cells were verified as being fibroblasts based on their spindle-shaped morphology, adherence to plastic and positive immunoreaction to vimentin. Population doubling time was determined to be ∼41 h and cells were successfully cryopreserved and thawed. To date, HuWa1 cells have been propagated 30 times. Cells proliferate at the tested temperatures, 30, 33.5 and 37 °C, but show the highest rate of proliferation at 37 °C. Short-term exposure to para,para′-dichlorodiphenyldichloroethylene (p,p′-DDE), a priority compound accumulating in southern hemisphere humpback whales, resulted in a concentration-dependent loss of cell viability. The effective concentration which caused a 50% reduction in HuWa1 cell viability (EC_5_0 value) was approximately six times greater than the EC_5_0 value for the same chemical measured with human dermal fibroblasts. HuWa1 exposed to a natural, p,p′-DDE-containing, chemical mixture extracted from whale blubber showed distinctively higher sensitivity than to p,p′-DDE alone. Thus, we

  4. Establishment of the first humpback whale fibroblast cell lines and their application in chemical risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Burkard, Michael, E-mail: Michael.burkard@eawag.ch [Griffith University, Environmental Futures Research Institute, Southern Ocean Persistent Organic Pollutants Program, Brisbane, QLD (Australia); Eawag, Swiss Federal Institute of Technology, Dübendorf (Switzerland); Whitworth, Deanne [The University of Queensland, School of Veterinary Science, Gatton, QLD (Australia); Schirmer, Kristin [Eawag, Swiss Federal Institute of Technology, Dübendorf (Switzerland); ETH Zürich, Institute of Biogechemistry and Pollutant Dynamics, Zürich (Switzerland); EPF Lausanne, School of Architecture, Civil and Environmental Engineering, Lausanne (Switzerland); Nash, Susan Bengtson [Griffith University, Environmental Futures Research Institute, Southern Ocean Persistent Organic Pollutants Program, Brisbane, QLD (Australia)

    2015-10-15

    Highlights: • We established and characterised the first humpback whale fibroblast cell lines. • Cell lines have a stable karyotype with 2n = 44. • Exposure to p,p′-DDE resulted in a concentration-dependent loss of cell viability. • p,p′-DDE sensitivity differed considerably from human fibroblasts. • Exposure to a whale blubber extract showed higher sensitivity than to p,p′-DDE alone. - Abstract: This paper reports the first successful derivation and characterization of humpback whale fibroblast cell lines. Primary fibroblasts were isolated from the dermal connective tissue of skin biopsies, cultured at 37 °C and 5% CO{sub 2} in the standard mammalian medium DMEM/F12 supplemented with 10% fetal bovine serum (FBS). Of nine initial biopsies, two cell lines were established from two different animals and designated HuWa1 and HuWa2. The cells have a stable karyotype with 2n = 44, which has commonly been observed in other baleen whale species. Cells were verified as being fibroblasts based on their spindle-shaped morphology, adherence to plastic and positive immunoreaction to vimentin. Population doubling time was determined to be ∼41 h and cells were successfully cryopreserved and thawed. To date, HuWa1 cells have been propagated 30 times. Cells proliferate at the tested temperatures, 30, 33.5 and 37 °C, but show the highest rate of proliferation at 37 °C. Short-term exposure to para,para′-dichlorodiphenyldichloroethylene (p,p′-DDE), a priority compound accumulating in southern hemisphere humpback whales, resulted in a concentration-dependent loss of cell viability. The effective concentration which caused a 50% reduction in HuWa1 cell viability (EC{sub 50} value) was approximately six times greater than the EC{sub 50} value for the same chemical measured with human dermal fibroblasts. HuWa1 exposed to a natural, p,p′-DDE-containing, chemical mixture extracted from whale blubber showed distinctively higher sensitivity than to p,p′-DDE alone

  5. Can a surgery-first orthognathic approach reduce the total treatment time?

    Science.gov (United States)

    Jeong, Woo Shik; Choi, Jong Woo; Kim, Do Yeon; Lee, Jang Yeol; Kwon, Soon Man

    2017-04-01

    Although pre-surgical orthodontic treatment has been accepted as a necessary process for stable orthognathic correction in the traditional orthognathic approach, recent advances in the application of miniscrews and in the pre-surgical simulation of orthodontic management using dental models have shown that it is possible to perform a surgery-first orthognathic approach without pre-surgical orthodontic treatment. This prospective study investigated the surgical outcomes of patients with diagnosed skeletal class III dentofacial deformities who underwent orthognathic surgery between December 2007 and December 2014. Cephalometric landmark data for patients undergoing the surgery-first approach were analyzed in terms of postoperative changes in vertical and horizontal skeletal pattern, dental pattern, and soft tissue profile. Forty-five consecutive Asian patients with skeletal class III dentofacial deformities who underwent surgery-first orthognathic surgery and 52 patients who underwent conventional two-jaw orthognathic surgery were included. The analysis revealed that the total treatment period for the surgery-first approach averaged 14.6 months, compared with 22.0 months for the orthodontics-first approach. Comparisons between the immediate postoperative and preoperative and between the postoperative and immediate postoperative cephalometric data revealed factors that correlated with the total treatment duration. The surgery-first orthognathic approach can dramatically reduce the total treatment time, with no major complications. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. 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.

  7. Posttraumatic stress disorder (PTSD) Treatment

    Science.gov (United States)

    ... does the current evidence say about treatment for PTSD? Read Psych Health Evidence Briefs , which summarize available ... first-line and emerging PTSD treatments. Psychotherapy for PTSD According to the VA/DoD Clinical Practice Guideline ...

  8. Multicenter Phase II Study with Weekly Bendamustine and Paclitaxel as First- or Later-Line Therapy in Patients with Metastatic Breast Cancer: RiTa II Trial.

    Science.gov (United States)

    Loibl, Sibylle; Doering, Gabriele; Müller, Lothar; Grote-Metke, Albert; Müller, Roberto; Tomé, Oliver; Wiest, Wolfgang; Maisch, Andrea; Nekljudova, Valentina; von Minckwitz, Gunter

    2011-12-01

    The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2) with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9-22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.

  9. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

    Science.gov (United States)

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

  10. Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies.

    Science.gov (United States)

    Boeckx, Nele; Koukakis, Reija; Op de Beeck, Ken; Rolfo, Christian; Van Camp, Guy; Siena, Salvatore; Tabernero, Josep; Douillard, Jean-Yves; André, Thierry; Peeters, Marc

    2018-03-08

    The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC. RAS WT data (n = 483) from 2 randomized phase III panitumumab trials (ClinicalTrials.gov identifiers, NCT00339183 and NCT00113763) were analyzed for treatment outcomes stratified by tumor location. The second analysis assessed the effect of tumor location in RAS MT patients (n = 1205) from 4 panitumumab studies (ClinicalTrials.gov identifiers, NCT00364013, NCT00819780, NCT00339183, and NCT00113763). Primary tumors located in the cecum to transverse colon were coded as right-sided; those located from the splenic flexure to the rectum were coded as left-sided. Of all patients, the tumor location was ascertained for 83% to 88%; 71% to 77% of patients had left-sided tumors. RAS WT patients with right-sided tumors did worse for all efficacy parameters compared with those with left-sided tumors. The patients with left-sided tumors had better outcomes with panitumumab than with the comparator treatment. Because of the low patient numbers, no conclusions could be drawn for right-sided mCRC. The prognostic effect of tumor location on survival was unclear for RAS MT patients. These retrospective analyses have confirmed that RAS WT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RAS WT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Osteoporosis treatment

    DEFF Research Database (Denmark)

    Pazianas, Michael; Abrahamsen, Bo

    2016-01-01

    The findings of the Women's Health Initiative study in 2002 marginalized the use of hormone replacement therapy and established bisphosphonates as the first line of treatment for osteoporosis. Denosumab could be used in selected patients. Although bisphosphonates only maintain the structure of bone...... to their benefits/harm ratio. Treatment of osteoporosis is a long process, and many patients will require treatment with more than one type of drug over their lifetime....

  12. Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation.

    Science.gov (United States)

    Trevisani, Franco; Brandi, Giovanni; Garuti, Francesca; Barbera, Maria Aurelia; Tortora, Raffaella; Casadei Gardini, Andrea; Granito, Alessandro; Tovoli, Francesco; De Lorenzo, Stefania; Inghilesi, Andrea Lorenzo; Foschi, Francesco Giuseppe; Bernardi, Mauro; Marra, Fabio; Sacco, Rodolfo; Di Costanzo, Giovan Giuseppe

    2018-02-01

    Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [PSS: 17.3 (10.5-24.1) vs. 7.8 (5.2-10.1) months, (p = 0.035)]. Treatment toxicity was low and easily manageable with dose modulation. MC may be an efficient and safe second-line systemic therapy for HCC patients who discontinued sorafenib for toxicity or tumor progression.

  13. Patterns of HIV-1 Drug Resistance After First-Line Antiretroviral Therapy (ART) Failure in 6 Sub-Saharan African Countries: Implications for Second-Line ART Strategies

    NARCIS (Netherlands)

    Hamers, Raph L.; Sigaloff, Kim C. E.; Wensing, Annemarie M.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S.; Rinke de Wit, Tobias F.; Schuurman, Rob; Siwale, M.; Njovu, C.; Labib, M.; Menke, J.; Botes, M. E.; Conradie, F.; Ive, P.; Sanne, I.; Wallis, C. L.; Letsoalo, E.; Stevens, W. S.; Hardman, M.; Wellington, M.; Luthy, R.; Mandaliya, K.; Abdallah, S.; Jao, I.; Dolan, M.; Namayanja, G.; Nakatudde, L.; Nankya, I.; Kiconco, M.; Abwola, M.; Mugyenyi, P.; Osibogun, A.; Akanmu, S.; Schuurman, R.; Wensing, A. M.; Straatsma, E.; Wit, F. W.; Dekker, J.; van Vugt, M.; Lange, J. M.

    2012-01-01

    Background. Human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy (ART). This cohort study examined patterns of drug-resistance mutations (DRMs) in individuals with virological failure on first-line ART at 13 clinical sites in 6 African

  14. Label-free LC-MS analysis of HER2+ breast cancer cell line response to HER2 inhibitor treatment.

    Science.gov (United States)

    Di Luca, Alessio; Henry, Michael; Meleady, Paula; O'Connor, Robert

    2015-08-04

    Human epidermal growth-factor receptor (HER)-2 is overexpressed in 25 % of breast-cancers and is associated with an aggressive form of the disease with significantly shortened disease free and overall survival. In recent years, the use of HER2-targeted therapies, monoclonal-antibodies and small molecule tyrosine-kinase inhibitors has significantly improved the clinical outcome for HER2-positive breast-cancer patients. However, only a fraction of HER2-amplified patients will respond to therapy and the use of these treatments is often limited by tumour drug insensitivity or resistance and drug toxicities. Currently there is no way to identify likely responders or rational combinations with the potential to improve HER2-focussed treatment outcome. In order to further understand the molecular mechanisms of treatment-response with HER2-inhibitors, we used a highly-optimised and reproducible quantitative label-free LC-MS strategy to characterize the proteomes of HER2-overexpressing breast-cancer cell-lines (SKBR3, BT474 and HCC1954) in response to drug-treatment with HER2-inhibitors (lapatinib, neratinib or afatinib). Following 12 ours treatment with different HER2-inhibitors in the BT474 cell-line; compared to the untreated cells, 16 proteins changed significantly in abundance following lapatinib treatment (1 μM), 21 proteins changed significantly following neratinib treatment (150 nM) and 38 proteins changed significantly following afatinib treatment (150 nM). Whereas following 24 hours treatment with neratinib (200 nM) 46 proteins changed significantly in abundance in the HCC1954 cell-line and 23 proteins in the SKBR3 cell-line compared to the untreated cells. Analysing the data we found that, proteins like trifunctional-enzyme subunit-alpha, mitochondrial; heterogeneous nuclear ribonucleoprotein-R and lamina-associated polypeptide 2, isoform alpha were up-regulated whereas heat shock cognate 71 kDa protein was down-regulated in 3 or more comparisons. This proteomic

  15. Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy?

    Science.gov (United States)

    Gatto, Federico; Grasso, Ludovica F; Nazzari, Elena; Cuny, Thomas; Anania, Pasquale; Di Somma, Carolina; Colao, Annamaria; Zona, Gianluigi; Weryha, Georges; Pivonello, Rosario; Ferone, Diego

    2015-10-01

    Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications. We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27-61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2-4.2 mIU/L), with median fT4 2.52 ng/dL (0.9-1.7 ng/dL). Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease -72%), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach. Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50%). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.

  16. Case Report of First Angiography-Based On-Line FFR Assessment during Coronary Catheterization.

    Science.gov (United States)

    Kornowski, Ran; Vaknin-Assa, Hana

    2017-01-01

    Fractional flow reserve (FFR), an index of the hemodynamic severity of coronary stenoses, is derived from hyperemic pressure measurements and requires a pressure-monitoring guide wire and hyperemic stimulus. Although it has become the standard of reference for decision-making regarding coronary revascularization, the procedure remains underutilized due to its invasive nature. FFR angio is a novel technology that uses the patient's hemodynamic data and routine angiograms to generate a complete three-dimensional coronary tree, with color-coded display of the FFR values at each point along the vessels. After being proven to be as accurate as invasive FFR measurements in an off-line study, this case report presents the first on-line application of the system in the catheterization lab. Here too, a high concordance between FFR angio and invasive FFR was observed. In light of the demonstrated capabilities of the FFR angio system, it should emerge as an important tool for clinical decision-making regarding revascularization in patients with coronary artery disease.

  17. Case Report of First Angiography-Based On-Line FFR Assessment during Coronary Catheterization

    Directory of Open Access Journals (Sweden)

    Ran Kornowski

    2017-01-01

    Full Text Available Fractional flow reserve (FFR, an index of the hemodynamic severity of coronary stenoses, is derived from hyperemic pressure measurements and requires a pressure-monitoring guide wire and hyperemic stimulus. Although it has become the standard of reference for decision-making regarding coronary revascularization, the procedure remains underutilized due to its invasive nature. FFRangio is a novel technology that uses the patient’s hemodynamic data and routine angiograms to generate a complete three-dimensional coronary tree, with color-coded display of the FFR values at each point along the vessels. After being proven to be as accurate as invasive FFR measurements in an off-line study, this case report presents the first on-line application of the system in the catheterization lab. Here too, a high concordance between FFRangio and invasive FFR was observed. In light of the demonstrated capabilities of the FFRangio system, it should emerge as an important tool for clinical decision-making regarding revascularization in patients with coronary artery disease.

  18. Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

    Science.gov (United States)

    Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

    2012-01-01

    Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

  19. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  20. USE OF DIMETHYL FUMARATE IN THE TREATMENT OF MULTIPLE SCLEROSIS: CLINICAL AND ECONOMIC ANALYSIS

    Directory of Open Access Journals (Sweden)

    V. R. Mkrtchyan

    2016-01-01

    Full Text Available The paper presents a review of an update on the comparative pharmacoeconomic analysis of using dimethyl fumarate in the treatment of multiple sclerosis (MS in European countries. A pharmacoeconomic evaluation was made to study the use of first-line oral dimethyl fumarate versus another first-line oral teriflunomide in the treatment of MS in the Russian Federation (for 1 year and second-line natalizumab and fingolimod. Among first-line oral drugs, dimethyl fumarate was shown to be superior to teriflunomide in a cost-effectiveness ratio and to be slightly ahead of the MS-modifying drugs (MSMDs  and the second-line drugs natalizumab and fingolimod. According to clinical and economic indicators, dimethyl fumarate is the drug of choise among other MSMDs in the treatment of MS.

  1. Morphine as first medication for treatment of cancer pain

    Directory of Open Access Journals (Sweden)

    Beatriz C. Nunes

    2014-07-01

    Full Text Available BACKGROUND AND OBJECTIVES: the medications used according to the recommendation of the World Health Organization do not promote pain relief in a number of patients with cancer pain. The aim of this study was to evaluate the use of morphine as first medication for the treatment of moderate cancer pain in patients with advanced and/or metastatic disease, as an option to the recommendations of the World Health Organization analgesic ladder. METHOD: sixty patients without opioid therapy, with >18 years of age, were randomized into two groups. G1 patients received medication according to the analgesic ladder and started treatment with non-opioids in the first, weak opioids in the second, and strong opioids in the third step; G2 patients received morphine as first analgesic medication. The efficacy and tolerability of initial use of morphine were evaluated every two weeks for three months. RESULTS: the groups were similar with respect to demographic data. There was no significant difference between the groups regarding pain intensity, quality of life, physical capacity, satisfaction with treatment, need for complementation and dose of morphine. In G1 there was a higher incidence of nausea (p = 0.0088, drowsiness (p = 0.0005, constipation (p = 0.0071 and dizziness (p = 0.0376 in the second visit and drowsiness (p = 0.05 in the third. CONCLUSIONS: the use of morphine as first medication for pain treatment did not promote better analgesic effect than the ladder recommended by World Health Organization, with higher incidence of adverse effects.

  2. Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy.

    Science.gov (United States)

    Michl, M; Koch, J; Laubender, R P; Modest, D P; Giessen, C; Schulz, Ch; Heinemann, V

    2014-10-01

    In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in

  3. 30 CFR 50.20-3 - Criteria-Differences between medical treatment and first aid.

    Science.gov (United States)

    2010-07-01

    ... and first aid. 50.20-3 Section 50.20-3 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... first aid. (a) Medical treatment includes, but is not limited to, the suturing of any wound, treatment... treatment. Tetanus and flu shots are considered preventative in nature. First aid includes any one-time...

  4. 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

    International Nuclear Information System (INIS)

    Thaler, Josef; Köhne, Claus-Henning; Karthaus, Meinolf; Mineur, Laurent; Greil, Richard; Letocha, Henry; Hofheinz, Ralf; Fernebro, Eva; Gamelin, Erick; Baños, Ana

    2012-01-01

    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. 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. 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. First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity. ClinicalTrials.gov NCT00508404

  5. 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

  6. Evaluation of biocorrosion of pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Ferris, F G

    1989-03-31

    A study was conducted to evaluate the effects of an input of viable planktonic bacteria on the development of corrodent microbial biofilms and biocide performance at the Wainwright (Alberta) heavy oil field water injection field test facility. Data were collected from 5 separate slipstreams in a common loop off the main water injection line. Attached microbial populations were allowed to develop during the first 34 weeks of monitoring. Then 2 lines were treated with a combination of ultraviolet (UV) radiation, to disinfect input streams, and a cocodiamine biocide. A third was treated with biocide alone; the remaining lines were the controls. In the first 4 weeks, a near-exponential increase in viable counts of attached sulfate-reducing bacteria (SRB) was observed. After treatment began, biocide alone induced a steady decline in SRB counts. UV disinfection of input water did not significantly enhance biocide performance; turnover rates of {sup 35}S-labelled sulfate to sulfide were decreased. Adding nitrate and methanol did not affect SRB activity levels in lab assays. Comparable populations of SRB developed on carbon steel and plastic sample coupons. Acid-producing bacteria (APB) were also present on both types of coupons, but at much lower levels than SRB. The APB counts decreased along with SRB counts during biocide treatment. Biocide treatment maintained general corrosion and pitting tendency rates at reduced levels compared to the control. A slight trend towards higher corrosion rates with increasing numbers of SRB was observed. Normalization of of activity by viable counts gave a bimodal distribution of data, suggesting that higher corrosion rates might be associated with SRB which utilize substrates other than lactate for their source of energy and carbon. 20 refs., 20 figs.

  7. Gamma Knife radiosurgery for the treatment of intracranial dural arteriovenous fistulas

    Science.gov (United States)

    Dmytriw, Adam A; Schwartz, Michael L; Cusimano, Michael D; Mendes Pereira, Vitor; Krings, Timo; Tymianski, Michael; Radovanovic, Ivan

    2016-01-01

    Background Intracranial dural arteriovenous fistulae (DAVF) may present a treatment challenge. Endovascular embolization is in most cases the first line of treatment but does not always achieve cure. Gamma Knife (GK) radiosurgery represents an alternative treatment option, and the purpose of this study was to further evaluate its utility. Methods We reviewed all cases of DAVF treated between 2009 and 2016 at our institution with GK radiosurgery independently, or following failed/refused endovascular or surgical management. Patients’ clinical files, radiological images, catheter angiograms, and surgical DAVF disconnection reports were retrospectively reviewed. Results Sixteen DAVF (14 patients) treated by GK radiosurgery were identified. Eleven fistulae were aggressive and five were benign. Marginal doses ranged from 15 to 25 Gy. Target volumes ranged from 0.04 to 4.47 cm3. In all symptomatic patients, GK treatment resulted in symptom palliation. In 13/15 lesions, cure of symptoms (86.0%) was reported. One lesion was asymptomatic. Angiographic cure was achieved in eight cases (50%), small residual DAVF occurred in four, and four were unchanged. One patient developed headache that resolved at one year. No hemorrhage occurred during the follow-up period. There was no significant association between Borden type and cure rate. Prior failed endovascular treatment and small target volume were associated with lower rates of cure. Conclusions Stereotactic radiosurgery is viable treatment for DAVF. It is very effective in palliating symptoms as a de novo approach or adjunctive to endovascular therapy. In our experience it is only somewhat effective in achieving complete angiographic cure. PMID:28156167

  8. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection.

    Science.gov (United States)

    Gisbert, Javier P; Molina-Infante, Javier; Marin, Alicia C; Vinagre, Gemma; Barrio, Jesus; McNicholl, Adrian Gerald

    2013-06-01

    Non-bismuth quadruple "sequential" and "concomitant" regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. prospective multicenter study. in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. eradication was confirmed with (13)C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple "sequential" or "concomitant" treatment failure.

  9. A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Rodenburg, C. J.; Cats, A.; Creemers, G. J.; Schrama, J. G.; Erdkamp, F. L. G.; Vos, A. H.; Mol, L.; Antonini, N. F.; Punt, C. J. A.

    2008-01-01

    Targeting the vascular endothelial growth factor or the epidermal growth factor receptor (EGFR) has shown efficacy in advanced colorectal cancer (ACC), but no data are available on the combination of these strategies with chemotherapy in the first-line treatment. The CAIRO2 study evaluates the

  10. FIRST DETECTION OF NEAR-INFRARED LINE EMISSION FROM ORGANICS IN YOUNG CIRCUMSTELLAR DISKS

    Energy Technology Data Exchange (ETDEWEB)

    Mandell, Avi M.; Mumma, Michael J.; Villanueva, Geronimo [Solar System Exploration Division, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Bast, Jeanette; Van Dishoeck, Ewine F. [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Blake, Geoffrey A. [California Institute of Technology, Division of Geological and Planetary Sciences, MS 150-21, Pasadena, CA 91125 (United States); Salyk, Colette, E-mail: Avi.Mandell@nasa.gov [Department of Astronomy, University of Texas, Austin, TX 78712 (United States)

    2012-03-10

    We present an analysis of high-resolution spectroscopy of several bright T Tauri stars using the CRIRES spectrograph on the Very Large Telescope and NIRSPEC spectrograph on the Keck Telescope, revealing the first detections of emission from HCN and C{sub 2}H{sub 2} in circumstellar disks at near-infrared wavelengths. Using advanced data reduction techniques, we achieve a dynamic range with respect to the disk continuum of {approx}500 at 3 {mu}m, revealing multiple emission features of H{sub 2}O, OH, HCN, and C{sub 2}H{sub 2}. We also present stringent upper limits for two other molecules thought to be abundant in the inner disk, CH{sub 4} and NH{sub 3}. Line profiles for the different detected molecules are broad but centrally peaked in most cases, even for disks with previously determined inclinations of greater than 20 Degree-Sign , suggesting that the emission has both a Keplerian and non-Keplerian component as observed previously for CO emission. We apply two different modeling strategies to constrain the molecular abundances and temperatures: we use a simplified single-temperature local thermal equilibrium (LTE) slab model with a Gaussian line profile to make line identifications and determine a best-fit temperature and initial abundance ratios, and we compare these values with constraints derived from a detailed disk radiative transfer model assuming LTE excitation but utilizing a realistic temperature and density structure. Abundance ratios from both sets of models are consistent with each other and consistent with expected values from theoretical chemical models, and analysis of the line shapes suggests that the molecular emission originates from within a narrow region in the inner disk (R < 1 AU).

  11. 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

  12. First light - II. Emission line extinction, population III stars, and X-ray binaries

    Science.gov (United States)

    Barrow, Kirk S. S.; Wise, John H.; Aykutalp, Aycin; O'Shea, Brian W.; Norman, Michael L.; Xu, Hao

    2018-02-01

    We produce synthetic spectra and observations for metal-free stellar populations and high-mass X-ray binaries in the Renaissance Simulations at a redshift of 15. We extend our methodology from the first paper in the series by modelling the production and extinction of emission lines throughout a dusty and metal-enriched interstellar and circum-galactic media extracted from the simulation, using a Monte Carlo calculation. To capture the impact of high-energy photons, we include all frequencies from hard X-ray to far-infrared with enough frequency resolution to discern line emission and absorption profiles. The most common lines in our sample in order of their rate of occurrence are Ly α, the C IV λλ1548, 1551 doublet, H α, and the Ca II λλλ8498, 8542, 8662 triplet. The best scenario for a direct observation of a metal-free stellar population is a merger between two Population III Galaxies. In mergers between metal-enriched and metal-free stellar populations, some characteristics may be inferred indirectly. Single Population III galaxies are too dim to be observed photometrically at z = 15. Ly α emission is discernible by JWST as an increase in J200w - J277w colour off the intrinsic stellar tracks. Observations of metal-free stars will be difficult, though not impossible, with the next generation of space telescopes.

  13. Selection of viable cell subpopulations from murine tumours using FACS

    International Nuclear Information System (INIS)

    Chaplin, D.J.; Durand, R.E.; Olive, P.L.

    1985-01-01

    The authors developed a technique which enables isolation of viable tumour cells subpopulation as a function of their distance from the blood supply. The basis for this separation procedure is that the fluorochrome, Hoechst 33342, as a result of its high avidity for cellular DNA, exhibits a marked diffusion/consumption gradient when it has to pass through several cell layers. As a result intravenous injection of Hoechst 33342 into tumour bearing animals, results in a heterogeneous straining pattern within the tumour with cells close to blood vessels being brightly fluorescent while those more distant are less intensely stained. Since these differences in staining intensity persist after tumour disaggregation, cells can be sorted into subpopulations on the basis of their fluorescence intensity using a fluorescence activated cell sorter. This technique offers the unique possibility of identifying the location of those cell subpopulations resistant to treatment with either radiation or chemotherapeutic drugs

  14. Prognostic risk stratification derived from individual patient level data for men with advanced penile squamous cell carcinoma receiving first-line systemic therapy.

    Science.gov (United States)

    Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

    2014-05-01

    Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (Pstatistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including

  15. Plant Line Trial Evaluation of Viable Non-Chromium Passivation Systems for Electrolytin Tinplate, ETP (TRP 9911)

    Energy Technology Data Exchange (ETDEWEB)

    John A. Sinsel

    2003-06-30

    Plant trial evaluations have been completed for two zirconium-based, non-chromium passivation systems previously identified as possible alternatives to cathodic dichromate (CDC) passivation for electrolytic tinplate (ETP). These trials were done on a commercial electrolytic tin plating line at Weirton Steel and extensive evaluations of the materials resulting from these trials have been completed. All this was accomplished as a collaborative effort under the AISI Technology Roadmap Program and was executed by seven North American Tin Mill Products producers [Bethlehem Steel (now acquired by International Steel Group (ISG)), Dofasco Inc., National Steel (now acquired by U.S. Steel), U.S. Steel, USS-Posco, Weirton Steel, and Wheeling-Pittsburgh Steel] with funding partially from the Department of Energy (DOE) and partially on an equal cost sharing basis among project participants. The initial phases of this project involved optimization of application procedures for the non-chromium systems in the laboratories at Bethlehem Steel and Betz Dearborn followed by extensive testing with various lacquer formulations and food simulants in the laboratories at Valspar and PPG. Work was also completed at Dofasco and Weirton Steel to develop methods to prevent precipitation of insoluble solids as a function of time from the zirconate system. The results of this testing indicated that sulfide staining characteristics for the non-chromium passivation systems could be minimized but not totally eliminated and neither system was found to perform quite as good, in this respect, as the standard CDC system. As for the stability of zirconate treatment, a method was developed to stabilize this system for a sufficient period of time to conduct plant trial evaluations but, working with a major supplier of zirconium orthosulfate, a method for long term stabilization is still under development.

  16. Association of viable Mycobacterium leprae with Type 1 reaction in leprosy.

    Science.gov (United States)

    Save, Mrudula Prakash; Dighe, Anju Rajaram; Natrajan, Mohan; Shetty, Vanaja Prabhakaran

    2016-03-01

    The working hypothesis is that, viable Mycobacterium leprae (M. leprae) play a crucial role in the precipitation of Type 1 reaction (T1R) in leprosy. A total of 165 new multibacillary patients were studied. To demonstrate presence of viable M. leprae in reactional lesion (T1R+), three tests were used concurrently viz. growth in the mouse foot pad (MFP), immunohistochemical detection of M. leprae secretory protein Ag85, and 16s rRNA--using in situ RT-PCR. Mirror biopsies and non reactional lesions served as controls (T1R-). A significantly higher proportion of lesion biopsy homogenates obtained at onset, from T1R(+) cases have shown unequivocal growth in MFP, proving the presence of viable bacteria, as compared to T1R(-) (P leprae is a component/prerequisite and the secretory protein Ag 85, might be the trigger for precipitation of T1R.

  17. Systematic review: Coca-Cola can effectively dissolve gastric phytobezoars as a first-line treatment.

    Science.gov (United States)

    Ladas, S D; Kamberoglou, D; Karamanolis, G; Vlachogiannakos, J; Zouboulis-Vafiadis, I

    2013-01-01

    Gastric phytobezoars represent the most common bezoars in patients with poor gastric motility. A variety of dissolution therapies and endoscopic fragmentation techniques have been evaluated as conservative treatment so as to avoid surgery. To investigate the effectiveness of Coca-Cola for gastric phytobezoars dissolution. We performed a systematic search to identify publications on gastric phytobezoars to assess the efficacy of Coca-Cola as a dissolution therapy. Diospyrobezoars, formed after persimmon ingestion, are a distinct type of phytobezoars characterized by their hard consistency. Thus, these two subgroups of bezoars were compared in terms of successful dissolution. Over a 10-year period (2002-2012), 24 papers including 46 patients have been published. In 91.3% of the cases, phytobezoar resolution with Coca-Cola administration was successful, either as a single treatment (50%) or combined with further endoscopic techniques, whereas only 4 patients underwent surgery. Phytobezoars were more likely to dissolve after initial attempt with Coca-Cola compared with diospyrobezoars (60.6% vs. 23%, P = 0.022). Coca-Cola alone is effective in gastric phytobezoar dissolution in half of the cases and, combined with additional endoscopic methods, is successful in more than 90% of them. © 2012 Blackwell Publishing Ltd.

  18. 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.

  19. On- and off-line monitoring of ion beam treatment

    Energy Technology Data Exchange (ETDEWEB)

    Parodi, Katia, E-mail: katia.parodi@lmu.de

    2016-02-11

    Ion beam therapy is an emerging modality for high precision radiation treatment of cancer. In comparison to conventional radiation sources (photons, electrons), ion beams feature major dosimetric advantages due to their finite range with a localized dose deposition maximum, the Bragg peak, which can be selectively adjusted in depth. However, due to several sources of treatment uncertainties, full exploitation of these dosimetric advantages in clinical practice would require the possibility to visualize the stopping position of the ions in vivo, ideally in real-time. To this aim, different imaging methods have been proposed and investigated, either pre-clinically or even clinically, based on the detection of prompt or delayed radiation following nuclear interaction of the beam with the irradiated tissue. However, the chosen or ad-hoc developed instrumentation has often relied on technologies originally conceived for different applications, thus compromising on the achievable performances for the sake of cost-effectiveness. This contribution will review major examples of used instrumentation and related performances, identifying the most promising detector developments for next generation devices especially dedicated to on-line monitoring of ion beam treatment. Moreover, it will propose an original combination of different techniques in a hybrid detection scheme, aiming to make the most of complementary imaging methods and open new perspectives of image guidance for improved precision of ion beam therapy.

  20. Sycamore produces viable seed after six years

    Science.gov (United States)

    A. F. Ike

    1966-01-01

    In the early stages of any tree improvement program it is desirable to know how soon progenies of selected parents can themselves be included in a breeding program. How soon will they produce viable pollen and seed? In the case of sycamore (Platanus occidentalis L.), the information is meager: the Woody- Plant Seed Manual lists the minimum commercial seedbearing age...