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Sample records for second-line quadruple therapy

  1. Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection

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    Guang-Hong Jheng

    2015-01-01

    Full Text Available The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or “concomitant therapy” is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%. The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, P=0.02, but only seven patients (11.5% experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries.

  2. Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments.

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    Gisbert, J P; Romano, M; Gravina, A G; Solís-Muñoz, P; Bermejo, F; Molina-Infante, J; Castro-Fernández, M; Ortuño, J; Lucendo, A J; Herranz, M; Modolell, I; Del Castillo, F; Gómez, J; Barrio, J; Velayos, B; Gómez, B; Domínguez, J L; Miranda, A; Martorano, M; Algaba, A; Pabón, M; Angueira, T; Fernández-Salazar, L; Federico, A; Marín, A C; McNicholl, A G

    2015-04-01

    The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed. © 2015 John Wiley & Sons Ltd.

  3. Efficacy and safety of sequential versus quadruple therapy as second-line treatment for helicobacter pylori infection-A randomized controlled trial.

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    Daniela Munteanu

    Full Text Available Quadruple therapy is recommended as second-line treatment for Helicobacter pylori eradication failure. However, high cost, multiple side effects, and low adherence rates are major drawbacks to its routine use. Our aim was to compare the efficacy and safety of sequential versus quadruple regimens as second line treatment for persistent Helicobacter pylori infection.Prospective, randomized, open label trial was conducted at a large academic, tertiary care center in Israel. Patients who previously failed a standard triple treatment eradication course were randomly assigned (1:1 to receive a 10-day sequential therapy course, or a 14-day quadruple regimen. Compliance and adverse events were evaluated by telephone questionnaires. The primary endpoint for analysis was the rate of Helicobacter pylori eradication as defined by either a negative 13C-urea breath-test, or stool antigen test, 4-16 weeks after treatment assessed under the non-inferiority hypothesis. The trial was terminated prematurely due to low recruitment rates. See S1 Checklist for CONSORT checklist.One hundred and one patients were randomized. Per modified intention-to-treat analysis, eradication rate was 49% in the sequential versus 42.5% in the quadruple regimen group (p-value for non-inferiority 0.02. Forty-two (84.0% versus 33 (64.7% patients completed treatment in the sequential and quadruple groups respectively (p 0.027. Gastrointestinal side effects were more common in the quadruple regimen group.Sequential treatment when used as a second line regimen, was non-inferior to the standard of care quadruple regimen in achieving Helicobacter pylori eradication, and was associated with better compliance and fewer adverse effects. Both treatment protocols failed to show an adequate eradication rate in the population of Southern Israel.ClinicalTrials.gov NCT01481844.

  4. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection.

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    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.

  5. Second-Line Therapy for Advanced NSCLC.

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    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.

  6. Second-line systemic therapy for metastatic colorectal cancer.

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    Mocellin, Simone; Baretta, Zora; Roqué I Figuls, Marta; Solà, Ivan; Martin-Richard, Marta; Hallum, Sara; Bonfill Cosp, Xavier

    2017-01-27

    The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions. Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy. Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI). Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2

  7. Quadruple H therapy for vasospasm

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    Walid M

    2009-01-01

    Full Text Available Triple H therapy has been enthusiastically used to increase cerebral blood flow in cases of vasospasm. Nevertheless, the oxygen-carrying capacity of the blood is lowered with this treatment. This side effect can theoretically be partially corrected using hyperbaric oxygen therapy (HBO which appears to be the missing ring in the above therapeutic regimen. We conducted a review of of the available evidence regarding the beneficial effects of HBO in preventing postoperative ischemic complications due to vasospasm after surgery on ruptured cerebral aneurysms and the rationale for including HBO into the standards of care of these difficult patients.

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

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    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

  9. Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

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    Gisbert, Javier P; Pérez-Aisa, Angeles; Bermejo, Fernando; Castro-Fernández, Manuel; Almela, Pedro; Barrio, Jesús; Cosme, Angel; Modolell, Inés; Bory, Felipe; Fernández-Bermejo, Miguel; Rodrigo, Luis; Ortuño, Jesús; Sánchez-Pobre, Pilar; Khorrami, Sam; Franco, Alejandro; Tomas, Albert; Guerra, Iván; Lamas, Eloisa; Ponce, Julio; Calvet, Xavier

    2013-02-01

    Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Prospective multicenter study. In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

  10. Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

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    Maria-Virginia Bluthgen

    2015-12-01

    Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

  11. Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma.

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    Parikh, Neehar D; Singal, Amit G; Hutton, David W

    2017-10-01

    Regorafenib, a multikinase inhibitor, has demonstrated prolonged survival by 2.8 months as a second-line agent in patients with hepatocellular carcinoma (HCC) who progress on sorafenib therapy. The objective of the current study was to examine the cost effectiveness of regorafenib for the treatment of HCC. The authors constructed a Markov simulation model of patients with unresectable HCC and Child-Pugh A cirrhosis who received treatment with regorafenib versus best supportive care. Model inputs for regorafenib effectiveness and rates of adverse events in patients with HCC were based on published clinical trial data and literature review. Quality-adjusted life years (QALYs) were calculated along with the incremental cost-effectiveness ratio (ICER) of regorafenib therapy. One-way sensitivity analyses also were conducted simultaneously on all model parameters and on various Monte-Carlo simulation parameters, and the regorafenib cost threshold at which cost effectiveness would be achieved was determined. Regorafenib provided an increase of 0.18 QALYs at a cost of $47,112. The ICER for regorafenib, compared with best supportive care, was $224,362. In 1-way sensitivity analyses, there were no scenarios in which regorafenib was cost effective. In cost threshold analysis, regorafenib would have to be priced at or below $67 per pill to be cost effective at an ICER of $100,000. Regorafenib is not cost effective as a second-line agent in the treatment of HCC, with a marginal increase in QALYs at a high cost. Lowering the cost of regorafenib or improving the selection of patients who can achieve maximal survival benefit would improve its value as a second-line treatment option for patients with HCC. Cancer 2017;123:3725-3731. © 2017 American Cancer Society. © 2017 American Cancer Society.

  12. A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

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    Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

    2017-07-01

    It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

  13. Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa

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    W Barnett

    2013-11-01

    Full Text Available Background. The recent scale-up of antiretroviral therapy (ART coverage in resource-limited settings has greatly improved access to treatment. However, increasing numbers of patients are failing first- and second-line ART. Objective. To examine factors affecting adherence to second-line ART from the perspective of clinic staff and patients, assessing both individual and structural perceived barriers. Methods. Research was conducted at a large primary care tuberculosis (TB/HIV clinic in Khayelitsha, a peri-urban township in Cape Town, South Africa. Participants were drawn from a Médecins Sans Frontières-run programme to support patients failing second-line ART. A qualitative research approach was used, combining multiple methodologies including key informant interviews with staff (n=11, in-depth interviews with patients (n=10 and a Photovoice workshop (n=11. Responses and photographs were coded by content; data were transformed into variables and analysed accordingly. Results. Staff identified drinking, non-disclosure, not using condoms and pill fatigue as barriers to ART adherence, while patients identified side-effects, not using condoms and a lack of understanding concerning medication timing. With respect to service delivery, staff identified a need for continued counselling and educational support following ART initiation. Patients were concerned about missing medical records and poor staff attitudes in the clinic. Conclusion. These findings identify discrepancies between provider and patient perceptions of barriers to, and facilitators of adherence, as well as of service delivery solutions. This highlights the need for on-going counselling and education following ART initiation, improved quality of counselling, and improved methods to identify and address specific barriers concerning medication adherence.

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

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    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.

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

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    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.

  16. Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

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    Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

    2017-06-28

    Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

  17. Aflibercept as a second-line therapy in metastatic colorectal cancer: A limited Indian experience

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    Govind Babu

    2016-01-01

    Full Text Available Introduction: Aflibercept in combination with FOLFIRI has been shown to improve overall survival in the pivotal VELOUR study. Aflibercept has not yet been marketed in India. Sanofi has made available this drug for Indian patients under a program called Named Patient Access Program (NPP. We present a limited clinical experience with the use of aflibercept at our center. Materials and Methods: We analyzed the data of the patients who received aflibercept under NPP. Aflibercept was given in combination with FOLFIRI as second-line for patients who progressed on oxaliplatin based therapy. Aflibercept was given at 4 mg/kg intravenous (IV every 15 days. Chemotoxicities were assessed as per CTCAE. Response evaluation was done every four cycles. Results: Five patients were enrolled. The median age was 34 years. The median number of aflibercept cycles administered was 12. Common grade 2/3 toxicities were mucositis, diarrhea, neutropenia thrombocytopenia, and hypertension seen in three (60%, three (60%, two (40%, two (40%, and one patient respectively. After four cycles, the response was assessed as: One complete remission (CR, three partial remissions (PR, and one progressive disease (PD. Three patients completed 12 cycles of chemotherapy and aflibercept. At the end of 12 cycles, one patient still in CR and two patients were in PR. Four patients were alive till date. Conclusion: As we had very less number of patients, it was very difficult to compare it with VELOUR data. It is one of option as second-line in metastatic colorectal cancer (mCRC who progressed on oxaliplatin chemotherapy. Mucositis, diarrhea, and hematological toxicity were the most common toxicity in our patient.

  18. Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

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    Rottenfusser Andrea

    2009-10-01

    Full Text Available Abstract Background In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression. Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. Methods Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values Results Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26, and 8 months (95% CI 6.25-9.74 on first-line, respectively (n.s.. In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. Conclusion Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.

  19. Hemibody irradiation. An effective second-line therapy in drug-resistance multiple myeloma

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    Singer, C.R.; Tobias, J.S.; Giles, F.; Rudd, G.N.; Blackman, G.M.; Richards, J.D.

    1989-01-01

    The authors report the results of treatment of 41 patients with melphalan-resistant multiple myeloma using single half-body irradiation (HBI) or double half-body irradiation (DHBI). Patients were grouped using prognostic classification reported by the Medical Research Council. Patients in group I and II showed the best response to therapy with reduction in serum of urinary paraprotein and improvement in symptoms, most notably a marked reduction in bone pain. In these groups five patients have survived over 2 years after therapy. The therapeutic response appeared better in those patients who received DHBI as opposed to those whom treated with single HBI. Patients in group III did not achieve prolonged survival but effective relief of bone pain was a consistent finding in these patients also. Thus HBI represents an alternative to combination chemotherapy as second-line treatment of patients with melphalan-resistant multiple myeloma. A comparative study of HBI versus combination chemotherapy is now indicated to establish which therapeutic approach is most effective

  20. Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

    Science.gov (United States)

    Al Askar, Ahmed S; Shaheen, Naila A; Al Zahrani, Mohsen; Al Otaibi, Mohammed G; Al Qahtani, Bader S; Ahmed, Faris; Al Zughaibi, Mohand; Kamran, Ismat; Mendoza, May Anne; Khan, Altaf

    2018-01-01

    Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

  1. 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.

  2. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

  3. 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.

  4. Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

    Directory of Open Access Journals (Sweden)

    Matthew Arentz

    Full Text Available Use of antiretroviral therapy (ART during treatment of drug susceptible tuberculosis (TB improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR 3.4, 95% CI 1.6-7.4 and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6 during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3 and less than 50 cells/mm(3, and when correcting for drug resistance pattern.We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

  5. Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    De Velasco, Guillermo; Xie, Wanling; Donskov, Frede

    2017-01-01

    BACKGROUND: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason ...

  6. Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

    International Nuclear Information System (INIS)

    Karachaliou, Niki; Rosell, Rafael

    2014-01-01

    Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KRAS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of “hills” (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected

  7. 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...

  8. The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

    Science.gov (United States)

    Estill, Janne; Ford, Nathan; Salazar-Vizcaya, Luisa; Haas, Andreas D; Blaser, Nello; Habiyambere, Vincent; Keiser, Olivia

    2016-03-01

    The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line

  9. 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.

  10. [Influence of Saccharomyces boulardii Sachets combined with bismuth quadruple therapy for initial Helicobacter pylori eradication].

    Science.gov (United States)

    Zhu, X Y; Du, J; Wu, J; Zhao, L W; Meng, X; Liu, G F

    2017-08-08

    Objective: To evaluate the efficacy and safety of Saccharomyces boulardii Sachets combined with bismuth quadruple therapy for initial Helicobacter pylori ( H . pylori ) eradication. Methods: From March 2014 to March 2015, 240 participants from the third hospital of Hebei medical university with H . pylori infection were recruited and randomized into three groups: Quadruple therapy group received bismuth potassium citrate 220 mg bid + Rabeprazole 10 mg bid + amoxicillin 1 000 mg bid+ furazolidone 100 mg bid for 10 days. Short-term group and long-term group received the same quadruple therapy for 10 days as above, as well as Saccharomyces boulardii Sachets 500 mg bid for 14 days and 28 days, respectively. H . pylori eradication was confirmed by (13)C/(14)C-UBT at least 4 weeks after completion of therapy. And side effects were investigated during the therapy. Results: The H . pylori eradication rates in quadruple therapy, short-term and long-term group were 80%, 87.5% and 87.5% by ITT analysis ( P =0.321) and 92.8%, 94.6% and 95.9% by PP analysis ( P =0.717), respectively. The overall side effect rate and occurrence of diarrhea and abdominal distension were significantly lower in short-term or long-term group as compared with quadruple therapy group( P =0.007, 0.003, 0.004), but there was no significant difference between the two probiotics groups. Conclusions: Both short and long-term Saccharomyces boulardii Sachets reduced the overall side effect rate and occurrence of diarrhea or abdominal distension when combined with bismuth quadruple therapy for initial H . pylori eradication and no difference was observed in efficacy or safety between the two groups.

  11. Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments.

    Science.gov (United States)

    Gisbert, Javier P; Romano, Marco; Molina-Infante, Javier; Lucendo, Alfredo J; Medina, Enrique; Modolell, Inés; Rodríguez-Tellez, Manuel; Gomez, Blas; Barrio, Jesús; Perona, Monica; Ortuño, Juan; Ariño, Inés; Domínguez-Muñoz, Juan Enrique; Perez-Aisa, Ángeles; Bermejo, Fernando; Domínguez, Jose Luis; Almela, Pedro; Gomez-Camarero, Judith; Millastre, Judith; Martin-Noguerol, Elisa; Gravina, Antonietta G; Martorano, Marco; Miranda, Agnese; Federico, Alessandro; Fernandez-Bermejo, Miguel; Angueira, Teresa; Ferrer-Barcelo, Luis; Fernández, Nuria; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  12. Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type 2 Diabetes in China.

    Science.gov (United States)

    Gu, Shuyan; Zeng, Yuhang; Yu, Demin; Hu, Xiaoqian; Dong, Hengjin

    2016-01-01

    This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone. Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's perspective and estimated over a patient's lifetime. SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses. SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment.

  13. Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

    Science.gov (United States)

    Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

    2017-05-01

    Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

  14. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

    2015-01-01

    BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient...

  15. Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion.

    Science.gov (United States)

    Virgo, Katherine S; Basch, Ethan; Loblaw, D Andrew; Oliver, Thomas K; Rumble, R Bryan; Carducci, Michael A; Nordquist, Luke; Taplin, Mary-Ellen; Winquist, Eric; Singer, Eric A

    2017-06-10

    Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .

  16. Biweekly cetuximab and irinotecan as second-line therapy in patients with gastro-esophageal cancer previously treated with platinum

    DEFF Research Database (Denmark)

    Schoennemann, Katrine R; Bjerregaard, Jon K; Hansen, Tine P

    2011-01-01

    toxicities were: diarrhea (8%), fatigue (10%), neutropenia (16%), and febrile neutropenia (2%). CONCLUSION: Cetiri every two weeks is a convenient and well-tolerated second-line regimen in GEC patients. A promising effect was seen in patients with PS 0-1 and in patients who developed a rash....

  17. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Reck, Martin

    2017-01-01

    PATIENTS & METHODS: We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer. RESULTS: Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel...

  18. [Drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter pylori infection: a network Meta-analysis].

    Science.gov (United States)

    Gou, Q Y; Yu, R B; Shi, R H

    2017-05-10

    Objective: To compare the efficacy and the risk of adverse effect of drug susceptibility test guided therapy and novel empirical quadruple therapy for Helicobacter ( H .) pylori infection. Methods: Literature retrieval was conducted by using major databases. Related papers published up to June 2015 were considered eligible if they were randomized control trials comparing different pharmacological formulations for H. pylori infection and used in a network Meta-analysis and a single rate Meta-analysis to evaluate the relative and absolute rates of H. pylori eradication and the risk of adverse effect. The Jadad score was used to evaluate the methodological quality. Funnel plot was constructed to evaluate the risk of publication bias. Begg's rank correlation test or Egger's regression intercept test was done for the asymmetry of funnel plot. Results: Twenty randomized control trials for the treatment of 6 753 initial treated patients with H. pylori infection were included. Drug susceptibility test guided therapy was significantly superior to concomitant therapy, hybrid therapy, sequential therapy and bismuth quadruple therapy. The culture-based therapy had the highest likelihood of improving clinical efficacy, with lowest risk of adverse effect. Concomitant therapy had the highest probability of causing adverse effect despite its effectiveness. Hybrid therapy and bismuth quadruple therapy were associated with lower risk of adverse effect and higher effectiveness. Conclusion: Drug susceptibility test guided therapy showed superiority to other 4 interventions for H. pylori eradication mentioned above. Hybrid therapy and bismuth quadruple therapy might be applied in the settings where the culture-based strategy is not available.

  19. Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings

    DEFF Research Database (Denmark)

    Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo

    2014-01-01

    BACKGROUND: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations...... being identified. METHODS: An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa....... Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted...

  20. HIV drug resistance testing among patients failing second line antiretroviral therapy. Comparison of in-house and commercial sequencing.

    Science.gov (United States)

    Chimukangara, Benjamin; Varyani, Bhavini; Shamu, Tinei; Mutsvangwa, Junior; Manasa, Justen; White, Elizabeth; Chimbetete, Cleophas; Luethy, Ruedi; Katzenstein, David

    2017-05-01

    HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database. Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens. The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. 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...

  2. Randomized Phase II trial of paclitaxel plus valproic acid vs paclitaxel alone as second-line therapy for patients with advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Fushida S

    2015-04-01

    Full Text Available Sachio Fushida,1 Masahide Kaji,2 Katsunobu Oyama,1 Yasuo Hirono,3 Hideaki Nezuka,4 Toshiya Takeda,5 Tomoya Tsukada,1 Daisuke Fujimoto,3 Shigekazu Ohyama,6 Takashi Fujimura,7 Tetsuo Ohta1 On behalf of the Digestive Disease Support Organization (DDSO 1Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, 2Department of Surgery, Toyama Prefectural Central Hospital, Toyama, 3First Department of Surgery, Fukui University Hospital, Fukui, 4Department of Surgery, Yatsuo General Hospital, Toyama, 5Department of Surgery, Ishikawa Matto Central Hospital, Hakusan, 6Department of Surgery, Kanazawa Medical Center, Kanazawa, 7Toyama City Hospital, Toyama, Japan Abstract: The standard regimen of second-line chemotherapy for patients with unresectable gastric cancer has not been established. However, weekly paclitaxel (wPTX has become the preferable second-line chemotherapy in Japan. Histone deacetylase (HDAC inhibitors have been shown to have antiproliferative activity through cell-cycle arrest, differentiation, and apoptosis in gastric cancer cells. One HDAC inhibitor, valproic acid (VPA, also inhibits tumor growth by inducing apoptosis, and enhances the efficacy of paclitaxel in a mouse xenograft model of gastric cancer. wPTX plus VPA as a second-line chemotherapy is expected to improve survival in gastric cancer patients. A multicenter randomized Phase II study was conducted to compare the effects of wPTX plus VPA and wPTX alone. A total of 66 patients participated in this study. The primary end point of the study was overall survival, and secondary end points were progression-free survival, response rate, and assessment of peripheral neuropathy. Keywords: valproic acid, paclitaxel, second-line therapy, advanced gastric cancer 

  3. 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

  4. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  5. Economic analysis of the TAX 317 trial: docetaxel versus best supportive care as second-line therapy of advanced non-small-cell lung cancer.

    Science.gov (United States)

    Leighl, Natasha B; Shepherd, Frances A; Kwong, Rita; Burkes, Ronald L; Feld, Ronald; Goodwin, Pamela J

    2002-03-01

    To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non-small-cell lung cancer. A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada's public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. The incremental survival benefit in the docetaxel arm over BSC was 2 months (P =.047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m(2), the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of drugs, investigations, radiotherapy, and community care. BSC patients had fewer hospitalizations than patients in the chemotherapy arm and were more often palliated at home. Although the decision to treat should not be based on economic considerations alone, our CE estimate of $31,776 per year of life gained (at the currently recommended dose of docetaxel) is within an acceptable range of health care expenditures, and the total costs of therapy are similar to those of second-line palliative chemotherapy for other solid tumors.

  6. 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.

  7. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives.

    Science.gov (United States)

    Gurgle, Holly E; White, Karen; McAdam-Marx, Carrie

    2016-01-01

    Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM) who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient.

  8. 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.

  9. 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.

  10. 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.

  11. Busulfan is effective second-line therapy for older patients with Philadelphia-negative myeloproliferative neoplasms intolerant of or unresponsive to hydroxyurea.

    Science.gov (United States)

    Douglas, Genevieve; Harrison, Claire; Forsyth, Cecily; Bennett, Michael; Stevenson, William; Hounsell, John; Ratnasingam, Sumita; Ritchie, David; Ross, David M; Grigg, Andrew

    2017-01-01

    Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.

  12. Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

    DEFF Research Database (Denmark)

    Davis, Ian D; Xie, Wanling; Pezaro, Carmel

    2017-01-01

    BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type...... of therapy and change in IMDC prognostic category. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined......% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03). CONCLUSIONS: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy...

  13. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: A phase II Southwest Oncology Group Study (S0415)

    Science.gov (United States)

    Gold, Philip J.; Goldman, Bryan; Iqbal, Syma; Leichman, Lawrence P.; Zhang, Wu; Lenz, Heinz-Josef; Blanke, Charles D.

    2010-01-01

    Introduction Esophageal adenocarcinomas commonly express the Epidermal Growth Factor Receptor (EGFR). This trial assessed the six month overall survival probability in metastatic esophageal cancer patients treated with cetuximab as second line therapy. Methods This was a multicenter, open-label phase II study of single agent cetuximab for metastatic esophageal adenocarcinoma patients who failed one prior chemotherapy regimen. Adequate organ function and Zubrod performance status of 0-2 were required. Patients received cetuximab 400mg/m2 IV on week one, and 250 mg/m2 IV weekly thereafter. The primary objective was to determine 6 month overall survival. Secondary endpoints included progression-free survival, response rate, and toxicity. Tumor tissue was collected for correlative studies. Results Sixty-three patients were registered, with 8 ineligible or never treated. Fifty-five eligible patients (male=49, female=6; median age=61.2 years [range 30.7-88.5]) were enrolled. Twenty patients survived > 6 months for a 6-month overall survival rate of 36% (95% CI: 24%, 50%). The median overall survival was 4.0 months (95% CI: 3.2, 5.9). Median progression-free survival was 1.8 months (95% CI: 1.7, 1.9). One partial response and 2 unconfirmed partial responses were observed. Two patients experienced grade 4 fatigue. There was one treatment-related death due to pneumonitis. Germline polymorphisms of EGFR, EGF, IL-8, COX-2, VEGF, CCND1, NRP1 and Kras mutational status were not associated with response or survival. Conclusions The 6-month overall survival rate of 36% observed on this study failed to meet the primary survival objective. Thus, cetuximab alone cannot be recommended in the second-line treatment of metastatic esophageal cancer. PMID:20631636

  14. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Science.gov (United States)

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  15. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    Directory of Open Access Journals (Sweden)

    Chunxiang Zhang

    Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  16. 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.

    Science.gov (United States)

    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

    2012-06-01

    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 countries and predicted their impact on second-line drug susceptibility. A total of 2588 antiretroviral-naive individuals initiated ART consisting of different nucleoside reverse transcriptase inhibitor (NRTI) backbones (zidovudine, stavudine, tenofovir, or abacavir, plus lamivudine or emtricitabine) with either efavirenz or nevirapine. Population sequencing after 12 months of ART was retrospectively performed if HIV RNA was >1000 copies/mL. The 2010 International Antiviral Society-USA list was used to score major DRMs. The Stanford algorithm was used to predict drug susceptibility. HIV-1 sequences were generated for 142 participants who virologically failed ART, of whom 70% carried ≥1 DRM and 49% had dual-class resistance, with an average of 2.4 DRMs per sequence (range, 1-8). The most common DRMs were M184V (53.5%), K103N (28.9%), Y181C (15.5%), and G190A (14.1%). Thymidine analogue mutations were present in 8.5%. K65R was frequently selected by stavudine (15.0%) or tenofovir (27.7%). Among participants with ≥1 DRM, HIV-1 susceptibility was reduced in 93% for efavirenz/nevirapine, in 81% for lamivudine/emtricitabine, in 59% for etravirine/rilpivirine, in 27% for tenofovir, in 18% for stavudine, and in 10% for zidovudine. Early failure detection limited the accumulation of resistance. After stavudine failure in African populations, zidovudine rather than tenofovir may be preferred in second-line ART. Strategies to prevent HIV-1 resistance are a global priority.

  17. 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....

  18. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Gurgle HE

    2016-06-01

    Full Text Available Holly E Gurgle, Karen White, Carrie McAdam-Marx Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA Abstract: Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium–glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient. Keywords: type 2 diabetes mellitus, GLP-1 receptor agonist, SGLT2 inhibitor, A1c, weight loss, adverse effect

  19. Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer. A systematic review and meta-analysis of published studies.

    Science.gov (United States)

    Iacovelli, Roberto; Pietrantonio, Filippo; Farcomeni, Alessio; Maggi, Claudia; Palazzo, Antonella; Ricchini, Francesca; de Braud, Filippo; Di Bartolomeo, Maria

    2014-01-01

    Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79-0.85; posterior probability HR≥1: Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient's performance status. New trials based on a better patient stratification are awaited.

  20. Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer.

    Science.gov (United States)

    Sanoff, Hanna K; Goldberg, Richard M; Ivanova, Anastasia; O'Reilly, Seamus; Kasbari, Samer S; Kim, Richard D; McDermott, Ray; Moore, Dominic T; Zamboni, William; Grogan, William; Cohn, Allen Lee; Bekaii-Saab, Tanios S; Leonard, Gregory; Ryan, Theresa; Olowokure, Olugbenga O; Fernando, Nishan H; McCaffrey, John; El-Rayes, Bassel F; Horgan, Anne M; Sherrill, Gary Bradley; Yacoub, George Hosni; O'Neil, Bert H

    2018-06-15

    Regorafenib, a multikinase inhibitor that inhibits angiogenesis, growth, and proliferation, prolongs survival as monotherapy in patients with refractory colorectal cancer. This international, double-blind, placebo-controlled, multicenter trial assessed the efficacy of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer. Patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine enrolled at 45 sites in the United States and Ireland. Patients, stratified by prior bevacizumab use, were randomized 2:1 to regorafenib or placebo. The treatment consisted of FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle. Crossover was not allowed. The primary endpoint was progression-free survival (PFS). Under the assumption of a 75% event rate, 180 patients were required for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1. One hundred eighty-one patients were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI) with a median age of 62 years. Among these, 117 (65%) received prior bevacizumab or aflibercept. PFS was longer with regorafenib-FOLFIRI than placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P = .056). The median overall survival was not longer (HR, 1.01; 95% CI, 0.71-1.44). The response rate was higher with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) than placebo-FOLFIRI (21%; 95% CI, 11%-33%; P = .07). Grade 3/4 adverse events with a >5% absolute increase from regorafenib included diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension. The addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer only modestly prolonged PFS over FOLFIRI alone. Cancer 2018. © 2018 American Cancer

  1. Cost-effectiveness of saxagliptin vs glimepiride as a second-line therapy added to metformin in Type 2 diabetes in China.

    Science.gov (United States)

    Gu, Shuyan; Deng, Jing; Shi, Lizheng; Mu, Yiming; Dong, Hengjin

    2015-01-01

    This study aims to estimate the long-term cost-effectiveness of saxagliptin + metformin (SAXA + MET) vs glimepiride + metformin (GLI + MET) in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with MET in China. The Cardiff Model was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews and hospital surveys were conducted to obtain patients profiles, clinical data, and costs. Health insurance costs (2014¥) were estimated over a 40-year period. One-way and probabilistic sensitivity analyses were performed. SAXA + MET had lower predicted incidences of cardiovascular and hypoglycemia events and a decreased total cost compared with GLI + MET (¥241,072,807 vs ¥285,455,177). There were increased numbers of quality-adjusted life-years (QALYs; 1.01/patient) and life-years (Lys; 0.03/patient) gained with SAXA + MET compared with GLI + MET, and the incremental cost of SAXA + MET vs GLI + MET (-¥44,382) resulted in -¥43,883/QALY and -¥1,710,926/LY gained with SAXA + MET. Sensitivity analyses confirmed that the results were robust. In patients with T2DM in China, SAXA + MET was more cost-effective and was well tolerated with fewer adverse effects (AEs) compared with GLI + MET. As a second-line therapy for T2DM, SAXA may address some of the unmet medical needs attributable to AEs in the treatment of T2DM.

  2. Ten-day bismuth-containing quadruple therapy is effective as first-line therapy for Helicobacter pylori-related chronic gastritis: a prospective randomized study in China.

    Science.gov (United States)

    Wang, L; Lin, Z; Chen, S; Li, J; Chen, C; Huang, Z; Ye, B; Ding, J; Li, W; Wu, L; Jiang, Y; Meng, L; Du, Q; Si, J

    2017-06-01

    To investigate the effectiveness of 10-day bismuth-containing quadruple (B-quadruple) treatment as first-line therapy in patients with Helicobacter pylori-related chronic gastritis. A randomized controlled trial was conducted from October 2011 to December 2013 in Zhejiang, China, including patients with H. pylori-related chronic gastritis who were randomly provided either 10-day omeprazole-based triple therapy (OM-triple; omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily) or 10-day B-quadruple therapy (OM-triple + bismuth subcitrate 120 mg four times daily). H. pylori status, pathologic findings and dyspeptic symptoms were assessed at baseline and after 3 months. The primary outcome was H. pylori eradication rates by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary outcomes were the histologic and symptomatic benefits from H. pylori eradication. A total of 351 patients with H. pylori-related chronic gastritis were recruited. The eradication rates of the OM-triple and B-quadruple groups were 58.4% (108/185) and 86.1% (143/166) respectively according to ITT analysis (p gastritis and intestinal metaplasia did not regress in both groups (n=326). The reduction of dyspeptic symptoms score was significantly higher in the B-quadruple group than in the OM-triple group (0.59±0.057 vs. 0.39±0.046) (p gastritis in China. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Perceived adherence barriers among patients failing second-line ...

    African Journals Online (AJOL)

    Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa. W Barnett, G Patten, B Kerschberger, K Conradie, DB Garone, G van Cutsem, CJ Colvin ...

  4. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life worldwide observational study (EDGE)

    Science.gov (United States)

    Mathieu, C; Barnett, A H; Brath, H; Conget, I; de Castro, J J; Göke, R; Márquez Rodriguez, E; Nilsson, P M; Pagkalos, E; Penfornis, A; Schaper, NC; Wangnoo, S K; Kothny, W; Bader, G

    2013-01-01

    Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p vildagliptin and other OADs were consistent with previous data. Conclusion EDGE demonstrates that in a ‘real-life’ setting, vildagliptin as second OAD can lower HbA1c to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs. PMID:23961850

  5. Utility of MYD88 in the Differential Diagnosis and Choice of Second-Line Therapy in a Case of Nonsecretory Lymphoplasmacytic Lymphoma versus Free Light Chain Waldenstrom’s Macroglobulinemia

    Directory of Open Access Journals (Sweden)

    D. Kazmierski

    2017-01-01

    Full Text Available The MYD88 L265P somatic variant (MYD88 has a high prevalence in Waldenstrom’s Macroglobulinemia (WM, a form of lymphoplasmacytic lymphoma (LPL associated with monoclonal IgM. Although the role of MYD88 in WM was initially reported in 2012, it was not until 2016 that MYD88 testing was included in the National Cancer Care Network (NCCN Guidelines. We present a case illustrating the utility of MYD88 status in distinguishing atypical forms of WM from marginal zone lymphoma (MZL and in selecting second-line therapy with ibrutinib. In 2012, a 64-year-old male presented with dyspnea on exertion, a hemoglobin of 5.6 g/dL, a platelet count of 86,000, and monoclonal IgM kappa on serum immunofixation but no detectable M-spike. Bone marrow biopsy revealed 95% monoclonal B-lymphocytes with lymphoplasmacytic differentiation favoring a diagnosis of LPL/WM over MZL, with a favorable response to chemotherapy. This diagnosis was called into question 3 years later following relapse, and MZL was favored based on the lack of MYD88 mutation. One year later, however, repeat bone marrow biopsy detected the MYD88 mutation and therapy with ibrutinib yielded a favorable response. The distinction between certain lymphomas can be problematic and in this case MYD88 was helpful in clarifying a diagnosis of atypical LPL/WM from MZL and in selecting effective second-line therapy.

  6. Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study

    NARCIS (Netherlands)

    Nichols, Brooke E.; Sigaloff, Kim C. E.; Kityo, Cissy; Hamers, Raph L.; Baltussen, Rob; Bertagnolio, Silvia; Jordan, Michael R.; Hallett, Timothy B.; Boucher, Charles A. B.; de Wit, Tobias F. Rinke; van de Vijver, David A. M. C.

    2014-01-01

    Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. We develop a

  7. 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

  8. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

    Science.gov (United States)

    Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-08-02

    Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

  9. High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.

    Directory of Open Access Journals (Sweden)

    Cissy Kityo

    Full Text Available In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM versus routine laboratory (CD4/haematology/biochemistry and clinical monitoring (LCM in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317 participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717, abacavir (n = 300, or nevirapine (n = 300. Of 1896 (81.8% participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation, 1507 (79.5% were on first-line and 389 (20.5% on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (<50 cells/mm3. Among 1207 (80.1% first-line participants with viral load measured, HIV RNA was <400 copies/ml in 963 (79.8%, 400-999 copies/ml in 37 (3.1%, 1,000-9,999 copies/ml in 110 (9.1%, and ≥10,000 copies/ml in 97 (8.0%. The proportion with HIV RNA <400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5% in CDM (76.3% than in LCM (83.4%. Among 252 (64.8% second-line participants with viral load measured (median 2.3 years after switch, HIV RNA was <400 copies/ml in 226 (89.7%, with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.ISRCTN13968779.

  10. Applying the Quadruple Process model to evaluate change in implicit attitudinal responses during therapy for panic disorder.

    Science.gov (United States)

    Clerkin, Elise M; Fisher, Christopher R; Sherman, Jeffrey W; Teachman, Bethany A

    2014-01-01

    This study explored the automatic and controlled processes that may influence performance on an implicit measure across cognitive-behavioral group therapy for panic disorder. The Quadruple Process model was applied to error scores from an Implicit Association Test evaluating associations between the concepts Me (vs. Not Me) + Calm (vs. Panicked) to evaluate four distinct processes: Association Activation, Detection, Guessing, and Overcoming Bias. Parameter estimates were calculated in the panic group (n = 28) across each treatment session where the IAT was administered, and at matched times when the IAT was completed in the healthy control group (n = 31). Association Activation for Me + Calm became stronger over treatment for participants in the panic group, demonstrating that it is possible to change automatically activated associations in memory (vs. simply overriding those associations) in a clinical sample via therapy. As well, the Guessing bias toward the calm category increased over treatment for participants in the panic group. This research evaluates key tenets about the role of automatic processing in cognitive models of anxiety, and emphasizes the viability of changing the actual activation of automatic associations in the context of treatment, versus only changing a person's ability to use reflective processing to overcome biased automatic processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

    Science.gov (United States)

    Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

    2012-10-01

    This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

  12. Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan.

    Science.gov (United States)

    Miyake, Hideaki; Sugiyama, Takayuki; Aki, Ryota; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Otsuka, Atsushi

    2018-06-01

    The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC). The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60). The prostate-specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression-free survival (PFS), and overall survival (OS) during second-line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX; PSA PFS, AA-to-Enz vs. Enz-to-AA, AA-to-Enz vs. AA-to-DTX, Enz-to-AA vs. AA-to-DTX, and Enz-to-AA vs. Enz-to-DTX; and OS, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis. Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Clarithromycin vs. Gemifloxacin in Quadruple Therapy Regimens for Empiric Primary Treatment of Helicobacter pylori Infection: A Randomized Clinical Trial

    Science.gov (United States)

    Masoodi, Mohsen; Talebi-Taher, Mahshid; Tabatabaie, Khadijeh; Khaleghi, Siamak; Faghihi, Amir-Hossein; Agah, Shahram; Asadi, Reyhaneh

    2015-01-01

    BACKGROUND Eradication of Helicobacter pylori infection plays a crucial role in the treatment of peptic ulcer. Clarithromycin resistance is a major cause of treatment failure. This randomized clinical trial aimed at evaluating the efficacy of a clarithromycin versus gemifloxacin containing quadruple therapy regimen in eradication of H.pylori infection. METHODS In this randomized double blind clinical trial (RCT 2012102011054N2), a total of 120 patients were randomized to two groups of 60 patients each. Patients with proven H.pylori infection were consecutively assigned into two groups to receive OBAG or OBAC in gastroenterology clinic in Rasoul-e- Akram General Hospital in Tehran, Iran. The patients in the OBAG group received omeprazole (20 mg) twice daily, bismuth subcitrate (240 mg) twice daily, amoxicillin (1 gr) twice daily, and gemifloxacin (320 mg) once daily, and those in the OBAC group received omeprazole (20 mg) twice daily, 240 mg of bismuth subcitrate twice daily, amoxicillin (1 gr) twice daily, and clarithromycin (500 mg) twice daily for 10 days. RESULTS Five patients from each group were excluded from the study because of poor compliance, so 110 patients completed the study. The intention-to-treat eradication rate was 61.6% and 66.6% for the OBAC and OBAG groups, respectively. According to the per protocol analysis, the success rates of eradication of H.pylori infection were 67.2% and 72.7% for OBAC and OBAG groups, respectively (p=0.568). CONCLUSION The results of this study suggest that gemifloxacin containing regimen is at least as effective as clarithromycin regimen; hence, this new treatment could be considered as an alternative for the patients who cannot tolerate clarithromycin. PMID:26106468

  14. 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

  15. VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist.

    Science.gov (United States)

    Torrente-Segarra, Vicenç; Acosta Pereira, Asunción; Morla, Rosa; Ruiz, José Miguel; Clavaguera, Teresa; Figuls, Ramon; Corominas, Hector; Geli, Carme; Roselló, Rosa; de Agustín, Juan José; Alegre, Cayetano; Pérez, Carolina; García, Angel; Rodríguez de la Serna, Arturo

    to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

    Science.gov (United States)

    Gisbert, J P; Perez-Aisa, A; Rodrigo, L; Molina-Infante, J; Modolell, I; Bermejo, F; Castro-Fernández, M; Antón, R; Sacristán, B; Cosme, A; Barrio, J; Harb, Y; Gonzalez-Barcenas, M; Fernandez-Bermejo, M; Algaba, A; Marín, A C; McNicholl, A G

    2014-02-01

    Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

  17. Second Line of Defense Spares Program Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Dale L.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.

    2012-11-20

    The Office of the Second Line of Defense (SLD) is part of the Department of Energy‘s (DOE) National Nuclear Security Administration (NNSA). The SLD Program accomplishes its critical global security mission by forming cooperative relationships with partner countries to install passive radiation detection systems that augment traditional inspection and law enforcement measures by alerting border officials to the presence of special nuclear or other radiological materials in cross-border traffic. An important tenet of the program is to work collaboratively with these countries to establish the necessary processes, procedures, infrastructure and conditions that will enable them to fully assume the financial and technical responsibilities for operating the equipment. As the number of operational deployments grows, the SLD Program faces an increasingly complex logistics process to promote the timely and efficient supply of spare parts.

  18. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

    Science.gov (United States)

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-11-01

    Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17

  19. Second Line of Defense Spares Program

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.

    2012-11-20

    During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.

  20. 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.

  1. Bismuth-Based Quadruple Therapy with Bismuth Subcitrate, Metronidazole, Tetracycline and Omeprazole in the Eradication of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Raymond Lahaie

    2001-01-01

    Full Text Available BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates (89.5%. The present study looked at a shorter treatment period by adding omeprazole and by reducing the dose of tetracycline.

  2. Greater than 95% success with 14-day bismuth quadruple anti- Helicobacter pylori therapy: a pilot study in US Hispanics.

    Science.gov (United States)

    Salazar, Cesar O; Cardenas, Victor M; Reddy, Rita K; Dominguez, Delfina C; Snyder, Lindsey K; Graham, David Y

    2012-10-01

    A combination capsule of bismuth, metronidazole, and tetracycline plus omeprazole given as 10-day therapy has an overall effectiveness of 92-93% in per-protocol analysis (Grade B) with eradication of 86-91% of metronidazole-resistant Helicobacter pylori. This study aimed to explore whether extending the duration to 14 days would improve overall effectiveness per protocol to ≥95% (Grade A) in a population in which metronidazole resistance was anticipated to exist. A one-arm, open-label pilot study of H. pylori-infected, asymptomatic/mildly dyspeptic adults, Hispanic residents of El Paso, Texas, received a 14-day course of omeprazole, plus the combination capsule. We cultured and Gram-stained specimens obtained using a minimally invasive orogastric brush. Helicobacter pylori status was determined by (13)C-urea breath test at 4 or more weeks post-therapy. Forty-seven subjects (7 men and 40 women, average age 42 years) were entered. The per-protocol effectiveness was 97.1% (33/34) (95% mid-P CI: 86.3, 99.9); 100% of metronidazole-resistant strains were eradicated. Side effects were mild and self-limited but contributed to nonadherence. Therapy taken for failure (p forms in all specimens. This pilot study supports the concept that 14-day OBMT therapy is likely to be more efficacious for H. pylori eradication (Grade A, PP basis) than a 10-day course where metronidazole resistance is suspected. If confirmed, 14 days should be recommended in populations where metronidazole resistance is common. © 2012 Blackwell Publishing Ltd.

  3. Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients.

    Science.gov (United States)

    Pradat, Pierre; Durant, Jacques; Brochier, Corinne; Trabaud, Mary-Anne; Cottalorda-Dufayard, Jacqueline; Izopet, Jacques; Raffi, François; Lucht, Frédéric; Gagnieu, Marie-Claude; Gatey, Caroline; Jacomet, Christine; Vassallo, Matteo; Dellamonica, Pierre; Cotte, Laurent

    2016-11-01

    We assessed the virological efficacy of a 6 month maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy combining tenofovir disoproxil fumarate/emtricitabine with maraviroc/raltegravir. HIV-1-infected naive patients were enrolled in an open label, single-arm, Phase 2 trial. All patients received maraviroc 300 mg twice daily, raltegravir 400 mg twice daily and tenofovir/emtricitabine for 24 weeks. Patients with stable HIV-RNA HIV-RNA HIV-RNA was 4.3 log copies/mL. All patients had CCR5-tropic viruses by genotropism and phenotropism assays. All but one patient had an HIV-RNA < 50 copies/mL at W24 and entered the simplification phase. Virological success was maintained at W48 in 88% (90% CI 79%-97%) of patients. N155H mutation was detected at failure in one patient. No tropism switch was observed. Raltegravir and maraviroc plasma exposure were satisfactory in 92% and 79% of 41 samples from 21 patients. Five severe adverse events (SAEs) were observed up to W48; none was related to the study drugs. Four patients presented grade 3 AEs; none was related to the study. No grade 4 AE was observed. No patient died. Maraviroc/raltegravir maintenance therapy following a 6 month induction phase with maraviroc/raltegravir/tenofovir/emtricitabine was well tolerated and maintained virological efficacy in these carefully selected patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. 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...

  5. Vinorelbine as first-line or second-line therapy for advanced breast cancer: a Phase I-II trial by the Danish Breast Cancer Co-operative Group

    DEFF Research Database (Denmark)

    Langkjer, S.T.; Ejlertsen, B.; Mouridsen, H.

    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...

  6. Clinical and economic analysis of effectiveness of Nivolumab (Opdivo® use as second-line monotherapy in adult patients with advanced renal cell carcinoma after previous systemic therapy

    Directory of Open Access Journals (Sweden)

    M. Yu. Frolov

    2017-01-01

    Full Text Available Objecktive. To conduct a comparative pharmacoeconomic analysis of using nivolumab (Opdivo® as monotherapy in advanced renal cell carcinoma (RCC in adult patients 2-line therapy.Materials and methods. “Cost–effectiveness” was assessed using a Markov model for one patient with advanced RCC. “Cost–effectiveness” analysis, “cost–utility” analysis “budget impact” analysis were performed. Overall survival and QALYs were included into the model as the effectiveness criteria. All the direct costs were calculated from the Russian healthcare system perspective.Results. Treatment with nivolumab was associated with lower total direct costs, less frequent adverse events compared with the combination lenvatinib + everolimus. Total costs per patient were 2 451 712 rubles and 5232592 rubles for nivolumab and the combination lenvatinib + everolimus, respectively. The incremental “cost–effectiveness” ratio was 5 561760 rubles per life-months gained and 2339823 rubles per quality-adjusted life month. A sensitivity analysis confirmed the base case results. “Budget impact” analysis showed that the using of nivolumab allows to save budget costs and to treat additional 198 patients without spending healthcare resources.Conclusion. The results of the study showed that using nivolumab (Opdivo® as monotherapy in advanced RCC in adult patients as 2-line therapy is clinically effective and “cost–effective” method of treatment of adult patients with RCC in theRussian Federation. 

  7. 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.

  8. 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

  9. Integrated quadruple stress echocardiography.

    Science.gov (United States)

    Picano, Eugenio; Morrone, Doralisa; Scali, Maria C; Huqi, Alda; Coviello, Katia; Ciampi, Quirino

    2018-04-11

    Stress Echocardiography (SE) is an established diagnostic technique. For 40 years, the cornerstone of the technique has been the detection of regional wall motion abnormalities (RWMA), due to the underlying physiologically-relevant epicardial coronary artery stenosis. In the last decade, three new parameters (more objective than RWMA) have shown the potential to integrate and comple- ment RWMA: 1- B-lines, also known as ultrasound lung comets, as a marker of extra-vascular lung water, measured using lung ultrasound with the 4-site simplified scan symmetrically of the antero- lateral thorax on the third intercostal space, from mid-axillary to anterior axillary and mid- clavicular line; 2-left ventricular contractile reserve (LVCR), assessed as the peak stress/rest ratio of left ventricular force, also known as elastance (systolic arterial pressure by cuff sphygmomanome- ter/end-systolic volume from 2D echocardiography); 3- coronary flow velocity reserve (CFVR) on left anterior descending coronary artery, calculated as peak stress/rest ratio of diastolic peak flow velocity assessed using pulsed-wave Doppler. The 4 parameters (RWMA, B-lines, LVCR and CFVR) now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-SE. IQ-SE optimizes the versatility of SE to include in a one-stop shop the core "ABCD" (Asynergy+B-lines+Contractile reserve+Doppler flowmetry) protocol. It allows a synoptic assess- ment of parameters mirroring the epicardial artery stenosis (RWMA), interstitial lung water (B- lines), myocardial function (LVCR) and small coronary vessels (CFVR). Each variable has a clear clinical correlate, different and complementary to all others: RWMA identify an ischemic vs non- ischemic heart; B-lines a wet vs dry lung; LVCR a strong vs weak heart; CFVR a warm vs cold heart. IQ-SE is highly feasible, with minimal increase in the imaging and analysis time, and obvi- ous diagnostic and prognostic impact also beyond coronary artery

  10. Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

    Science.gov (United States)

    Ciaffi, Laura; Koulla-Shiro, Sinata; Sawadogo, Adrien Bruno; Ndour, Cheik Tidiane; Eymard-Duvernay, Sabrina; Mbouyap, Pretty Rosereine; Ayangma, Liliane; Zoungrana, Jacques; Gueye, Ndeye Fatou Ngom; Diallo, Mohamadou; Izard, Suzanne; Bado, Guillaume; Kane, Coumba Toure; Aghokeng, Avelin Fobang; Peeters, Martine; Girard, Pierre Marie; Le Moing, Vincent; Reynes, Jacques; Delaporte, Eric

    2017-09-01

    Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI

  11. Title of the paper goes here second line

    Indian Academy of Sciences (India)

    %%Please download if these packages are not included %%in your local TeX distribution %%txfonts,balance,textcase,float %% \\begin{document} %%paper title %%For line breaks, \\\\ can be used within title \\title{Title of the paper goes here\\\\ second line} %%author names are separated by comma (,) %%use \\and before ...

  12. Title of the paper goes here second line

    Indian Academy of Sciences (India)

    Title of the paper goes here second line. AUTHOR11, AUTHOR21 and AUTHOR32,*. 1 Department of P, University X. 2 Department of Q, University Z. Abstract. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes ...

  13. Perceived adherence barriers among patients failing second-line ...

    African Journals Online (AJOL)

    1 School of Public Health and Family Medicine, University of Cape Town, South Africa ... To examine factors affecting adherence to second-line ART from the perspective of clinic staff and .... because she did not realise her VL would go up.

  14. 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 ...

  15. 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

  16. Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Anna Minchom

    2010-01-01

    Full Text Available Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7% achieved disease control. Median duration of response was 11 months (95% CI: 9–13. On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1% patients who failed to respond to first-line therapy achieved disease control. Eight (2.1% patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months. On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

  17. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

    Science.gov (United States)

    McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

    2018-03-08

    Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology

  18. Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

    Science.gov (United States)

    Lam, Simon W; Wai, Maya; Lau, Jessica E; McNamara, Michael; Earl, Marc; Udeh, Belinda

    2017-01-01

    Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified

  19. The efficacy of two-week quadruple first-line therapy with bismuth, lansoprazole, amoxicillin, clarithromycin on Helicobacter pylori eradication: a prospective study.

    Science.gov (United States)

    Ergül, Bilal; Doğan, Zeynal; Sarikaya, Murat; Filik, Levent

    2013-12-01

    To document the efficacy and tolerability of 14-day bismuth-lansoprazole-amoxicillin-clarithromycin (BLAC) regimen for Helicobacter pylori (H. pylori) eradication as a first-line therapy. Patients were considered eligible for the study if they underwent upper gastrointestinal endoscopy, and H. pylori infection was diagnosed through histologic examination of antral and body biopsy samples. Primary end point of this study was to evaluate the eradication rate of 14-day BLAC regimen therapies. H. pylori eradication was assessed using the 13C urea breath test performed 6 weeks after the completion of treatment. All patients were asked to fill in a validated questionnaire to report therapy-related side effects. Each symptom was graded from absent or present. Ninety-seven (21 men and 76 women) were enrolled. All the patients completed the study. The H. pylori eradication rate was 90.7% (88 of 97 patients). Side effects were observed in reasonable percentages, and none of the patients left the study because of drug side effect. Bismuth-lansoprazole-amoxicillin-clarithromycin regimen as a 2-week course achieved an acceptable eradication rate with relatively mild side effects. © 2013 John Wiley & Sons Ltd.

  20. Rescue Therapy for Helicobacter pylori Infection 2012

    Directory of Open Access Journals (Sweden)

    Javier P. Gisbert

    2012-01-01

    Full Text Available Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After 30 years of experience in H. pylori treatment, however, the ideal regimen to treat this infection has still to be found. Nowadays, apart from having to know well first-line eradication regimens, we must also be prepared to face treatment failures. In designing a treatment strategy, we should not only focus on the results of primary therapy alone but also on the final—overall—eradication rate. The choice of a “rescue” treatment depends on which treatment is used initially. If a first-line clarithromycin-based regimen was used, a second-line metronidazole-based treatment (quadruple therapy may be used afterwards, and then a levofloxacin-based combination would be a third-line “rescue” option. Alternatively, it has recently been suggested that levofloxacin-based “rescue” therapy constitutes an encouraging 2nd-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, quadruple regimen may be reserved as a 3rd-line “rescue” option. Even after two consecutive failures, several studies have demonstrated that H. pylori eradication can finally be achieved in almost all patients if several “rescue” therapies are consecutively given.

  1. 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.

  2. Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.

    Science.gov (United States)

    Boyd, Mark A; Amin, Janaki; Mallon, Patrick W G; Kumarasamy, Nagalingeswaran; Lombaard, Johan; Wood, Robin; Chetchotisakd, Ploenchan; Phanuphak, Praphan; Mohapi, Lerato; Azwa, Iskandar; Belloso, Waldo H; Molina, Jean-Michel; Hoy, Jennifer; Moore, Cecilia L; Emery, Sean; Cooper, David A

    2017-01-01

    Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N

  3. 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

  4. 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

  5. Second-line afatinib administration in an elderly patient with squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hohenforst-Schmidt W

    2017-03-01

    Full Text Available Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2 Michael Steinheimer,1 Naim Benhassen,3 Chrysanthi Sardeli,4 Nikos Stalikas,2 Melpomeni Toitou,2 Haidong Huang5 1Sana Clinic Group Franken, Department of Cardiology/Pulmonology/Intensive Care/Nephrology, “Hof” Clinics, University of Erlangen, Hof, Germany; 2Pulmonary Department – Oncology Unit, “G Papanikolaou” General Hospital, Thessaloniki, Greece; 3Medical Clinic I, “Fuerth” Hospital, University of Erlangen, Fuerth, Germany; 4Department of Pharmacology & Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Department of Respiratory and Critical Care Medicine, Changhai Hospital/First Affiliated Hospital of the Secondary Military Medical University, Shanghai, China Introduction: The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. Case report: This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg after disease progression with left lung atelectasis. After receiving afatinib for only 28 days, the atelectasis resolved. No adverse effects were observed from the afatinib therapy. Discussion: In this case, afatinib 40 mg proved to be an effective alternative treatment for an elderly patient. Treatment choice should be based on the performance status of the patient, cost-effectiveness, and drug treatment guidelines. Keywords: lung cancer, EGFR, afatinib

  6. 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...

  7. 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.

  8. 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

  9. A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Kim, Young Saing; Lee, Soon Il; Park, Se Hoon; Park, Silvia; Hwang, In Gyu; Lee, Sang-Cheol; Sun, Jong-Mu; Lee, Jeeyun; Lim, Ho Yeong

    2016-02-01

    The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic urothelial carcinoma. Weekly docetaxel was well tolerated but demonstrated modest activity, with a response rate of 6%, a median progression-free survival (PFS) of 1.4 months, and a median overall survival (OS) of 8.3 months. The dichotomy between PFS and OS was likely associated with subsequent platinum-based chemotherapy received by 58% of the patients. Docetaxel is commonly used for second-line therapy for metastatic urothelial carcinoma (UC). However, myelosuppression is a substantial concern when the traditional 3-week docetaxel cycle is used. The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic UC. Patients with progression after previous platinum-based chemotherapy for advanced or metastatic disease were treated with docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. The primary endpoint was the response rate. The study enrolled 31 patients. Their median age was 64 years (range, 40-79 years). An Eastern Cooperative Oncology Group performance status of 1, liver metastasis, and a hemoglobin level chemotherapy had been administered for metastatic disease in 29 patients (94%). Although fatigue (13%) and anorexia (6%) were the most frequently observed grade 3 to 4 toxicities, the safety profiles were generally mild and manageable. Two patients (6%) achieved an objective response, which was maintained for 3.0 to 7.8 months. Eight patients experienced disease stabilization (disease control rate, 32%). The median progression-free survival (PFS) and overall survival (OS) were 1.4 months (95% confidence interval [CI], 1.3-1.6) and 8.3 months (95% CI, 5.9-10.6), respectively. A relatively long OS was associated with further salvage platinum-based chemotherapy (n = 18, 58%) showing an encouraging activity (response rate, 44%; median PFS, 4.0 months

  10. Survival predictors for second-line chemotherapy in Caucasian patients with metastatic gastric cancer

    OpenAIRE

    Bohanes, Pierre; Courvoisier, Delphine; Perneger, Thomas; Morel, Philippe; Huber, Olivier; Roth, Arnaud

    2011-01-01

    There are very limited data suggesting a benefit for second-line chemotherapy in advanced gastric cancer. Therefore, the number of patients who receive further treatment after failure of first-line chemotherapy varies considerably, ranging from 14% to 75%. In the absence of a demonstrated survival benefit of second-line chemotherapy, appropriate selection of patients based on survival predictors is essential. However, no clinico-pathologic parameters are currently widely adopted in clinical p...

  11. 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.

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

    Science.gov (United States)

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

    2017-06-01

    In Vietnam, a country with high tuberculosis (137/100.000 population) and multidrug-resistant (MDR)-TB burdens (7.8/100.000 population), little is known about the molecular signatures of drug resistance in general and more particularly of second line drug (SLD) resistance. This study is specifically focused on Mycobacterium tuberculosis isolates resistant to four first-line drugs (FLDs) that make TB much more difficult to treat. The aim is to determine the proportion of SLD resistance in these quadruple drug resistant isolates and the genetic determinants linked to drug resistance to better understand the genetic processes leading to quadruple and extremely drug resistance (XDR). 91 quadruple (rifampicin, isoniazid, ethambutol and streptomycin) FLD resistant and 55 susceptible isolates were included. Spoligotyping and 24-locus MIRU-VNTR techniques were performed and 9 genes and promoters linked to FLD and SLD resistance were sequenced. SLD susceptibility testing was carried out on a subsample of isolates. High proportion of quadruple-FLD resistant isolates was resistant to fluoroquinolones (27%) and second-line injectable drugs (30.2%) by drug susceptibility testing. The sequencing revealed high mutation diversity with prevailing mutations at positions katG315, inhA-15, rpoB531, embB306, rrs1401, rpsL43 and gyrA94. The sensitivity and specificity were high for most drug resistances (>86%), but the sensitivity was lower for injectable drug resistances (resistance. Nevertheless, particular mutation patterns linked to high-level resistance and low fitness costs seem to be favored. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. 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.

  14. PREDICTORS OF OVERALL SURVIVAL IN PATIENTS WITH RECURRENT NON-SEMINOMATOUS GERMINAL TESTICULAR TUMORS ON CURRENT SECOND-LINE CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2010-01-01

    Full Text Available Objective: to define predictors that influence longevity in patients with recurrent non-seminomatous germinal testicular tumors (NGTT on standard second-line chemotherapy (CT including cisplatin and iphosphamide. Statistical analysis was performed using the statistical packages Graph Pad Prism 4.00 for Windows and SPSS 15.0 for Windows. Subjects and methods. Case history data were analyzed in 693 patients with disseminated NGTT who had received current CT and followed up at the Department of Clinical Pharmacology and CT, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. The median follow-up was 32 (range 3-215 months. The disease progressed in 181 (26% patients. Detailed information was available on the nature of second-line CT in only 138 patients. Half (71 (51.7% of the 138 patients had second-line CT including iphosphamide. Uni- and multivariate analyses were made to identify predictors that influence longevity in patients with recurrent NGTT on standard secondline CT including cisplatin and iphosphamide. Results. Five-year overall survival (OS was 32% (95% confidence interval 25-41%. The multivariate analysis showed the morphological pattern of a primary tumor (a yolk sac tumor component, a pre-induction CT lactate dehydrogenase (LDH level of ?d1.5 units of the upper normal range, progression during induction CT, and a pre-second-line CT LDH level of ?d 1000 U/l to be negative predictors. According to the number of negative factors, the patients were classified into 3 groups: 1 good prognosis [n = 10 (14% of the 71 patients], 100% 3-year OS; 2 intermediate prognosis (one negative factor [n = 33 (46.5% of the 71 patients], 50.2% 3-year OS; 3 poor prognosis (?d 2 negative factors, 6.7% 3-year OS. Conclusion. Standard iphosphamide-containing therapy enables all patients to be treated in the good prognosis group of those with recurrent NGTT. That fails to achieve such striking results in the intermediate and

  15. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Rothschild SI

    2014-09-01

    Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

  16. Second Line of Defense Virtual Private Network Guidance for Deployed and New CAS Systems

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Surya V.; Thronas, Aaron I.

    2010-01-01

    This paper discusses the importance of remote access via virtual private network (VPN) for the Second Line of Defense (SLD) Central Alarm System (CAS) sites, the requirements for maintaining secure channels while using VPN and implementation requirements for current and future sites.

  17. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes

    NARCIS (Netherlands)

    Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B.; Sotgiu, Giovanni; Cox, Helen S.; Holtz, Timothy H.; Hollm-Delgado, Maria-Graciela; Keshavjee, Salmaan; Deriemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G.; Bauer, Melissa; Menzies, Dick; Ahuja, S. D.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M. C.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E. D.; Chiang, C. Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W. C. M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K. L.; Flood, J.; Gandhi, N.; Garcia-Garcia, M. L.; Granich, R. M.; Hollm-Delgado, M. G.; Holtz, T. H.; Hopewell, P.; Iseman, M. D.; Jarlsberg, L. G.; Keshavjee, S.; Kim, H. R.; Koh, W. J.; Lancaster, J. L.; Lange, C.; Leimane, V.; Leung, C. C.; Li, J.

    2013-01-01

    A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable

  18. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Fadi Kayali

    2011-02-01

    Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

  19. Who will bear the torch tomorrow? Charismatic leadership and second-line leaders in development NGOs

    OpenAIRE

    M. Shameem Siddiqi

    2001-01-01

    Competent leadership has always been considered vital in every organisation and there has been considerable research on mainstream leadership issues in the corporate sector and in politics.1 But there has been very little research on leadership issues in the emerging sector of development NGOs. The issue of second-line leadership development2 is an important one not only for the NGOs themselves but also for the aid industry, the poor and vulnerable people for whom they work and for society as...

  20. Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

    International Nuclear Information System (INIS)

    Thompson, Scott M.; Callstrom, Matthew R.; McKusick, Michael A.; Woodrum, David A.

    2015-01-01

    PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA

  1. Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Scott M., E-mail: Thompson.scott@mayo.edu [Mayo Clinic, Mayo Graduate School, Mayo Medical School and the Mayo Clinic Medical Scientist Training Program, College of Medicine (United States); Callstrom, Matthew R., E-mail: callstrom.matthew@mayo.edu; McKusick, Michael A., E-mail: mckusick.michael@mayo.edu; Woodrum, David A., E-mail: woodrum.david@mayo.edu [Mayo Clinic, Department of Radiology, College of Medicine (United States)

    2015-10-15

    PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA.

  2. TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study.

    Science.gov (United States)

    Kabore, Firmin Nongodo; Eymard-Duvernay, Sabrina; Zoungrana, Jacques; Badiou, Stéphanie; Bado, Guillaume; Héma, Arsène; Diouf, Assane; Delaporte, Eric; Koulla-Shiro, Sinata; Ciaffi, Laura; Cournil, Amandine

    2017-01-01

    Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33-46 years) and median T-CD4 count was 199 cells/μl (IQR: 113-319 cells/μl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36-72 months) and the median baseline SI was 101 (IQR: 87-116). In multivariable analysis, factors associated with baseline SI were sex (β = -10.8 [-18.1,-3.5] for women), age (β = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (β = +0.8 [0.1,1.5] per unit of BMI), and study site (β = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.

  3. 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.

  4. 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...

  5. 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

  6. "To look at death another way": Black teenage males' perspectives on second-lines and regular funerals in New Orleans.

    Science.gov (United States)

    Bordere, Tashel C

    The purpose of this study was to describe how Black adolescent males understand "second-line" (musical processions) and "regular"/traditional funeral rituals in New Orleans following the violent deaths of significant persons in their lives. In-depth interviews were conducted with 10 Black males between the ages of 12 and 15 using descriptive phenomenology methodology. Findings revealed that these participants understood death as a cause for celebration, remembrance, and unity related to their experiences with the second-line ritual. Three elements of the life world of Black teenage males were descriptive of second lines, including: a) observed locations of second lines; b) dancing to good music; and c) observed messages conveyed through t-shirts. Participants provided gender-based descriptions of perceived spoken and unspoken rights in grieving at the two distinct rituals. Related to their second-line experience, the teens reflect on ways in which they wish to have their deaths ritualized.

  7. 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...

  8. Quadruple suspension design for Advanced LIGO

    International Nuclear Information System (INIS)

    Robertson, N A; Cagnoli, G; Crooks, D R M; Elliffe, E; Faller, J E; Fritschel, P; Gossler, S; Grant, A; Heptonstall, A; Hough, J; Lueck, H; Mittleman, R; Perreur-Lloyd, M; Plissi, M V; Rowan, S; Shoemaker, D H; Sneddon, P H; Strain, K A; Torrie, C I; Ward, H; Willems, P

    2002-01-01

    In this paper, we describe the conceptual design for the suspension system for the test masses for Advanced LIGO, the planned upgrade to LIGO, the US laser interferometric gravitational-wave observatory. The design is based on the triple pendulum design developed for GEO 600 - the German/UK interferometric gravitational wave detector. The GEO design incorporates fused silica fibres of circular cross-section attached to the fused silica mirror (test mass) in the lowest pendulum stage, in order to minimize the thermal noise from the pendulum modes. The damping of the low-frequency modes of the triple pendulum is achieved by using co-located sensors and actuators at the highest mass of the triple pendulum. Another feature of the design is that global control forces acting on the mirrors, used to maintain the output of the interferometer on a dark fringe, are applied via a triple reaction pendulum, so that these forces can be implemented via a seismically isolated platform. These techniques have been extended to meet the more stringent noise levels planned for in Advanced LIGO. In particular, the Advanced LIGO baseline design requires a quadruple pendulum with a final stage consisting of a 40 kg sapphire mirror, suspended on fused silica ribbons or fibres. The design is chosen to aim to reach a target noise contribution from the suspension corresponding to a displacement sensitivity of 10 -19 m Hz -1/2 at 10 Hz at each of the test masses

  9. 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

  10. 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.

  11. Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Hyejin Kim

    2013-01-01

    Full Text Available Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required.

  12. SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Deyan N. Davidov

    2013-04-01

    Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

  13. Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

    Science.gov (United States)

    Kiraz, S; Baltali, E; Güler, N; Barista, I; Benekli, M; Celik, I; Güllü, I H; Kars, A; Tekuzman, G; Firat, D

    1996-08-01

    The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

  14. Second Line of Defense Megaports Initiative Operational Testing and Evaluation Plan Colon Container Terminal (CCT) Panama

    Energy Technology Data Exchange (ETDEWEB)

    Newhouse, Robert N.

    2010-01-01

    Report on the Operational Testing and Evaluation to validate and baseline an operable system that meets the Second Line of Defense (SLD) mission requirements. An SLD system is defined as the detection technology and associated equipment, the system operators from the host country, the standard operating procedures (SOPs), and other elements such as training and maintenance which support long-term system sustainment. To this end, the activities conducted during the OT&E phase must demonstrate that the Megaports System can be operated effectively in real-time by Panama Direccion General de Aduanas (DGA Panama Customs) personnel to the standards of the U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA).

  15. 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

  16. Experience with second line drugs in frequently relapsing and steroid dependent childhood nephrotic syndrome in a large Saudi center

    Directory of Open Access Journals (Sweden)

    Khalid Alsaran, M.D.

    2017-06-01

    Conclusion: All the second line drugs in our study were equally effective. However, we recommend that the initial treatment of FR/SD nephrotic syndrome should be chosen with the least toxic yet equally efficacious drug Levamisole.

  17. 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.

  18. 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.

  19. Second-line chemotherapy with dacarbazine and fotemustine in nitrosourea-pretreated patients with recurrent glioblastoma multiforme.

    Science.gov (United States)

    Fazeny-Dörner, Barbara; Veitl, Mario; Wenzel, Catharina; Piribauer, Maria; Rössler, Karl; Dieckmann, Karin; Ungersböck, Karl; Marosi, Christine

    2003-07-01

    The aim of this study was to assess the efficacy and toxicity of a combination of dacarbazine (D) and fotemustine (F) administered to a homogenous group of patients with recurrent or progressive glioblastoma multiforme (GBM). Thirty-one patients with computed tomography or magnetic resonance imaging scan evidence of recurrent or progressive GBM after first-line chemotherapy with nitrosoureas as well as radiation therapy were given a combination of D (200 mg/m2) and F (100 mg/m2). At 30 min after termination of D administration, F was given over 60 min. Treatment was performed in an outpatient setting every 21 days. A total of 140 cycles (range 1-12 cycles; median 4 cycles) was administered. One partial response (3%) lasting for 11 weeks was observed. Sixteen (52%) patients reached stable disease lasting between 7 and 94 weeks. Median survival from start of the D/F combination was 45 (range 10-150) weeks. Median time to progression was 17 (3-101) weeks for all patients. Major toxicity was myelosuppression resulting in exclusion from study in seven (23%) patients [due to thrombocytopenia common toxicity criteria (CTC) grade 2 persisting longer than 3 weeks in three patients, due to thrombocytopenia CTC grade >/=3 in three and due to leukopenia CTC grade 3 in one patient]. No other toxicity than alopecia occurred. We conclude that the D/F combination is a well-tolerated second-line regimen and can be administered in a complete outpatient setting. D/F shows efficacy even in nitrosourea-pretreated patients and justifies further investigation.

  20. A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

    Science.gov (United States)

    Ongubo, Dennis Miyoge; Lim, Robertino; Tweya, Hannock; Stanley, Christopher Chikhosi; Tembo, Petros; Broadhurst, Richard; Gugsa, Salem; Ngongondo, McNeil; Speight, Colin; Heller, Tom; Phiri, Sam; Hosseinipour, Mina C

    2017-07-03

    Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p bilirubin levels (aOR 5.4, p bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

  1. Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

    Science.gov (United States)

    Laing, R O; McGoldrick, K M

    2000-12-01

    Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

  2. Modeling and Simulation of a Modified Quadruple Tank System

    DEFF Research Database (Denmark)

    Mohd. Azam, Sazuan Nazrah; Jørgensen, John Bagterp

    2015-01-01

    to model and control. In this paper, a modified quadruple-tank system has been described, all the important variables has been outlined and a mathematical model has been presented. We developed deterministic and stochastic models using differential equations and simulate the models using Matlab...

  3. On the use of dental ceramics as a possible second-line approach to accident irradiation dosimetry

    International Nuclear Information System (INIS)

    Davies, J.E.

    1979-01-01

    Recent development in dental ceramic production has resulted in natural or depleted uranium, used for over half a century to mimic the fluorescence of natural teeth, being substituted in such ceramics by non-radioactive fluorescent materials. This creates the possibility of using dental ceramics incorporating the latter as second-line dosimeters in cases of accidental irradiation. This pilot study shows the feasbility of such an approach using both thermally stimulated exoelectron and thermoluminescent techniques. In conclusion, it is considered that it would be of interest to continue this investigation of dental ceramic materials as second-line accident dosimeters

  4. RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis.

    Science.gov (United States)

    Yang, Lin; Alyasova, Anna; Ye, Dingwei; Ridolfi, Antonia; Dezzani, Luca; Motzer, Robert J

    2018-02-17

    RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients. RECORD-4 enrolled patients with clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Patients received everolimus 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was progression-free survival per investigator review. Data cutoff was Sept 1, 2014. Among Asian (n = 55) versus non-Asian (n = 79) patients, 98% versus 84% had good/intermediate MSKCC prognosis; 73% versus 65% were men, and 85% versus 73% were < 65 years of age. All (100%) Asian patients were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian patients. Among Asian versus non-Asian patients, median progression-free survival (months) was 7.4 versus 7.8 overall, 7.4 versus 4.0 with prior sunitinib, and 5.7 versus 9.2 with prior other anti-VEGFs. Clinical benefit rate was similar between populations: 74.5% (95% CI 61.0-85.3) for Asian patients and 74.7% (95% CI 63.6-83.8) for non-Asian patients. Most patients achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events appeared similar for Asian (58%) and non-Asian patients (54%). This RECORD-4 subanalysis demonstrated comparable efficacy and adverse event profiles of second-line everolimus in Asian and non-Asian patients. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small

  5. 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

  6. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers.

    Science.gov (United States)

    Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong

    2015-08-01

    Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for

  7. U.S. second line of defense: preventing nuclear smuggling across Russia's borders

    International Nuclear Information System (INIS)

    Ball, D. Y.

    1998-01-01

    Preventing the theft of weapons-usable highly enriched uranium and plutonium in Russia is one of the central security concerns facing the US today. The dissolution of the highly centralized USSR and the resulting societal crisis has endangered Russia's ability to protect its more than 200 metric tons of plutonium and 1000 tons of highly enriched uranium (roughly 8 kg Pu or 25 kg HEU is sufficient to make a bomb). Producing this fissile material is the most difficult and expensive part of nuclear weapons production and the US must make every effort to ensure that fissile material (and nuclear-related technologies) does not reach the hands of terrorist groups, rogue states or other potential proliferators. In response to this concern, the US has undertaken a number of initiatives in partnership with Russia and other FSU states to prevent the theft of fissile material. The Material Protection, Control and Accounting Program (MPC and A) was begun in 1993 to prevent the theft of nuclear materials from Russian civilian complexes, that is facilities not under control of the Ministry of Defense, which is largely responsible for possession and oversight of nuclear weapons. The MPC and A program is considered the first line of defense against theft of nuclear material because its goal is to prevent theft of material at production and storage facilities. This year the Department of Energy (DOE) initiated a new program called the Second Line of Defense (SLD), the goal of which is to assist Russia in preventing the smuggling of nuclear material and weapons at its borders, either by land, sea or air. The SLD program represents an important phase in the overall effort to ensure the security of nuclear material and weapons in Russia. However, as the US engages Russian customs officials in this important project, Americans should keep in mind that providing equipment--even indigenous equipment--is insufficient by itself; material aid must be accompanied by rigorous inspection and

  8. Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting

    NARCIS (Netherlands)

    van Zyl, Gert Uves; van Mens, Thijs E.; McIlleron, Helen; Zeier, Michele; Nachega, Jean B.; Decloedt, Eric; Malavazzi, Carolina; Smith, Peter; Huang, Yong; van der Merwe, Lize; Gandhi, Monica; Maartens, Gary

    2011-01-01

    In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure. We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public

  9. Helicobacter pylori eradication therapy: A review of current trends.

    Science.gov (United States)

    Olokoba, A B; Obateru, O A; Bojuwoye, M O

    2013-01-01

    Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

  10. Where to Turn for Second-Line Cytoreduction After Hydroxyurea in Polycythemia Vera?

    Science.gov (United States)

    Nazha, Aziz; Gerds, Aaron T

    2016-04-01

    The goals of therapy in patients with polycythemia vera (PV) are to improve disease-related symptoms, prevent the incidence or recurrence of thrombosis, and possibly delay or prevent the transformation into myelofibrosis or acute myeloid leukemia (AML). Cytoreductive therapies have been used in older patients and those with a history of thrombosis to achieve these goals. Hydroxyurea (HU) remains the first-line cytoreductive choice; however, up to one in four patients treated with HU over time will develop resistance or intolerance to HU. More importantly, patients who fail HU have a 5.6-fold increase in mortality and a 6.8-fold increase risk of transformation to myelofibrosis or AML; therefore, alternative therapies are needed for these patients. Interferon-α has been used in PV and has shown significant activity in achieving hematologic responses and decreasing JAK2 V617F mutation allele burden. JAK inhibition has also been investigated and recently garnered regulatory approval for this indication. In this review, we will discuss the current treatment options that are available for patients after HU and the novel therapies that are currently under investigation. The outcomes of PV patients who fail or who are intolerant of hydroxyurea are poor. Although pegylated interferon can be considered in younger patients, currently, ruxolitinib is the only U.S. Food and Drug Administration-approved agent in this setting, representing a viable option, leading to hematocrit control and a reduction in spleen size and constitutional symptoms. Although a small number of patients will achieve a molecular response with continuous treatment, the implications of such response on the clinical outcomes are still unknown. Patients whose disease is not adequately controlled with ruxolitinib, or who lose their response, can be treated with low-dose busulfan or pipobroman; however, they should be encouraged to participate in trials with novel therapies. ©AlphaMed Press.

  11. Second line of defense program overview LA-UR-00-5161

    International Nuclear Information System (INIS)

    Knepper, P.L.; Martin, D.D.W.

    2001-01-01

    Full text: The illicit trafficking of nuclear material is a major concern for non-proliferation and global stability. The nuclear Material Protection, Control and Accounting (MPC and A) program provides the first line of defense in protecting nuclear materials within Russia by upgrading safeguards and security measures at Russian nuclear facilities. Second Line of Defense (SLD) is a cooperative program between the Russian Federation State Customs Committee (RF SCC) and the United States Department of Energy (US DOE) to minimize illicit trafficking of restricted nuclear materials through Russian border control points. This partnership was solidified with the signing of a protocol between DOE and the RF SCC in June 1998. The relationship will soon be formalized in a Memorandum of Understanding that will outline the working relationships and commitments to successful implementation of the SLD Program. The Russians first acknowledged the threat of nuclear smuggling at a Nuclear Safety Summit in Moscow in April 1996. Nikolai Kravehenko, head of the Regional Information and Technical Customs Department of the RF SCC, subsequently stated in a July 1998 interview, 'In order to stop trafficking and illegal shipment to other countries we [also] have to tighten security at the facilities and equip our borders with reliable technology.' At the September 1998 U.S.-Russia Presidential Summit, the then Chairman of the RF SCC, Valery Draganov, highlighted the illicit trafficking challenge confronting Russia and requested U.S. assistance. Since 1991, a myriad of cases associated with the diversion and recovery of nuclear materials appear to be linked to the FSU. In the majority of cases, the material's origin was attributed to Russia. With more than 20,000 km of border contiguous to fourteen other countries, and more than 350 customs and border sites, addressing the threat posed by nuclear smuggling in Russia is not only an urgent but also an expansive problem requiring joint U

  12. 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.

  13. 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.

  14. A comparison of computational models with and without genotyping for prediction of response to second-line HIV therapy

    NARCIS (Netherlands)

    Revell, A. D.; Boyd, M. A.; Wang, D.; Emery, S.; Gazzard, B.; Reiss, P.; van Sighem, A. I.; Montaner, J. S.; Lane, H. C.; Larder, B. A.

    2014-01-01

    We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first-line virological failure. Two sets of models predicted virological response for 99 three-drug regimens for patients on a failing

  15. Cetuximab Concomitant with Second-Line Radiation Therapy in Patients with Locally Advanced Recurrent Squamous Cell Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Muge Akmansu

    2010-12-01

    Full Text Available We presented 9 recurrent head and neck carcinoma patients. Priorly all of them had received radiochemotherapy. We used cetuximab and irradiation concomitantly. Overall survival analysis of the patients was performed using the Kaplan-Meier method on SPSS version 15.0. Based on this calculation, mean follow-up duration is 12.8 months. Mean survival time is 19.8 months and annual mean survival rate is 59.3%.

  16. Phase II Study of Biweekly Pemetrexed Plus Irinotecan as Second-Line Therapy for Metastatic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    C. Louvet

    2010-01-01

    Conclusion. Pemetrexed plus irinotecan administered every two weeks is an active and well-tolerated regimen in mCRC patients pretreated with FOLFOX regimen. However, this regimen does not seem to provide clinically relevant advantage over historical data of a classical FOLFIRI regimen.

  17. The extension of quadrupled xed point results in K-metric spaces

    Directory of Open Access Journals (Sweden)

    Ghasem Soleimani Rad

    2014-05-01

    Full Text Available Recently, Rahimi et al. [Comp. Appl. Math. 2013, In press] dened the conceptof quadrupled xed point in K-metric spaces and proved several quadrupled  xed point theorems for solid cones on K-metric spaces. In this paper some quadrupled xed point results for T-contraction on K-metric spaces without normality condition are proved. Obtained results extend and generalize well-known comparable results in the literature.

  18. V379 Cephei: a quadruple system of two binaries

    Czech Academy of Sciences Publication Activity Database

    Harmanec, P.; Mayer, P.; Prša, A.; Božić, H.; Eenens, P.; Guinan, E. F.; McCook, G.; Koubský, Pavel; Ruždjak, D.; Engle, S.; Sudar, D.; Škoda, Petr; Šlechta, Miroslav; Wolf, M.; Yang, S.

    2007-01-01

    Roč. 463, č. 3 (2007), s. 1061-1069 ISSN 0004-6361 R&D Projects: GA ČR GA205/03/0788; GA ČR GA205/06/0584 Grant - others:US National Science Foundation(US) NSF/RUI AST-0507536. Institutional research plan: CEZ:AV0Z10030501 Source of funding: V - iné verejné zdroje Keywords : V379 Cep * quadruple systems Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.259, year: 2007

  19. Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

    DEFF Research Database (Denmark)

    Schønnemann, K R; Yilmaz, Mette Karen; Bjerregaard, J K

    2012-01-01

    The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.......The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma....

  20. Second Line of Defense, Port of Buenos Aires and Exolgan Container Terminal Operational Testing and Evaluation Plan, Buenos Aires, Argentina

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Bryan W.

    2012-08-23

    The Office of the Second Line of Defense (SLD) Megaports project team for Argentina will conduct operational testing and evaluation (OT&E) at Exolgan Container Terminal at the Port of Dock Sud from July 16-20, 2012; and at the Port of Buenos Aires from September 3-7, 2012. SLD is installing radiation detection equipment to screen export, import, and transshipment containers at these locations. The purpose of OT&E is to validate and baseline an operable system that meets the SLD mission and to ensure the system continues to perform as expected in an operational environment with Argentina Customs effectively adjudicating alarms.

  1. Preparation of supramolecular polymers by copolymerization of monomers containing quadruple hydrogen bonding units with regular monomers

    NARCIS (Netherlands)

    2004-01-01

    The invention relates to the synthesis of polymers containing self-complementary quadruple hydrogen groups by copolymerizing monomers containing a quadruple hydrogen bonding group with one or more monomers of choice. The resulting polymers show unique new characteristics due to the presence of

  2. Preparation of supramolecular polymers by copolymerization of monomers containing quadruple hydrogen bonding units with regular monomers

    NARCIS (Netherlands)

    2004-01-01

    The invention relates to the synthesis of polymers contg. self-complementary quadruple H groups by copolymg. monomers contg. a quadruple H bonding group with ³1 monomers of choice. The resulting polymers show unique new characteristics due to the presence of addnl. phys. interactions between the

  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. Second-Line Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian, Tubal and Peritoneal Cancer: A Propensity Score-Matching Study.

    Science.gov (United States)

    Lu, Chien-Hsing; Chang, Yen-Hou; Lee, Wai-Hou; Chang, Yi; Peng, Chia-Wen; Chuang, Chi-Mu

    2016-01-01

    The superiority of frontline intraperitoneal (IP) over intravenous (IV) chemotherapy is well established in the treatment of epithelial ovarian cancer. However, the role of IP chemotherapy in the second-line setting has rarely been investigated. Consecutive patients diagnosed with recurrent epithelial, tubal and peritoneal cancers between January 2000 and December 2012 were recruited using a propensity score-matching technique to adjust relevant risk factors. In total, 310 patients were included in the final analysis (94 for platinum-refractory/resistant disease and 216 for platinum-sensitive disease). IP chemotherapy demonstrated significantly longer median progression-free survival than IV chemotherapy (4.9 vs. 2.4 months, p chemotherapy confers longer progression-free survival than IV chemotherapy. Large-scale clinical trials should be conducted to validate the true efficacy. © 2016 S. Karger AG, Basel.

  5. Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

    Science.gov (United States)

    Luealon, Phanida; Khempech, Nipon; Vasuratna, Apichai; Hanvoravongchai, Piya; Havanond, Piyalamporn

    2016-01-01

    There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All

  6. Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

    2014-05-01

    At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  7. Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

    Science.gov (United States)

    Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

    2014-06-01

    To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

  8. Quadruple Cone Coil with improved focality than Figure-8 coil in Transcranial Magnetic Stimulation

    Science.gov (United States)

    Rastogi, Priyam; Lee, Erik G.; Hadimani, Ravi L.; Jiles, David C.

    Transcranial Magnetic Stimulation (TMS) is a non-invasive therapy which uses a time varying magnetic field to induce an electric field in the brain and to cause neuron depolarization. Magnetic coils play an important role in the TMS therapy since their coil geometry determines the focality and penetration's depth of the induced electric field in the brain. Quadruple Cone Coil (QCC) is a novel coil with an improved focality when compared to commercial Figure-8 coil. The results of this newly designed QCC coil are compared with the Figure-8 coil at two different positions of the head - vertex and dorsolateral prefrontal cortex, over the 50 anatomically realistic MRI derived head models. Parameters such as volume of stimulation, maximum electric, area of stimulation and location of maximum electric field are determined with the help of computer modelling of both coils. There is a decrease in volume of brain stimulated by 11.6 % and a modest improvement of 8 % in the location of maximum electric field due to QCC in comparison to the Figure-8 coil. The Carver Charitable Trust and The Galloway Foundation.

  9. Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.

    Science.gov (United States)

    Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Marrone, N; Ortiz, E H; Leone, B A; Vallejo, C T; Machiavelli, M R; Romero, A O

    1998-08-01

    A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.

  10. Sensitivity Pattern of Second Line Anti-Tuberculosis Drugs against Clinical Isolates of Multidrug Resistant Mycobacterium Tuberculosis

    International Nuclear Information System (INIS)

    Ghafoor, T.; Ikram, A.; Abbasi, S. A.; Zaman, G.; Ayyub, M.; Palomino, J. C.; Vandamme, P.; Martin, A.

    2015-01-01

    Objective:To determine the current sensitivity pattern of second line anti-tuberculosis drugs against clinical isolates of Multidrug Resistant Mycobacterium tuberculosis (MDR-TB). Study Design: A cross-sectional study. Place and Duration of Study: Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from November 2011 to April 2013. Methodology: Samples received during the study period were processed on BACTEC MGIT 960 system for Mycobacterium tuberculosis (MTB) culture followed by first line drugs susceptibility testing of culture proven MTB isolates. On the basis of resistance to rifampicin and isoniazid, 100 clinical isolates of MDR-TB were further subjected to susceptibility testing against amikacin (AMK), capreomycin (CAP), ofloxacin (OFL) and ethionamide (ETH) as per standard BACTEC MGIT 960 instructions. Results: Out of 100 MDR-TB isolates, 62% were from male patients and 38% from female patients. 97% were sensitive to AMK, 53% to OFL, 87% to CAP; and 87% were sensitive to ETH. Conclusion: The majority of the MDR-TB isolates showed excellent sensitivity against AMK, CAP and ETH. However, sensitivity of MDR-TB isolates against fluoroquinolones like OFL was not encouraging. (author)

  11. Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

    Science.gov (United States)

    Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

    2005-10-01

    Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

  12. Optimal Design of a Center Support Quadruple Mass Gyroscope (CSQMG

    Directory of Open Access Journals (Sweden)

    Tian Zhang

    2016-04-01

    Full Text Available This paper reports a more complete description of the design process of the Center Support Quadruple Mass Gyroscope (CSQMG, a gyro expected to provide breakthrough performance for flat structures. The operation of the CSQMG is based on four lumped masses in a circumferential symmetric distribution, oscillating in anti-phase motion, and providing differential signal extraction. With its 4-fold symmetrical axes pattern, the CSQMG achieves a similar operation mode to Hemispherical Resonant Gyroscopes (HRGs. Compared to the conventional flat design, four Y-shaped coupling beams are used in this new pattern in order to adjust mode distribution and enhance the synchronization mechanism of operation modes. For the purpose of obtaining the optimal design of the CSQMG, a kind of applicative optimization flow is developed with a comprehensive derivation of the operation mode coordination, the pseudo mode inhibition, and the lumped mass twisting motion elimination. The experimental characterization of the CSQMG was performed at room temperature, and the center operation frequency is 6.8 kHz after tuning. Experiments show an Allan variance stability 0.12°/h (@100 s and a white noise level about 0.72°/h/√Hz, which means that the CSQMG possesses great potential to achieve navigation grade performance.

  13. A child with acute encephalopathy associated with quadruple viral infection

    Directory of Open Access Journals (Sweden)

    Keiko eNakata

    2015-04-01

    Full Text Available infection does not always result in AE. The risk factors for developing infantile AE upon such infection remain to be determined. Here we report an infant with AE coinfected with human herpesvirus 6 (HHV-6 and three picornaviruses: coxsackievirus A6 (CVA6, enterovirus D68 (EV-D68, and human parechovirus (HPeV. EV-D68 was vertically transmitted to the infant from his mother. CVA6 and HPeV were likely transmitted to the infant at the nursery school. HHV-6 might have been re-activated in the patient. It remains undetermined which pathogen played the central role in the AE pathogenesis. However, active, simultaneous infection by four viruses likely evoke a cytokine storm, leading to the pathogenesis of AE. Conclusion: Infant cases with active quadruple infection by potentially AE-causing viruses have seldom been reported, partly because systematic nucleic acid-based laboratory tests on picornaviruses are not common. We propose that simultaneous viral infection may serve as a risk factor for the development of AE.

  14. Update on quadruple suspension design for Advanced LIGO

    International Nuclear Information System (INIS)

    Aston, S M; Carbone, L; Cutler, R M; Hoyland, D; Barton, M A; Bland, B; Bell, A S; Beveridge, N; Cagnoli, G; Cantley, C A; Cumming, A V; Cunningham, L; Hammond, G D; Haughian, K; Hough, J; Brummitt, A J; Greenhalgh, R J S; Hayler, T M; Heptonstall, A; Heefner, J

    2012-01-01

    We describe the design of the suspension systems for the major optics for Advanced LIGO, the upgrade to LIGO—the Laser Interferometric Gravitational-Wave Observatory. The design is based on that used in GEO600—the German/UK interferometric gravitational wave detector, with further development to meet the more stringent noise requirements for Advanced LIGO. The test mass suspensions consist of a four-stage or quadruple pendulum for enhanced seismic isolation. To minimize suspension thermal noise, the final stage consists of a silica mirror, 40 kg in mass, suspended from another silica mass by four silica fibres welded to silica ears attached to the sides of the masses using hydroxide-catalysis bonding. The design is chosen to achieve a displacement noise level for each of the seismic and thermal noise contributions of 10 −19 m/√Hz at 10 Hz, for each test mass. We discuss features of the design which has been developed as a result of experience with prototypes and associated investigations. (paper)

  15. 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

  16. Sandwich-type tetrakis(phthalocyaninato) dysprosium-cadmium quadruple-decker SMM.

    Science.gov (United States)

    Wang, Hailong; Qian, Kang; Wang, Kang; Bian, Yongzhong; Jiang, Jianzhuang; Gao, Song

    2011-09-14

    Homoleptic tetrakis[2,3,9,10,16,17,23,24-octa(butyloxy)phthalocyaninato] dysprosium-cadmium quadruple-decker complex 1 was isolated in relatively good yield of 43% from a simple one-pot reaction. This compound represents the first sandwich-type tetrakis(phthalocyaninato) rare earth-cadmium quadruple-decker SMM that has been structurally characterized. This journal is © The Royal Society of Chemistry 2011

  17. Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa.

    Science.gov (United States)

    Simmons, Bryony; Hill, Andrew; Ford, Nathan; Ruxrungtham, Kiat; Ananworanich, Jintanat

    2014-01-01

    Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. HIV drug prices used in national programmes (2010-2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (psub-Saharan Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74-541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.

  18. 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

  19. The closest M-dwarf quadruple system to the Sun

    International Nuclear Information System (INIS)

    Davison, Cassy L.; White, R. J.; Jao, W.-C.; Henry, T. J.; Quinn, S. N.; Cantrell, J. R.; Winters, J. G.; Bailey, J. I. III; Riedel, A. R.; Subasavage, J. P.; Crockett, C. J.

    2014-01-01

    We report new infrared radial velocity measurements obtained with CSHELL at NASA's Infrared Telescope Facility that reveal the M3.5 dwarf GJ 867B to be a single-lined spectroscopic binary with a period of 1.795 ± 0.017 days. Its velocity semi-amplitude of 21.4 ± 0.5 km s –1 corresponds to a minimum mass of 61 ± 7 M JUP ; the new companion, which we call GJ 867D, could be a brown dwarf. Stable astrometric measurements of GJ 867BD obtained with CTIO's 0.9 m telescope over the last decade exclude the presence of any massive planetary companions (7-18 M JUP ) with longer orbital periods (2-10 yr) for the majority of orientations. These complementary observations are also used to determine the trigonometric distance and proper motion of GJ 867BD; the measurements are consistent with the HIPPARCOS measured values of the M2 dwarf GJ 867AC, which is itself a 4.1 day double-lined spectroscopic binary at a projected separation of 24.''5 (216 AU) from GJ 867BD. These new measurements strengthen the case that GJ 867AC and GJ 867BD are physically associated, making the GJ 867 system one of only four quadruple systems within 10 pc of the Sun (d = 8.82 ± 0.08 pc) and the only among these with all M-dwarf (or cooler) components.

  20. Pattern optimizing verification of self-align quadruple patterning

    Science.gov (United States)

    Yamato, Masatoshi; Yamada, Kazuki; Oyama, Kenichi; Hara, Arisa; Natori, Sakurako; Yamauchi, Shouhei; Koike, Kyohei; Yaegashi, Hidetami

    2017-03-01

    Lithographic scaling continues to advance by extending the life of 193nm immersion technology, and spacer-type multi-patterning is undeniably the driving force behind this trend. Multi-patterning techniques such as self-aligned double patterning (SADP) and self-aligned quadruple patterning (SAQP) have come to be used in memory devices, and they have also been adopted in logic devices to create constituent patterns in the formation of 1D layout designs. Multi-patterning has consequently become an indispensible technology in the fabrication of all advanced devices. In general, items that must be managed when using multi-patterning include critical dimension uniformity (CDU), line edge roughness (LER), and line width roughness (LWR). Recently, moreover, there has been increasing focus on judging and managing pattern resolution performance from a more detailed perspective and on making a right/wrong judgment from the perspective of edge placement error (EPE). To begin with, pattern resolution performance in spacer-type multi-patterning is affected by the process accuracy of the core (mandrel) pattern. Improving the controllability of CD and LER of the mandrel is most important, and to reduce LER, an appropriate smoothing technique should be carefully selected. In addition, the atomic layer deposition (ALD) technique is generally used to meet the need for high accuracy in forming the spacer film. Advances in scaling are accompanied by stricter requirements in the controllability of fine processing. In this paper, we first describe our efforts in improving controllability by selecting the most appropriate materials for the mandrel pattern and spacer film. Then, based on the materials selected, we present experimental results on a technique for improving etching selectivity.

  1. The Relationship between Preeclampsia and Quadruple Screening Test in Nuliparous

    Directory of Open Access Journals (Sweden)

    Farnaz Zand Vakili

    2017-01-01

    Full Text Available Introduction: Early diagnosis and prediction of preeclampsia needs appropriate obstetric care. Preeclampsia predicting methods are important. This study was designed to determine the correlation between preeclampsia and quadruple screening test in the nulliparous. Materials and Methods:  This case - control study was conducted on 54 pregnant women with preeclampsia (case group and 108 healthy pregnant women (control group who referred to health centers in Sanandaj, Iran. Ultrasonography was performed to determine the gestational age by a radiologist. Maternal serum levels of alpha fetoprotein (AFP, human chorionic gonadotropin (hCG, unconjugated estriol (uE3, and inhibin-A were measured in the second trimester of pregnancy. Data were analyzed using SPSS statistical software and Chi-square test, T-test, sensitivity, specificity, positive and negative predictive values. Results: The results showed that the sensitivity and specificity for the diagnosis of preeclampsia in pregnant women for hCG were 35.2% and 79.6 respectively. These findings for estriol were 20.4% and 88.9%, for inhibin-A were 38.8% and 88% and for alpha fetoprotein were 38.8% and 74.1%. The positive predictive value for hCG, estriol, inhibin-A and alpha fetoprotein were 46.3%, 47.8%, 61.8% and 42.9% respectively. The negative predictive value for hCG, estriol, inhibin-A and alpha fetoprotein were also 71%, 69.1%, 74.2% and 70.8% respectively. Conclusion: There was a relationship between preeclampsia and high levels of inhibin-A and hCG. Further studies on these markers and evaluating their usefulness in the diagnosis and management of preeclampsia are recommended.

  2. Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

    Science.gov (United States)

    Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

    2012-01-01

    in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment. PMID:22792406

  3. Evaluation of the Sensititre MycoTB plate for susceptibility testing of the Mycobacterium tuberculosis complex against first- and second-line agents.

    Science.gov (United States)

    Hall, Leslie; Jude, Kurt P; Clark, Shirley L; Dionne, Kim; Merson, Ryan; Boyer, Ana; Parrish, Nicole M; Wengenack, Nancy L

    2012-11-01

    The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.

  4. A clinical trial protocol for second line treatment of malignant brain tumors with BNCT at University of Tsukuba

    Energy Technology Data Exchange (ETDEWEB)

    Aiyama, H. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Nakai, K., E-mail: knakai@Neurosurg-tsukuba.com [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Yamamoto, T. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan)] [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Nariai, T. [Department of Neurosurgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyouku (Japan); Kumada, H. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Ishikawa, E. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Isobe, T. [Department of Radiation Oncology, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan); Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba (Japan)

    2011-12-15

    We have evaluated the efficacy and safety of boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor using a new protocol. One of the two patients enrolled in this trial is a man with recurrent glioblastoma and the other is a woman with anaplastic meningioma. Both are still alive and no severe adverse events have been observed. Our findings suggest that NCT will be safe as a palliative therapy for malignant brain tumors. - Highlights: Black-Right-Pointing-Pointer Boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor. Black-Right-Pointing-Pointer Two cases with recurrent glioblastoma and anaplastic meningioma. Black-Right-Pointing-Pointer No severe adverse events have been observed using BNCT. Black-Right-Pointing-Pointer BNCT has a possibility of a safe palliative therapy for malignant brain tumors.

  5. A clinical trial protocol for second line treatment of malignant brain tumors with BNCT at University of Tsukuba

    International Nuclear Information System (INIS)

    Aiyama, H.; Nakai, K.; Yamamoto, T.; Nariai, T.; Kumada, H.; Ishikawa, E.; Isobe, T.; Endo, K.; Takada, T.; Yoshida, F.; Shibata, Y.; Matsumura, A.

    2011-01-01

    We have evaluated the efficacy and safety of boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor using a new protocol. One of the two patients enrolled in this trial is a man with recurrent glioblastoma and the other is a woman with anaplastic meningioma. Both are still alive and no severe adverse events have been observed. Our findings suggest that NCT will be safe as a palliative therapy for malignant brain tumors. - Highlights: ► Boron neutron capture therapy (BNCT) for recurrent glioma and malignant brain tumor. ► Two cases with recurrent glioblastoma and anaplastic meningioma. ► No severe adverse events have been observed using BNCT. ► BNCT has a possibility of a safe palliative therapy for malignant brain tumors.

  6. [Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

    Science.gov (United States)

    Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

    2015-06-01

    This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

  7. Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Shuyang YAO

    2015-06-01

    Full Text Available Background and objective This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed in previously treated advanced non-small cell lung cancer (NSCLC. Methods Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS was evaluated by Kaplan-Meier method. Results Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR (28.1% vs 18.2%, P=0.341, disease control rate (DFS(43.8% vs 45.5%, P=0.890, and PFS (4.3 months vs 3.8 months, P=0.506. In the icotinib group, the ORR of epidermal growth factor receptor (EGFR mutant was significantly higher than that of EGFR unknown or wild type (P=0.017. In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001. Conclusion Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

  8. Simulation of growing grains under orientation relation - dependent quadruple point dragging

    International Nuclear Information System (INIS)

    Ito, K

    2015-01-01

    The growth behaviour of a specified grain embedded in matrix grains, for which the migration mobility of the quadruple points depended on the relation between the orientations of the growing and shrinking grains, was studied using a modified Potts MC-type threedimensional simulation. Large embedded grains continued to grow without being overcome by coarsening matrix grains, whereas small embedded grains disappeared, under the influence of the relative mobilities of the quadruple points, the composition of the matrix grain texture and the width of the grain size distribution of the matrix grains. These results indicate that orientation relation-dependent quadruple point dragging can affect the recrystallization texture during the grain coarsening stage. (paper)

  9. The Quadruple Helix Model Enhancing Innovative Performance Of Indonesian Creative Industry

    Directory of Open Access Journals (Sweden)

    Sri Wahyu Lelly Hana Setyanti

    2017-11-01

    Full Text Available The creative industry in Indonesia has contributed positively to the national economic growth. Creative industry grows from the creativity and innovation performance of the business actors. The challenge of creative industry is how to completely understand the creative and innovative processes in business management. Therefore it requires an approach that combines the synergy between academicians entrepreneurs government and society in a quadruple helix model. The objective of this research is to develop a creativity model through a quadruple helix model in improving innovation performance of the creative industry.

  10. Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011.

    Science.gov (United States)

    Nguyen, Hoa Binh; Nguyen, Nhung Viet; Tran, Huong Thi Giang; Nguyen, Hai Viet; Bui, Quyen Thi Tu

    2016-01-01

    Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

  11. A population-based study of first and second-line drug-resistant tuberculosis in a high-burden area of the Mexico/United States border

    Directory of Open Access Journals (Sweden)

    Pola Becerril-Montes

    2013-04-01

    Full Text Available The resistance of 139 Mycobacterium tuberculosis (MTB isolates from the city of Monterrey, Northeast Mexico, to first and second-line anti-TB drugs was analysed. A total of 73 isolates were susceptible and 66 were resistant to anti-TB drugs. Monoresistance to streptomycin, isoniazid (INH and ethambutol was observed in 29 cases. Resistance to INH was found in 52 cases and in 29 cases INH resistance was combined with resistance to two or three drugs. A total of 24 isolates were multidrug-resistant (MDR resistant to at least INH and rifampicin and 11 MDR cases were resistant to five drugs. The proportion of MDR-TB among new TB cases in our target population was 0.72% (1/139 cases. The proportion of MDR-TB among previously treated cases was 25.18% (35/139 cases. The 13 polyresistant and 24 MDR isolates were assayed against the following seven second-line drugs: amikacin (AMK, kanamycin (KAN, capreomycin (CAP, clofazimine (CLF, ethionamide (ETH, ofloxacin (OFL and cycloserine (CLS. Resistance to CLF, OFL or CLS was not observed. Resistance was detected to ETH (10.80% and to AMK (2.70%, KAN (2.70% and CAP (2.70%. One isolate of MDR with primary resistance was also resistant to three second-line drugs. Monterrey has a high prevalence of MDR-TB among previously treated cases and extensively drug-resistant-MTB strains may soon appear.

  12. 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.

  13. The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

    2018-04-01

    year were $34,141, $19,371, and $17,506 higher, respectively. Everolimus had similar OS and lower costs compared with axitinib. The additional cost per month of OS was $48,773 for cabozantinib and $24,214 for nivolumab versus everolimus. The additional treatment cost with cabozantinib, nivolumab, or axitinib versus everolimus for each additional month of PFS was estimated at $21,338, $64,570, and $35,012, respectively. Over 2 years, the additional costs per additional month of OS for nivolumab and axitinib versus everolimus were similar to the 1-year analysis; for cabozantinib, the cost was lower. Results were sensitive to changes in mean OS, mean PFS, therapy duration, and drug costs estimates. Everolimus for second-line mRCC was associated with similar OS and lower costs compared with axitinib over 1- and 2-year horizons. The additional cost per additional month of OS and PFS associated with cabozantinib or nivolumab versus everolimus creates a metric for evaluating the cost of second-line therapies in relation to their respective treatment effects. Funding for this research was provided by Novartis, which was involved in all stages of study research and manuscript preparation. Ghate and Perez are employees of Novartis and own stock/stock options. Swallow, Messali, McDonald, and Duchesneau are employees of Analysis Group, which has received consultancy fees from Novartis. Study concept and design were contributed by Swallow, Messali, Ghate, and Perez, along with McDonald and Duchesneau. Swallow, Messali, McDonald, and Duchesneau collected the data, and all authors participated in data interpretation. The manuscript was written by Swallow, Messali, and Ghate, along with the other authors, and revised by Swallow, Messali, Ghate, and Perez. A synopsis of the current research was presented in poster format at the 15th International Kidney Cancer Symposium on November 4-5, 2016, in Miami, Florida.

  14. A new quadruple gravitational lens system : CLASS B0128+437

    NARCIS (Netherlands)

    Phillips, PM; Norbury, MA; Koopmans, LVE; Browne, IWA; Jackson, NJ; Wilkinson, PN; Biggs, AD; Blandford, RD; de Bruyn, AG; Fassnacht, CD; Helbig, P; Mao, S; Marlow, DR; Myers, ST; Pearson, TJ; Readhead, ACS; Rusin, D; Xanthopoulos, E

    2000-01-01

    High-resolution MERLIN observations of a newly discovered four-image gravitational lens system, B0128+437, are presented. The system was found after a careful re-analysis of the entire CLASS data set. The MERLIN observations resolve four components in a characteristic quadruple-image configuration;

  15. Control the length of beam trajectory with a quadruple triplet for heavy ion accelerator

    International Nuclear Information System (INIS)

    Zhang, Zhan; Wei, Shaoqing; Lee, Sang Jin; Kim, Do Gyun; Kim, Jang Youl

    2016-01-01

    Beam trajectory is needed to be controlled in heavy ion accelerator system. Quadruple magnets are widely used in heavy ion accelerator for focusing the transporting particles. A quadruple triplet system which consists of three consecutive quadrupoles, Q1, Q2 and Q3, is used to control beam trajectory at a focused position. Q1 and Q3 have symmetry with respect to Q2. The beam trajectory in magnet system is affected by higher order fields existed in real fields. For quadrupoles, the representation simulation of beam trajectory was carried out to study the beam trajectory and to estimate an effect of higher order field in triplet system. SCALA program was used to simulate the beam trajectory in OperaTM. SCALA can analyze a large number of beam trajectories at the same time by adjusting the size of finite element of the emitter. With OperaTM and MatlabTM programs, the position of focused beam spot in quadruple triplet system can be increased or decreased using evolution strategy (ES) method, therefore the length of triplet system can be controlled. Finally, the quadruple triplet system with the appropriate length and expected beam spot range was suggested in this paper

  16. Control the length of beam trajectory with a quadruple triplet for heavy ion accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhan; Wei, Shaoqing; Lee, Sang Jin [Uiduk University, Gyeongju (Korea, Republic of); Kim, Do Gyun; Kim, Jang Youl [Rare Isotope Science Project, Institute for Basic Science, Daejeon (Korea, Republic of)

    2016-12-15

    Beam trajectory is needed to be controlled in heavy ion accelerator system. Quadruple magnets are widely used in heavy ion accelerator for focusing the transporting particles. A quadruple triplet system which consists of three consecutive quadrupoles, Q1, Q2 and Q3, is used to control beam trajectory at a focused position. Q1 and Q3 have symmetry with respect to Q2. The beam trajectory in magnet system is affected by higher order fields existed in real fields. For quadrupoles, the representation simulation of beam trajectory was carried out to study the beam trajectory and to estimate an effect of higher order field in triplet system. SCALA program was used to simulate the beam trajectory in OperaTM. SCALA can analyze a large number of beam trajectories at the same time by adjusting the size of finite element of the emitter. With OperaTM and MatlabTM programs, the position of focused beam spot in quadruple triplet system can be increased or decreased using evolution strategy (ES) method, therefore the length of triplet system can be controlled. Finally, the quadruple triplet system with the appropriate length and expected beam spot range was suggested in this paper.

  17. EPIC 219217635: A Doubly Eclipsing Quadruple System Containing an Evolved Binary

    DEFF Research Database (Denmark)

    Borkovits, T.; Albrecht, S.; Rappaport, S.

    2018-01-01

    We have discovered a doubly eclipsing, bound, quadruple star system in the field of K2 Campaign 7. EPIC 219217635 is a stellar image with Kp = 12.7 that contains an eclipsing binary (‘EB’) with PA = 3.59470 d and a second EB with PB = 0.61825 d. We have obtained followup radial-velocity (‘RV’) sp...

  18. Filterless low-phase-noise frequency-quadrupled microwave generation based on a multimode optoelectronic oscillator

    Science.gov (United States)

    Teng, Yichao; Zhang, Pin; Zhang, Baofu; Chen, Yiwang

    2018-02-01

    A scheme to realize low-phase-noise frequency-quadrupled microwave generation without any filter is demonstrated. In this scheme, a multimode optoelectronic oscillator is mainly contributed by dual-parallel Mach-Zehnder modulators, fiber, photodetector, and microwave amplifier. The local source signal is modulated by a child MZM (MZMa), which is worked at maximum transmission point. Through properly adjusting the bias voltages of the other child MZM (MZMb) and the parent MZM (MZMc), optical carrier is effectively suppressed and second sidebands are retained, then the survived optical signal is fed back to the photodetector and MZMb to form an optoelectronic hybrid resonator and realize frequency-quadrupled signal generation. Due to the high Q-factor and mode selection effect of the optoelectronic hybrid resonator, compared with the source signal, the generated frequency-quadrupled signal has a lower phase noise. The approach has verified by experiments, and 18, 22, and 26 GHz frequency-quadrupled signal are generated by 4.5, 5.5, and 6.5 GHz local source signals. Compared with 4.5 GHz source signal, the phase noise of generated 18 GHz signal at 10 kHz frequency offset has 26.5 dB reduction.

  19. SESOTHO trial (“Switch Either near Suppression Or THOusand”) – switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa

    OpenAIRE

    Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy Renée; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

    2018-01-01

    Background The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-...

  20. Dynamics of quadruple systems composed of two binaries: stars, white dwarfs, and implications for Ia supernovae

    Science.gov (United States)

    Fang, Xiao; Thompson, Todd A.; Hirata, Christopher M.

    2018-05-01

    We investigate the long-term secular dynamics and Lidov-Kozai (LK) eccentricity oscillations of quadruple systems composed of two binaries at quadrupole and octupole orders in the perturbing Hamiltonian. We show that the fraction of systems reaching high eccentricities is enhanced relative to triple systems, over a broader range of parameter space. We show that this fraction grows with time, unlike triple systems evolved at quadrupole order. This is fundamentally because with their additional degrees of freedom, quadruple systems do not have a maximal set of commuting constants of the motion, even in secular theory at quadrupole order. We discuss these results in the context of star-star and white dwarf-white dwarf (WD) binaries, with emphasis on WD-WD mergers and collisions relevant to the Type Ia supernova problem. For star-star systems, we find that more than 30 per cent of systems reach high eccentricity within a Hubble time, potentially forming triple systems via stellar mergers or close binaries. For WD-WD systems, taking into account general relativistic and tidal precession and dissipation, we show that the merger rate is enhanced in quadruple systems relative to triple systems by a factor of 3.5-10, and that the long-term evolution of quadruple systems leads to a delay-time distribution ˜1/t for mergers and collisions. In gravitational wave-driven mergers of compact objects, we classify the mergers by their evolutionary patterns in phase space and identify a regime in about 8 per cent of orbital shrinking mergers, where eccentricity oscillations occur on the general relativistic precession time-scale, rather than the much longer LK time-scale. Finally, we generalize previous treatments of oscillations in the inner binary eccentricity (evection) to eccentric mutual orbits. We assess the merger rate in quadruple and triple systems and the implications for their viability as progenitors of stellar mergers and Type Ia supernovae.

  1. Associations between deepness of response and clinical outcomes among Japanese patients with metastatic colorectal cancer treated with second-line FOLFIRI plus cetuximab

    Directory of Open Access Journals (Sweden)

    Osumi H

    2015-08-01

    Full Text Available Hiroki Osumi, Satoshi Matsusaka, Mitsukuni Suenaga, Eiji Shinozaki, Nobuyuki Mizunuma Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan Background: In the FIRE-3 trial, overall survival (OS was significantly longer in patients treated with FOLFIRI plus cetuximab (C-mab than in those treated with FOLFIRI plus bevacizumab (Bev, but progression-free survival (PFS was not significantly different. This may be associated with the deepness of response (DpR in patients treated with FOLFIRI plus C-mab. We aimed to evaluate the relationship between clinical outcome and DpR in metastatic colorectal cancer (mCRC patients treated with second-line FOLFIRI plus C-mab.Methods: A total of 112 patients with histopathologically confirmed mCRC treated with second-line FOLFIRI in combination with C-mab (N=42 or Bev (N=70 were retrospectively enrolled between October 2008 and June 2013. The relationship between DpR and clinical outcome in patients treated with FOLFIRI plus C-mab or Bev was determined.Results: Forty-two patients treated with FOLFIRI plus C-mab had a mean DpR of 6.1% (interquartile range: -13.7%, 20.8% and a minimum DpR of -62.7%. On the other hand, 70 patients treated with FOLFIRI plus Bev had a mean DpR of 0% (interquartile range: -16%, 10% and a minimum DpR of -111%. DpR ≥30% was associated with significantly longer OS and PFS when compared with DpR ≤30% in patients given FOLFIRI plus C-mab. DpR (≥30% was independently associated with prolongation of OS and PFS. In patients treated with FOLFIRI plus C-mab, there was a moderate positive correlation between DpR and clinical outcomes (OS: r=0.51, P<0.001; PFS: r=0.54, P<0.001.Conclusion: FOLFIRI plus C-mab yielded a stronger correlation between DpR and clinical outcomes. These results indicate the potential of DpR as a new measure of efficacy in mCRC patients treated with second-line chemotherapy plus C-mab. Keywords: deepness of

  2. Meta-analysis of published efficacy and safety data for docetaxel in second-line treatment of patients with advanced non-small-cell lung cancer.

    Science.gov (United States)

    Stroh, Mark; Green, Michelle; Cha, Edward; Zhang, Nancy; Wada, Russ; Jin, Jin

    2016-03-01

    To gain a better understanding of the impact of dose and other prognostic factors on safety and efficacy of docetaxel in second-line non-small-cell lung cancer patients. A model-based meta-analysis (MBMA) of a published docetaxel monotherapy data in 6085 second-line non-small-cell lung cancer patients from 46 trials was conducted. The logit of grade 3/4 neutropenia incidence was a linear function of dose, with a 5% increase in the odds of neutropenia per mg/m(2) increase in dose [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.04-1.06], and a Japanese study effect (OR 17.1, 95% CI 6.05-48.4). The logit of overall response rate (ORR) was a linear function of cumulative dose (0.4% increase in the odds of response per mg/m(2) increase; OR 1.004, 95% CI 1.001-1.008) and median population age (OR 1.08 per year, 95% CI 1.02-1.15). A Japanese study effect was identified for overall survival (OS) in addition to prognostic factors identified by a previous meta-analysis. This current MBMA identified docetaxel dose-response relationships for both neutropenia and ORR, an effect of age on ORR, and Japanese study effects on both neutropenia and OS.

  3. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

    DEFF Research Database (Denmark)

    Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle

    2006-01-01

    for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses...... (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value...... for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of tetranectin, or high serum levels...

  4. 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.

  5. Effectiveness and tolerability of second-line therapy with vildagliptin versus other oral agents in type 2 diabetes (EDGE): post-hoc subanalysis of the Belgian data.

    Science.gov (United States)

    Hoste, J; Daci, E; Mathieu, C

    2014-06-01

    To assess the efficacy and safety of vildagliptin versus other oral glucose-lowering drugs added to antidiabetic monotherapy in Belgian patients with type 2 diabetes mellitus, in comparison to the global EDGE study results. This is a pre-specified post-hoc subanalysis of the Belgian patient cohort from a worldwide 1-year observational study that compared the effectiveness and tolerability of vildagliptin to other oral antidiabetic agents in type 2 diabetes patients failing monotherapy with oral glucose-lowering agents (EDGE). A total of 1793 Belgian patients were enrolled. Physicians could add any oral antidiabetic drug and patients entered either into the vildagliptin or the comparator cohort. The primary effectiveness and tolerability endpoint was defined as the proportion of patients having a treatment response (HbA1c reduction from baseline to month 12 endpoint >0·3%) without hypoglycemia, weight gain, peripheral oedema, or gastrointestinal side-effects. In the Belgian population, 37·8% of patients in the vildagliptin group and 32·8% in the comparator group had a decrease in HbA1c of >0·3% without the predefined tolerability issues of hypoglycemia, weight gain, oedema or, gastrointestinal complaints (primary endpoint), resulting in an unadjusted odds ratio of 1·24 (95% CI: 0·96-1·61). Mean HbA1c change from baseline was -0·81% in the vildagliptin cohort and -0·75% in the comparator cohort. Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (14·9% versus 14·5% in the compactor group) and serious adverse events (2·7% versus 2·5% in the comparator group). In this EDGE subgroup of Belgian patients with type 2 diabetes who do not achieve the glycemic targets with monotherapy, a similar trend as in the global EDGE study was observed. Adding vildagliptin as a second oral glucose-lowering agent resulted in lowering HbA1c to <7% without weight gain, hypoglycemia or peripheral oedema in a higher proportion of patients than comparator oral antidiabetic drugs, with no differences in the reported number of adverse events.

  6. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

    Directory of Open Access Journals (Sweden)

    Sergio Szyldergemajn

    2009-09-01

    Full Text Available The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2 administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

  7. Application of the RPN methodology for quantification of the operability of the quadruple-tank process

    Directory of Open Access Journals (Sweden)

    J.O. Trierweiler

    2002-04-01

    Full Text Available The RPN indicates how potentially difficult it is for a given system to achieve the desired performance robustly. It reflects both the attainable performance of a system and its degree of directionality. Two new indices, RPN ratio and RPN difference are introduced to quantify how realizable a given desired performance can be. The predictions made by RPN are verified by closed-loop simulations. These indices are applied to quantify the IO-controllability of the quadruple-tank process.

  8. Investigation of shape, position, and permeability of shielding material in quadruple butterfly coil for focused transcranial magnetic stimulation

    Science.gov (United States)

    Rastogi, Priyam; Zhang, Bowen; Tang, Yalun; Lee, Erik G.; Hadimani, Ravi L.; Jiles, David C.

    2018-05-01

    Transcranial magnetic stimulation has been gaining popularity in the therapy for several neurological disorders. A time-varying magnetic field is used to generate electric field in the brain. As the development of TMS methods takes place, emphasis on the coil design increases in order to improve focal stimulation. Ideally reduction of stimulation of neighboring regions of the target area is desired. This study, focused on the improvement of the focality of the Quadruple Butterfly Coil (QBC) with supplemental use of different passive shields. Parameters such as shape, position and permeability of the shields have been explored to improve the focus of stimulation. Results have been obtained with the help of computer modelling of a MRI derived heterogeneous head model over the vertex position and the dorsolateral prefrontal cortex position using a finite element tool. Variables such as maximum electric field induced on the grey matter and scalp, volume and area of stimulation above half of the maximum value of electric field on the grey matter, and ratio of the maximum electric field in the brain versus the scalp have been investigated.

  9. A comparison of individualized treatment guided by VeriStrat with standard of care treatment strategies in patients receiving second-line treatment for advanced non-small cell lung cancer: A cost-utility analysis.

    Science.gov (United States)

    Nelson, Richard E; Stenehjem, David; Akerley, Wallace

    2013-12-01

    Two therapies are appropriate as 2nd-line treatment of non-small cell lung cancer (NSCLC) patients: chemotherapy and epidermal growth factor receptor (EGFR) inhibitor therapy. VeriStrat, a serum proteomic test, can be used to guide treatment decisions for NSCLC patients. The test classifies patients as likely to benefit from either of these two treatment options. The objective of this research was to model the anticipated survival and cost-effectiveness of four different treatment strategies: chemotherapy for all patients (C-all), EGFR inhibitor for all (E-all), a performance status guided selection strategy (PS-guided), and a strategy guided by VeriStrat test results (V-guided). We developed a Markov model with the perspective of the U.S. health care system. Model inputs were taken from published literature for the base-case analysis. One-way and probabilistic sensitivity analyses were performed. The C-all treatment strategy showed the best overall survival outcome (10.1 months), followed by V-guided (9.6 months), PS-guided (9.2 months), and E-all (8.2 months) strategies. The incremental cost-effectiveness ratio (ICER) of a V-guided treatment strategy was $91,111 (vs. E-all) and $8462 (vs. PS-guided) per quality-adjusted life year (QALY). The ICER for C-all compared to V-guided was $105,616. This cost-utility analysis indicates that a treatment strategy guided by the VeriStrat test in patients receiving second-line therapy for NSCLC may experience an overall survival benefit at an incremental cost-effectiveness ratio that is reasonable when compared with other practices, including cancer treatments, generally covered in the U.S. health care system. However, treating all patients with chemotherapy yielded the greatest expected survival. Copyright © 2013. Published by Elsevier Ireland Ltd.

  10. 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.

  11. Molecular characterization of mutations associated with resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients from high prevalence tuberculosis city in Morocco.

    Science.gov (United States)

    Oudghiri, Amal; Karimi, Hind; Chetioui, Fouad; Zakham, Fathiah; Bourkadi, Jamal Eddine; Elmessaoudi, My Driss; Laglaoui, Amin; Chaoui, Imane; El Mzibri, Mohammed

    2018-02-27

    The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global TB control. Although multi drug-resistant tuberculosis (MDR- TB) prevalence and associated genetic mutations in Morocco are well documented, scarce information on XDR TB is available. Hence, the evaluation of pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drugs, is of great value for better management of M/XDR TB in Morocco. To evaluate pre-XDR and XDR prevalence, as well as the mutation status of gyrA, gyrB, rrs, tlyA genes and eis promoter region, associated with resistance to second line drug resistance, in 703 clinical isolates from TB patients recruited in Casablanca, and to assess the usefulness of molecular tools in clinical laboratories for better management of M/XDR TB in Morocco. Drug susceptibility testing (DST) was performed by the proportional method for first line drugs, and then the selected MDR isolates were tested for second line drugs (Ofloxacin, Kanamycin, Amikacin and Capreomycin). Along with DST, all samples were subjected to rpoB, katG and p-inhA mutation analysis by PCR and DNA sequencing. MDR isolates as well as 30 pan-susceptible strains were subjected to PCR and DNA sequencing of gyrA, gyrB, rrs, tlyA genes and eis promoter, associated with resistance to fluoroquinolones and injectable drugs. Among the 703 analysed strains, 12.8% were MDR; Ser531Leu and Ser315Thr being the most common recorded mutations within rpoB and katG genes associated with RIF and INH resistance respectively. Drug susceptibility testing for second line drugs showed that among the 90 MDR strains, 22.2% (20/90) were resistant to OFX, 2.22% (2/90) to KAN, 3.33% (3/90) to AMK and 1.11% (1/90) to CAP. Genotypic analysis revealed that 19 MDR strains harbored mutations in the gyrA gene; the most recorded mutation being Asp91Ala accounting for 47.6% (10

  12. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

    DEFF Research Database (Denmark)

    Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

    2015-01-01

    BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

  13. Time from prior chemotherapy enhances prognostic risk grouping in the second-line setting of advanced urothelial carcinoma: a retrospective analysis of pooled, prospective phase 2 trials.

    Science.gov (United States)

    Sonpavde, Guru; Pond, Gregory R; Fougeray, Ronan; Choueiri, Toni K; Qu, Angela Q; Vaughn, David J; Niegisch, Guenter; Albers, Peter; James, Nicholas D; Wong, Yu-Ning; Ko, Yoo-Joung; Sridhar, Srikala S; Galsky, Matthew D; Petrylak, Daniel P; Vaishampayan, Ulka N; Khan, Awais; Vogelzang, Nicholas J; Beer, Tomasz M; Stadler, Walter M; O'Donnell, Peter H; Sternberg, Cora N; Rosenberg, Jonathan E; Bellmunt, Joaquim

    2013-04-01

    Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) 0, LM, Hb statistic=0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable. Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb advanced UC. These data may facilitate drug development and interpretation of trials. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Should CA-125 response criteria be preferred to response evaluation criteria in solid tumors (RECIST) for prognostication during second-line chemotherapy of ovarian carcinoma?

    DEFF Research Database (Denmark)

    Gronlund, Bo; Høgdall, Claus; Hilden, Jørgen

    2004-01-01

    -line chemotherapy. PATIENTS AND METHODS: From a single-institution registry of 527 consecutive patients with primary ovarian carcinoma, 131 records satisfied the inclusion criteria: ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IC to IV, first-line chemotherapy with paclitaxel...... and a platinum compound, refractory or recurrent disease, and second-line chemotherapy consisting of topotecan or paclitaxel plus carboplatin. Univariate and multivariate analyses of survival were performed using the landmark method. RESULTS: In patients with measurable disease by RECIST and with assessable...... sites (solitary v multiple; hazard ratio, 0.47; P = .020) were identified as contributory prognostic factors for survival, whereas the parameters of RECIST (responders v nonresponders), as well as the remaining variables, had nonsignificant prognostic impact. CONCLUSION: The GCIG CA-125 response...

  15. Metastatic Urothelial Carcinoma with Glandular Differentiation That Confirmed the Response by Autopsy Specimen to Second-Line mFOLFOX6 (Fluorouracil, Oxaliplatin, and Leucovorin plus Bevacizumab Chemotherapy

    Directory of Open Access Journals (Sweden)

    Taku Naiki

    2017-11-01

    Full Text Available The prognostic significance of glandular differentiation in urothelial carcinoma (UC is controversial, and thus far there is no established treatment strategy against metastasis of glandular component. We describe here a case of metastatic UC with glandular differentiation that had histological disappearance of adenocarcinoma components at autopsy after sequential chemotherapy with S-1 and cisplatin (CDDP and with mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin plus bevacizumab (mFOLFOX6+Bev. A 62-year-old Asian male was diagnosed with invasive UC with glandular differentiation (T2N0M0 by radical cystectomy and ileal conduit, and careful follow-up observation was made. Eight years after radical operation, peritoneal metastases occurred, and a biopsy specimen using colon fiber revealed high-grade adenocarcinomas with an immunohistochemical profile that included positivity for cytokeratin 7 (CK7 and negativity for cytokeratin 20 (CK20 and uroplakin, which was identical to the radical cystectomy specimen. Thus, he received combination chemotherapy consisting of S-1 and CDDP; however, the peritoneal metastasis worsened after 2 cycles. Therefore, second-line mFOLFOX6+Bev chemotherapy was performed for a total of 5 courses. In spite of this, the patient died, and the final diagnosis by autopsy was multiple metastases of infiltrating pure UC to the lung, bone, and peritoneum. Interestingly, there were no pathological findings of adenocarcinoma, and the immunohistochemical profile of the metastatic lesions was identical to that of the previous specimens from the bladder and colon. This suggests that sequential chemotherapy of S-1 and CDDP and second-line mFOLFOX6+Bev might be a feasible option in metastatic UC with glandular differentiation.

  16. Extensively and Pre-Extensively Drug Resistant Tuberculosis in Clinical Isolates of Multi-Drug Resistant Tuberculosis Using Classical Second Line Drugs (Levofloxacin and Amikacin)

    International Nuclear Information System (INIS)

    Mirza, I. A.; Khan, F. A.; Khan, K. A.; Satti, L.; Ghafoor, T.; Fayyaz, M.

    2015-01-01

    Objective:To find out the frequency of Extensively Drug Resistant (XDR) and pre-XDR tuberculosis in clinical isolates of Multi-Drug Resistant (MDR) Tuberculosis (TB) by determining the susceptibilities against Levofloxacin and Amikacin (classical second line antituberculosis drugs). Study Design: A descriptive cross-sectional study. Place and Duration of Study: Microbiology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from September 2011 to August 2013. Methodology: Amikacin (AK) and Levofloxacin (LEVO) were obtained in chemically pure form from Sigma (Taufkirchen, Germany). The breakpoint concentration used for AK was 1.0 micro g/ml and for LEVO 2.0 micro g/ml. Mycobacterial Growth Indicator Tube (MGIT) 960 system was used to carry out drug susceptibility testing as per recommended protocol. Results: A total of 3 MDR-TB isolates (3 percentage) turned out to be XDR-TB based upon simultaneous resistance to injectable second line antituberculosis drug AK and one of the fluoro-quinolones (LEVO). A total of 24 MDR-TB isolates (24 percentage) were found to be pre-XDR based upon resistance to LEVO alone. Treatment status record of patients with XDR and pre-XDRTB isolates revealed that majority of patients had received fluoroquinolones (FQs) during the course of treatment. Conclusion: XDR-TB has started to emerge in MDR-TB isolates in our set up. The worrying sign is the high frequency of pre-XDR tuberculosis. Urgent steps need to be taken to stem the tide of pre-XDR-TB in our population. It is thus recommended to develop facilities to carry out drug susceptibility testing to monitor the status of pre-XDR and XDR-TB in our population. (author)

  17. The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

    Science.gov (United States)

    Aguiar, P N; Perry, L A; Penny-Dimri, J; Babiker, H; Tadokoro, H; de Mello, R A; Lopes, G L

    2017-09-01

    Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Influence of vitamin C and E supplementation on the eradication rates of triple and quadruple eradication regimens for Helicobacter pylori infection.

    Science.gov (United States)

    Demirci, Hakan; Uygun İlikhan, Sevil; Öztürk, Kadir; Üstündağ, Yücel; Kurt, Ömer; Bilici, Muammer; Köktürk, Furuzan; Uygun, Ahmet

    2015-11-01

    In our study, we aimed to assess the effect of vitamin E and C supplementation to triple and quadruple Helicobacter pylori eradication regimens. Four hundred patients with H. pylori infection were classified into four groups. Patients in group A (n=100) received amoxicillin, clarithromycin, and lansoprazole for 2 weeks. In group B, patients (n=100) received vitamins C and E for a month, in addition to amoxicillin, clarithromycin, and lansoprazole for 2 weeks. Patients in group C (n=100) received amoxicillin, clarithromycin, lansoprazole, and bismuth subcitrate for 2 weeks, whereas those in group D (n=100) received vitamins C and E for a month, in addition to amoxicillin, clarithromycin, lansoprazole, and bismuth subcitrate for 2 weeks. H. pylori eradication was assessed with the C14 urea breath test 2 months after the end of the therapy. The eradication rate was assessed using per-protocol (PP) and intention-to-treat (ITT) analyses. Three hundred forty-eight patients finished the study. The eradication of H. pylori was achieved in 63 of 84 patients (75%) by PP and 63 of 100 (63%) by ITT analysis in group A, 60 of 84 (71.4%) by PP and 60 of 100 (60%) by ITT analysis in group B, 72 of 89 (80.9 %) by PP and 72 of 100 (72%) by ITT analysis in group C, and 76 of 91 (83.5%) by PP and 76 of 100 (76%) by ITT analysis in group D. There was no remarkable change between groups A and B (p>0.05). Similar results were also found between groups D and C (p>0.05). This study revealed that supplementing vitamins C and E to either the triple or quadruple therapies did not provide an additional advantage for achieving significantly higher eradication rates for H. pylori.

  19. Cost-effectiveness of sunitinib as second-line treatment for gastrointestinal stromal tumor in the People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Li J

    2017-01-01

    Full Text Available Jian Li,1 Hong Ye Ren,2 Juanjuan Zhang,2 Peng Dong,2 Yan Wang,3 Andrea L Stevens,3 Yi Han,3 Min Huang4 1Laboratory of Carcinogenesis and Translational Research for the Ministry of National Education, Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, 2Pfizer Inc., Beijing, People’s Republic of China; 3WG Consulting, New York, NY, USA; 4School of Pharmacy, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Objective: To evaluate the cost-effectiveness of sunitinib as a second-line treatment in patients with advanced gastrointestinal stromal tumors that no longer respond to imatinib 400 mg/d, compared with imatinib 600 mg/d, 800 mg/d, or best supportive care (BSC in the People’s Republic of China. Methods: This study was conducted from the government payer’s perspective with a time horizon of 5 years. Three health states were considered: progression-free survival, disease progression survival, and death, with a cycle length of 6 weeks. Probabilities of disease progression and death were estimated based on survival functions using exponential distribution and progression survival data in the clinical trials. Drug costs were based on drug retail prices and the patient assistance program in the People’s Republic of China, and adverse event management costs were based on published data and/or expert opinion. Uncertainties for parameters in the study were addressed through one-way deterministic and probabilistic sensitivity analysis. Results: When sunitinib was compared with imatinib 600 mg/d and BSC, the incremental cost-effectiveness ratio was RMB75,715 with RMB121,080 per quality-adjusted life-year (QALY gained. Sunitinib demonstrated lower costs and higher QALYs than imatinib 800 mg/d. In the probabilistic sensitivity analysis, the willingness-to-pay per QALY gained was set to be three times the per capita gross domestic product of the People’s Republic of

  20. A Lagrangian framework for deriving triples and quadruples corrections to the CCSD energy

    DEFF Research Database (Denmark)

    Eriksen, Janus Juul; Kristensen, Kasper; Kjærgaard, Thomas

    2014-01-01

    Using the coupled cluster Lagrangian technique, we have determined perturbative corrections to the coupled cluster singles and doubles (CCSD) energy that converge towards the coupled cluster singles, doubles, and triples (CCSDT) and coupled cluster singles, doubles, triples, and quadruples (CCSDTQ......) energies, considering the CCSD state as the unperturbed reference state and the fluctua- tion potential as the perturbation. Since the Lagrangian technique is utilized, the energy corrections satisfy Wigner’s 2n + 1 rule for the cluster amplitudes and the 2n + 2 rule for the Lagrange multi- pliers...

  1. 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

    Background Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Methods Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004–2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997–2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Results Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). Conclusions We found a significant increase in overall survival, PFS, and survival after

  2. 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

    Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to

  3. SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa.

    Science.gov (United States)

    Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy Renée; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

    2018-02-12

    The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL. In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables. The SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART

  4. Seven-day PPI-triple therapy with levofloxacin is very effective for Helicobacter pylori eradication.

    NARCIS (Netherlands)

    Schrauwen, R.W.; Janssen, M.J.R.; Boer, W.A. de

    2009-01-01

    BACKGROUND: Helicobacter pylori infection causes lifelong gastritis and is associated with the development of peptic ulcer disease, MALT lymphoma and gastric cancer. Many patients benefit from H. pylori eradication therapy. PPI-triple therapy is recommended as initial therapy. Quadruple therapy,

  5. A pilot study to assess feasibility of value based pricing in Cyprus through pharmacoeconomic modelling and assessment of its operational framework: sorafenib for second line renal cell cancer.

    Science.gov (United States)

    Petrou, Panagiotis; Talias, Michael A

    2014-01-01

    The continuing increase of pharmaceutical expenditure calls for new approaches to pricing and reimbursement of pharmaceuticals. Value based pricing of pharmaceuticals is emerging as a useful tool and possess theoretical attributes to help health system cope with rising pharmaceutical expenditure. To assess the feasibility of introducing a value-based pricing scheme of pharmaceuticals in Cyprus and explore the integrative framework. A probabilistic Markov chain Monte Carlo model was created to simulate progression of advanced renal cell cancer for comparison of sorafenib to standard best supportive care. Literature review was performed and efficacy data were transferred from a published landmark trial, while official pricelists and clinical guidelines from Cyprus Ministry of Health were utilised for cost calculation. Based on proposed willingness to pay threshold the maximum price of sorafenib for the indication of second line renal cell cancer was assessed. Sorafenib value based price was found to be significantly lower compared to its current reference price. Feasibility of Value Based Pricing is documented and pharmacoeconomic modelling can lead to robust results. Integration of value and affordability in the price are its main advantages which have to be weighed against lack of documentation for several theoretical parameters that influence outcome. Smaller countries such as Cyprus may experience adversities in establishing and sustaining essential structures for this scheme.

  6. Impact of Relational Coordination on Nurse Job Satisfaction, Work Engagement and Burnout: Achieving the Quadruple Aim.

    Science.gov (United States)

    Havens, Donna Sullivan; Gittell, Jody Hoffer; Vasey, Joseph

    2018-03-01

    To explore how relational coordination, known to enhance quality and efficiency outcomes for patients and hospitals, impacts direct care nurse outcomes such as burnout, work engagement, and job satisfaction, addressing the "Quadruple Aim," to improve the experience of providing care. Hospitals are complex organizations in which multiple providers work interdependently, under conditions of uncertainty and time constraints, to deliver safe quality care despite differences in specialization, training, and status. Relational coordination-communicating and relating for the purpose of task integration-is known to improve quality, safety, and efficiency under these conditions, but less is known about its impact on the well-being of direct care providers themselves. Surveys measuring relational coordination among nurses and other types of providers as well as job-related outcomes in 5 acute care community hospitals were completed by direct care RNs. Relational coordination was significantly related to increased job satisfaction, increased work engagement, and reduced burnout. Relational coordination contributes to the well-being of direct care nurses, addressing the Quadruple Aim by improving the experience of providing care.

  7. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS).

    Science.gov (United States)

    Smit, Egbert F; Wu, Yi-Long; Gervais, Radj; Zhou, Caicun; Felip, Enriqueta; Feng, Jifeng; Guclu, Salih Zeki; Hoiczyk, Mathias; Dorokhova, Elena; Freudensprung, Ulrich; Grange, Susan; Perez-Moreno, Pablo Diego; Mitchell, Lada; Reck, Martin

    2016-09-01

    Active smokers with non-small-cell lung cancer (NSCLC) have increased erlotinib metabolism versus non-smoking patients, which reduces exposure. Therefore, an increased erlotinib dose may be beneficial. The CurrentS study (NCT01183858) assessed efficacy and safety of 300mg erlotinib (E300) as second-line therapy in current smokers with locally advanced or metastatic NSCLC versus the standard 150mg dose (E150). Patients with stage IIIB/IV NSCLC (current smokers who failed first-line platinum-based chemotherapy) were randomized to receive E150 or E300 until progression/death/unacceptable toxicity. progression-free survival (PFS). Secondary endpoints: overall survival (OS), disease control rate and safety. A total of 342 patients were screened; the intent-to-treat population comprised 159 E300 patients and 154 E150 patients. Median PFS was 7.0 versus 6.9 weeks with E300 versus E150, respectively (unstratified hazard ratio [HR]=1.05, 95% confidence interval [CI]: 0.83-1.33; unstratified log-rank P=0.671). Median OS was 6.8 months in both arms (unstratified HR=1.03, 95% CI: 0.80-1.32; unstratified log-rank P=0.846). Overall, 89.2% (E300 arm) and 84.4% (E150 arm) experienced ≥1 adverse event (AE) of any grade (44.3% and 37%, respectively, experienced grade ≥3 AEs); AEs of special interest were reported in 67.7% and 47.4% of patients, respectively. E300 resulted in higher mean plasma concentrations versus E150, however, this did not improve efficacy. Despite the difference in erlotinib exposure, there was no evidence of an incremental efficacy benefit of a higher erlotinib dose versus the standard dose in this population of highly active smokers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Tensile properties of quadruple melted Zr-2.5Nb pressure tubes evaluated from pressure tube offcuts

    International Nuclear Information System (INIS)

    Shah, Priti Kotak; Dubey, J.S.; Anantharaman, S.

    2013-12-01

    Rajasthan Atomic Power Station-2 (RAPS-2) is the first Pressurised Heavy Water Reactor (PHWR) in India having quadruple melted Zr-2.5Nb pressure tubes. Front-end and back-end off-cuts of sixteen pressure tubes were selected for studying the mechanical properties in axial and transverse directions of the tube. Tension tests were carried out at room temperature and at 300℃ using miniature tensile test specimens. The report presents the experimental details and discusses the base line tensile property data for the quadruple melted pressure tubes of RAPS-2. This data will be useful for the reactor life management. (author)

  9. A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-03-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Keisho Chin,1 Toshiharu Yamaguchi2 1Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo, Japan Background: Triweekly capecitabine plus irinotecan (XELIRI is not completely regarded as a valid substitute for fluorouracil, leucovorin, and irinotecan (FOLFIRI in metastatic colorectal cancer (mCRC because of the potential for greater toxicity. We conducted a phase I/II study to assess the efficacy and safety of biweekly XELIRI plus bevacizumab (BV as second-line chemotherapy for mCRC.Methods: Patients with mCRC who had received prior chemotherapy including oxaliplatin and BV and had a UGT1A1 genotype of wild-type or heterozygous for UGT1A1*6 or *28 were eligible for this study. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous irinotecan on day 1, and BV 5 mg/kg on day 1 every 2 weeks. The phase I study consisted of two steps (irinotecan 150 and 180 mg/m2, and dose-limiting toxicity was assessed during the first treatment cycle. The primary endpoint of the phase II study was progression-free survival (PFS.  Results: The recommended dose of irinotecan was determined to be 180 mg/m2 in the phase I study. Between November 2010 and August 2013, 44 patients were enrolled in phase II. The patients’ characteristics were as follows (N=44: median age, 60 years (range 32–80; male/female, 21/23; and UGT1A1 wild-type/heterozygous, 29/15. The median PFS was 6.8 months (95% confidence interval, 5.3–8.2 months, and the primary endpoint was met. Median overall survival was 18.3 months. The response rate was 22.7%. There was no significant difference in PFS or overall survival according to UGT1A1 status. Grade 3 or higher adverse events were mainly neutropenia in six

  10. The efficacy and safety of Oxaliplatin-Vinorelbine as a second-line chemotherapy combination in patients with platinum-resistant pretreated epithelial ovarian cancer: A retrospective study

    Directory of Open Access Journals (Sweden)

    Fidia Mumtahana

    2014-12-01

    Full Text Available Purpose: The main purpose of this study was to analyze the effects and tolerability of Oxaliplatin-Vinorelbine combination on Platinum-resistant epithelial ovarian carcinoma (EOC patients.Methods: A single centered retrospective study comprising of 34 patients was conducted, and all 34 patients were treated with Vinorelbine 30 mg/m2 on day 1 and 8 along with Oxaliplatin 100 mg/m2 on day 1 of 3 weeks treatment cycle following progressive platinum-resistant EOC. Results: The combination showed an overall response rate (ORR of 18% (95% CI, 4.4 - 31.6 where 2 (6% patients had complete response and 4 (12% patients had partial response. Stable disease was observed in 9 (26% patients and progressive disease in 19 (56% patients. Median diseases free survival, median relapse free survival and median time to progression was 17.05 months, 4.4 months, and 1.25 months, respectively. Hematological toxicities were mild; only 1 (2.9% patient had G3 anemia and major non-hematological toxicities include nausea-vomiting, diarrhea, constipation, hepatotoxicity, fatigueness and alopecia, which are mainly limited to G1-G2 and reversible. Conclusion: The effect of this combination is moderate as a second line treatment of platinum resistant EOC; however, in comparison with other regimens of Vinorelbine and Oxaliplatin, the activity is substandard but the toxicity profile is well tolerable. Further multicenter evaluation is needed for the better understanding of the therapeutic efficacy of the combination.

  11. Nanosecond-timescale spin transfer using individual electrons in a quadruple-quantum-dot device

    Energy Technology Data Exchange (ETDEWEB)

    Baart, T. A.; Jovanovic, N.; Vandersypen, L. M. K. [QuTech and Kavli Institute of Nanoscience, Delft University of Technology, P.O. Box 5046, 2600 GA Delft (Netherlands); Reichl, C.; Wegscheider, W. [Solid State Physics Laboratory, ETH Zürich, 8093 Zürich (Switzerland)

    2016-07-25

    The ability to coherently transport electron-spin states between different sites of gate-defined semiconductor quantum dots is an essential ingredient for a quantum-dot-based quantum computer. Previous shuttles using electrostatic gating were too slow to move an electron within the spin dephasing time across an array. Here, we report a nanosecond-timescale spin transfer of individual electrons across a quadruple-quantum-dot device. Utilizing enhanced relaxation rates at a so-called hot spot, we can upper bound the shuttle time to at most 150 ns. While actual shuttle times are likely shorter, 150 ns is already fast enough to preserve spin coherence in, e.g., silicon based quantum dots. This work therefore realizes an important prerequisite for coherent spin transfer in quantum dot arrays.

  12. Relativistic double-zeta, triple-zeta, and quadruple-zeta basis sets for the lanthanides La–Lu

    NARCIS (Netherlands)

    Dyall, K.G.; Gomes, A.S.P.; Visscher, L.

    2010-01-01

    Relativistic basis sets of double-zeta, triple-zeta, and quadruple-zeta quality have been optimized for the lanthanide elements La-Lu. The basis sets include SCF exponents for the occupied spinors and for the 6p shell, exponents of correlating functions for the valence shells (4f, 5d and 6s) and the

  13. On the rates of type Ia supernovae originating from white dwarf collisions in quadruple star systems

    Science.gov (United States)

    Hamers, Adrian S.

    2018-04-01

    We consider the evolution of stellar hierarchical quadruple systems in the 2+2 (two binaries orbiting each other's barycentre) and 3+1 (triple orbited by a fourth star) configurations. In our simulations, we take into account the effects of secular dynamical evolution, stellar evolution, tidal evolution and encounters with passing stars. We focus on type Ia supernovae (SNe Ia) driven by collisions of carbon-oxygen (CO) white dwarfs (WDs). Such collisions can arise from several channels: (1) collisions due to extremely high eccentricities induced by secular evolution, (2) collisions following a dynamical instability of the system, and (3) collisions driven by semisecular evolution. The systems considered here have initially wide inner orbits, with initial semilatus recti larger than 12 {au}, implying no interaction if the orbits were isolated. However, taking into account dynamical evolution, we find that ≈0.4 (≈0.6) of 2+2 (3+1) systems interact. In particular, Roche Lobe overflow can be triggered possibly in highly eccentric orbits, dynamical instability can ensue due to mass-loss-driven orbital expansion or secular evolution, or a semisecular regime can be entered. We compute the delay-time distributions (DTDs) of collision-induced SNe Ia, and find that they are flatter compared to the observed DTD. Moreover, our combined SNe Ia rates are (3.7± 0.7) × 10^{-6} M_⊙^{-1} and (1.3± 0.2) × 10^{-6} M_⊙^{-1} for 2+2 and 3+1 systems, respectively, three orders of magnitude lower compared to the observed rate, of order 10^{-3} M_⊙^{-1}. The low rates can be ascribed to interactions before the stars evolve to CO WDs. However, our results are lower limits given that we considered a subset of quadruple systems.

  14. THE QUADRUPLE PRE-MAIN-SEQUENCE SYSTEM LkCa 3: IMPLICATIONS FOR STELLAR EVOLUTION MODELS

    International Nuclear Information System (INIS)

    Torres, Guillermo; Latham, David W.; Ruíz-Rodríguez, Dary; Prato, L.; Wasserman, Lawrence H.; Badenas, Mariona; Schaefer, G. H.; Mathieu, Robert D.

    2013-01-01

    We report the discovery that the pre-main-sequence (PMS) object LkCa 3 in the Taurus-Auriga star-forming region is a hierarchical quadruple system of M stars. It was previously known to be a close (∼0.''5) visual pair, with one component being a moderately eccentric 12.94 day single-lined spectroscopic binary. A re-analysis of archival optical spectra complemented by new near-infrared (NIR) spectroscopy shows both visual components to be double lined; the second one has a period of 4.06 days and a circular orbit. In addition to the orbital elements, we determine optical and NIR flux ratios, effective temperatures, and projected rotational velocities for all four stars. Using existing photometric monitoring observations of the system that had previously revealed the rotational period of the primary in the longer-period binary, we also detect the rotational signal of the primary in the 4.06 day binary, which is synchronized with the orbital motion. With only the assumption of coevality, a comparison of all of these constraints with current stellar evolution models from the Dartmouth series points to an age of 1.4 Myr and a distance of 133 pc, consistent with previous estimates for the region and suggesting that the system is on the near side of the Taurus complex. Similar comparisons of the properties of LkCa 3 and the well-known quadruple PMS system GG Tau with the widely used models from the Lyon series for a mixing length parameter of α ML = 1.0 strongly favor the Dartmouth models

  15. BD -22 5866: A Low-Mass, Quadruple-lined Spectroscopic and Eclipsing Binary

    Science.gov (United States)

    Shkolnik, Evgenya; Liu, Michael C.; Reid, I. Neill; Hebb, Leslie; Cameron, Andrew C.; Torres, Carlos A.; Wilson, David M.

    2008-08-01

    We report our discovery of an extremely rare, low-mass, quadruple-lined spectroscopic binary BD -22 5866 (=NLTT 53279, integrated spectral type = M0 V), found during an ongoing search for the youngest M dwarfs in the solar neighborhood. From the cross-correlation function, we are able to measure relative flux levels, estimate the spectral types of the components, and set upper limits on the orbital periods and separations. The resulting system is hierarchical, composed of a K7 + K7 binary and an M1 + M2 binary with semimajor axes of aAsin iA system was unresolved with published adaptive optics imaging, limits the projected physical separation of the two binaries at the time of the observation to dABlesssim 4.1 AU at the photometric distance of 51 pc. The maximum observed radial velocity difference between the A and B binaries limits the orbit to aABsin iAB systems, we speculate that an early dynamical process reduced the size of the system, such as the interaction of the two binaries with a circumquadruple disk. Intensive photometric, spectroscopic, and interferometric monitoring, as well as a parallax measurement of this rare quadruple system, is certainly warranted. Based on observations collected at the W. M. Keck Observatory and the Canada-France-Hawaii Telescope (CFHT). The Keck Observatory is operated as a scientific partnership between the California Institute of Technology, the University of California, and NASA, and was made possible by the generous financial support of the W. M. Keck Foundation. The CFHT is operated by the National Research Council of Canada, the Centre National de la Recherche Scientifique of France, and the University of Hawaii.

  16. Democracy and environment as references for quadruple and quintuple helix innovation systems

    Science.gov (United States)

    Carayannis, Elias G.; Campbell, David F. J.; Orr, Barron J.

    2015-04-01

    The perspective of democracy and the ecological context define key references for knowledge production and innovation in innovation systems. Particularly under conditions of environmental change where enhancing the potential for adaptation is critical, this requires a closer look at ecological responsibility and sensitivity in the different innovation models and governance regimes. The "Quintuple Helix" innovation model is an approach that stresses the necessary socio-ecological transition of society and economy by adding an environment helix to an innovation system already made up of three (university-industry-government) or four (civil society relations) helices in a way that supports adaptation by incorporating global warming as both a challenge to and a driver of innovation. There is the proposition that knowledge production and innovation co-evolve with democracy (Carayannis and Campbell, 2014). In the Triple Helix model (Etzkowitz and Leydesdorff, 2000) the existence of a democracy does not appear to be necessary for knowledge production and innovation. However, the Quadruple Helix (Carayannis and Campbell, 2009, 2010 and 2014) is defined and represented by additional key attributes and components: "media-based and culture-based public", "civil society" and "arts, artistic research and arts-based innovation" (Bast, Carayannis and Campbell, 2015). Implications of this are that the fourth helix in the Quadruple Helix innovation systems brings in and represents the perspective of "dimension of democracy" or the "context of democracy" for knowledge in general and knowledge production and innovation in more particular. Within theories of democracy there is a competition between narrow and broader concepts of democracy (Campbell, 2013). This is particularly true when democracy is to be understood to transcend more substantially the narrow understanding of being primarily based on or being primarily rooted in government institutions (within a Triple Helix

  17. Quadruple-layered perovskite (CuCl)Ca2NaNb4O13

    International Nuclear Information System (INIS)

    Kitada, A.; Tsujimoto, Y.; Yamamoto, T.; Kobayashi, Y.; Narumi, Y.; Kindo, K.; Aczel, A.A.; Luke, G.M.; Uemura, Y.J.; Kiuchi, Y.; Ueda, Y.; Yoshimura, K.; Ajiro, Y.; Kageyama, H.

    2012-01-01

    We will present the synthesis, structure and magnetic properties of a new quadruple-layered perovskite (CuCl)Ca 2 NaNb 4 O 13 . Through a topotactic ion-exchange reaction with CuCl 2 , the precursor RbCa 2 NaNb 4 O 13 presumably having an incoherent octahederal tliting changes into (CuCl)Ca 2 NaNb 4 O 13 with a 2a p ×2a p ×2c p superstructure (tetragonal; a=7.73232(5) Å, c=39.2156(4) Å). The well-defined superstructure for the ion-exchanged product should be stabilized by the inserted CuCl 4 O 2 octahedral layers that firmly connect with neighboring perovskite layers. Magnetic studies show the absence of long-range magnetic ordering down to 2 K despite strong in-plane interactions. Aleksandrov′s group theory and Rietveld refinement of synchrotron X-ray diffraction data suggest the structure to be of I4/mmm space group with in-phase tilting along the a and b axes, a two-tilt system (++0). - Graphical Abstract: We present a quadruple-layered copper oxyhalide (CuCl)Ca 2 NaNb 4 O 13 synthesized through a topotactic ion-exchange reaction of RbCa 2 NaNb 4 O 13 with CuCl 2 . The compound has a well-defined superstructure. Magnetic studies suggest the absence of magnetic order even at 2 K. Highlights: ► (CuCl)Ca 2 NaNb 4 O 13 was prepared by ion-exchange reaction of RbCa 2 NaNb 4 O 13 with CuCl 2 . ► Compound has a 2a p ×2a p ×2c p superstructure (tetragonal; a=7.73 Å, c=39.21 Å). ► Such a well-defined superstructure was not observed in the precursor compound. ► Aleksandrov′s theory and Rietveld study suggest a (++0) octahedral tilting (I4/mmm). ► Magnetic studies revealed the absence of magnetic order down to 2 K.

  18. Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs.

    Science.gov (United States)

    Kim, Geon A; Lee, Eun Mi; Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Hwang, Jong Ik; Alam, Zahid; Ahn, Curie; Lee, Byeong Chun

    2017-08-01

    As an alternative source of organs for transplantation into humans, attention has been directed to pigs due to their similarities in biological features and organ size. However, severe immune rejection has prevented successful xenotransplantation using pig organs and tissues. To overcome immune rejection, recently developed genetic engineering systems such as TALEN coupled with somatic cell nuclear transfer (SCNT) to make embryos could be used to produce pigs compatible with xenotransplantation. We used the TALEN system to target the non-Gal antigen cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene in pigs that is naturally deleted in humans. Gal-deleted cells expressing both soluble human tumor necrosis factor receptor I IgG 1 -Fc (shTNFRI-Fc) and human hemagglutinin -tagged-human heme oxygenase-1 (hHO-1) were transfected with a TALEN target for CMAH. Cells lacking CMAH were negatively selected using N-glyconeuraminic acid (Neu5Gc)/magnetic beads and the level of Neu5Gc expression of isolated cells were analyzed by FACS and DNA sequencing. Cloned embryos using 3 different genetically modified cell clones were respectively transferred into 3 recipients, with 55.6% (5/9) becoming pregnant and three cloned pigs were produced. Successful genetic disruption of the CMAH gene was confirmed by sequencing, showing lack of expression of CMAH in tail-derived fibroblasts of the cloned piglets. Besides decreased expression of Neu5Gc in piglets produced by SCNT, antibody-mediated complement-dependent cytotoxicity assays and natural antibody binding for examining immuno-reactivity of the quadruple gene modified pigs derived from endothelial cells and fibroblasts were reduced significantly compared to those of wild type animals. We conclude that by combining the TALEN system and transgenic cells, targeting of multiple genes could be useful for generating organs for xenotransplantation. We produced miniature pigs with quadruple modified genes CMAHKO

  19. Design and reliability, availability, maintainability, and safety analysis of a high availability quadruple vital computer system

    Institute of Scientific and Technical Information of China (English)

    Ping TAN; Wei-ting HE; Jia LIN; Hong-ming ZHAO; Jian CHU

    2011-01-01

    With the development of high-speed railways in China,more than 2000 high-speed trains will be put into use.Safety and efficiency of railway transportation is increasingly important.We have designed a high availability quadruple vital computer (HAQVC) system based on the analysis of the architecture of the traditional double 2-out-of-2 system and 2-out-of-3 system.The HAQVC system is a system with high availability and safety,with prominent characteristics such as fire-new internal architecture,high efficiency,reliable data interaction mechanism,and operation state change mechanism.The hardware of the vital CPU is based on ARM7 with the real-time embedded safe operation system (ES-OS).The Markov modeling method is designed to evaluate the reliability,availability,maintainability,and safety (RAMS) of the system.In this paper,we demonstrate that the HAQVC system is more reliable than the all voting triple modular redundancy (AVTMR) system and double 2-out-of-2 system.Thus,the design can be used for a specific application system,such as an airplane or high-speed railway system.

  20. A quadruple-scanning-probe force microscope for electrical property measurements of microscopic materials

    International Nuclear Information System (INIS)

    Higuchi, Seiji; Kubo, Osamu; Kuramochi, Hiromi; Aono, Masakazu; Nakayama, Tomonobu

    2011-01-01

    Four-terminal electrical measurement is realized on a microscopic structure in air, without a lithographic process, using a home-built quadruple-scanning-probe force microscope (QSPFM). The QSPFM has four probes whose positions are individually controlled by obtaining images of a sample in the manner of atomic force microscopy (AFM), and uses the probes as contacting electrodes for electrical measurements. A specially arranged tuning fork probe (TFP) is used as a self-detection force sensor to operate each probe in a frequency modulation AFM mode, resulting in simultaneous imaging of the same microscopic feature on an insulator using the four TFPs. Four-terminal electrical measurement is then demonstrated in air by placing each probe electrode in contact with a graphene flake exfoliated on a silicon dioxide film, and the sheet resistance of the flake is measured by the van der Pauw method. The present work shows that the QSPFM has the potential to measure the intrinsic electrical properties of a wide range of microscopic materials in situ without electrode fabrication.

  1. Quadruple labelled dual oxygen and pH-sensitive ratiometric nanosensors

    Directory of Open Access Journals (Sweden)

    Veeren M. Chauhan

    2016-05-01

    Full Text Available Nanosensors capable of simultaneously measuring dissolved oxygen concentrations from 0 to 100% saturation and pH over the full physiological range, from pH 3.5 to 7.5, that advance the methods towards understanding of key biological gradients, were synthesised. A library of water soluble oxygen-sensitive porphyrins, with three substituted charged functional groups and a chemically flexible carboxylate functional group were spectroscopically analysed to assess their sensitivity to changes in dissolved oxygen concentrations as free species in solution and in suspension as nanoparticle conjugates. A platinum cationic porphyrin was taken forward to fabricate ratiometric oxygen-sensitive nanosensors, using 5-(and-6-carboxytetramethylrhodamine (TAMRA as internal standard. In addition, quadruple labelled dual oxygen and pH-sensitive nanosensors were synthesised using the cationic Pt porphyrin, pH-sensitive fluorescein dyes, carboxyfluorescein (FAM and Oregon Green (OG, in a 1:1 ratio, and TAMRA. We envisage the dual oxygen and pH nanosensors will find broad utility in the characterisation of diverse microenvironments, where there are complex interactions between molecular oxygen and pH. Keywords: Fluorescent, Phosphorescent, Nanosensor, Oxygen, pH, Ratiometric, Platinum metalloporphyrin

  2. The quadruple bottom line: the advantages of incorporating Green Chemistry into the undergraduate chemistry major

    Science.gov (United States)

    Bodner, George M.

    2017-08-01

    When the author first became involved with the Green Chemistry movement, he noted that his colleagues in industry who were involved in one of the ACS Green Chemistry Institute® industrial roundtables emphasized the take-home message they described as the "triple bottom line." They noted that introducing Green Chemistry in industrial settings had economic, social, and environmental benefits. As someone who first went to school at age 5, and has been "going to school" most days for 65 years, it was easy for the author to see why introducing Green Chemistry into academics had similar beneficial effects within the context of economic, social and environmental domains at the college/university level. He was prepared to understand why faculty who had taught traditional courses often saw the advantage of incorporating Green Chemistry into the courses they teach. What was not as obvious is why students who were encountering chemistry for the first time were often equally passionate about the Green Chemistry movement. Recent attention has been paid, however, to a model that brings clarity to the hitherto vague term of "relevance" that might explain why integrating Green Chemistry into the undergraduate chemistry classroom can achieve a "quadruple bottom-line" for students because of potentially positive effects of adding a domain of "relevance" to the existing economic, social, and environmental domains.

  3. Measurement and analysis of quadruple (αγγ) angular correlations for high spin states of 24Mg

    International Nuclear Information System (INIS)

    Wiedenhoever, I.; Wuosmaa, A. H.; Lister, C. J.; Carpenter, M. P.; Janssens, R. V. F.; Amro, H.; Caggiano, J.; Heinz, A.; Kondev, F. G.; Lauritsen, T.; Siem, S.; Sonzogni, A.; Bhattacharyya, P.; Devlin, M.; Sarantites, D. G.; Sobotka, L. G.

    2000-01-01

    The high-lying, α-decaying states in 24 Mg have been studied by measuring the complete decay path of α and γ emissions using five segmented Silicon detectors in conjunction with GAMMASPHERE. The authors analyzed the (αγ) triple angular correlations and, for the first time, (αγγ) quadruple correlations. The data analysis is based on a new Fourier transformation technique. The power of the technique is demonstrated

  4. Assessment of the accuracy of coupled cluster perturbation theory for open-shell systems. II. Quadruples expansions.

    Science.gov (United States)

    Eriksen, Janus J; Matthews, Devin A; Jørgensen, Poul; Gauss, Jürgen

    2016-05-21

    We extend our assessment of the potential of perturbative coupled cluster (CC) expansions for a test set of open-shell atoms and organic radicals to the description of quadruple excitations. Namely, the second- through sixth-order models of the recently proposed CCSDT(Q-n) quadruples series [J. J. Eriksen et al., J. Chem. Phys. 140, 064108 (2014)] are compared to the prominent CCSDT(Q) and ΛCCSDT(Q) models. From a comparison of the models in terms of their recovery of total CC singles, doubles, triples, and quadruples (CCSDTQ) energies, we find that the performance of the CCSDT(Q-n) models is independent of the reference used (unrestricted or restricted (open-shell) Hartree-Fock), in contrast to the CCSDT(Q) and ΛCCSDT(Q) models, for which the accuracy is strongly dependent on the spin of the molecular ground state. By further comparing the ability of the models to recover relative CCSDTQ total atomization energies, the discrepancy between them is found to be even more pronounced, stressing how a balanced description of both closed- and open-shell species-as found in the CCSDT(Q-n) models-is indeed of paramount importance if any perturbative CC model is to be of chemical relevance for high-accuracy applications. In particular, the third-order CCSDT(Q-3) model is found to offer an encouraging alternative to the existing choices of quadruples models used in modern computational thermochemistry, since the model is still only of moderate cost, albeit markedly more costly than, e.g., the CCSDT(Q) and ΛCCSDT(Q) models.

  5. Investigation of Susceptibility of Mycobacterium tuberculosis Complex Strains Isolated from Clinical Samples Against the First and Second-Line Anti-tuberculosis Drugs by the Sensititre MycoTB Plate Method

    Directory of Open Access Journals (Sweden)

    Figen KAYSERİLİ ORHAN

    2018-03-01

    Full Text Available Introduction: Phenotypic methods for drug susceptibility testing of Mycobacterium tuberculosis complex (MTC to second-line drugs are not yet standardized. The Sensititre MycoTB Plate is a microtiter plate containing lyophilized antibiotics and configured for determination of MIC to first and second-line anti-tuberculosis drugs. The purpose of this study is to detect the susceptibility rates of MTC strains isolated from patients’ specimens for first and second-line anti-tuberculosis drugs. Materials and Methods: This study included 50 MTC strains isolated from various clinical specimens. Out of the 50 strains, 38 were isolated from sputum, three from cerebrospinal fluid, three from bronchoalveolar lavage, and six from other samples in this study. The susceptibility of strains to anti-tuberculosis drugs were determined by the Sensititre MycoTB Plate Method. Thawed isolates were subcultured, and dilutions were inoculated into MycoTB wells. The results were read at days 7, 14 and 21. Results: At the end of study, out of 50 MTC isolates, 7 (14% showed resistance to Isoniazid (INH, 5 (10% to streptomycin (SM, 4 (8% to ethambutol (EMB, 4 (8% to ethionamide (ETH, 3 (6% to rifampicin (RIF, 3 (6% to rifabutin (RFB, 2 (4% to kanamycin (KAN, 2 (4% to ofloxacin (OFL, 2 (4% to P-aminosalicyclic acid (PAS, 1 (2% to moxiflocacin (MOX, and 1 (2% to cycloserine (CYC. All strains were found sensitive to amikacin while 2 strains (4% were identified as multidrug-resistant tuberculosis (MDR-TB. Thirty-five strains (70% were sensitive to all drugs. Extensively drug resistant tuberculosis (XDR-TB was not determined in this study. Conclusion: This is the first study that tests second line anti-tuberculosis drugs in our location and provides us valuable data regarding MDR-TB and XDR-TB rates. The Sensititre MycoTB Plate Method is a fast, reliable and practical method and can be used to determine the susceptibility of first and second-line anti-tuberculosis drugs.

  6. The Efficacy of Sequential Therapy in Eradication of Helicobacter ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... pylori (H. pylori) eradication rates of standard triple, sequential and quadruple therapies including claritromycin regimes in this study. Materials and Methods: A total of 160 patients with dyspeptic symptoms were enrolled to the study. The patients were randomized to four groups of treatment protocols.

  7. The efficacy of sequential therapy in eradication of Helicobacter ...

    African Journals Online (AJOL)

    ... the Helicobacter pylori (H. pylori) eradication rates of standard triple, sequential and quadruple therapies including claritromycin regimes in this study. Materials and Methods: A total of 160 patients with dyspeptic symptoms were enrolled to the study. The patients were randomized to four groups of treatment protocols.

  8. Line roughness improvements on self-aligned quadruple patterning by wafer stress engineering

    Science.gov (United States)

    Liu, Eric; Ko, Akiteru; Biolsi, Peter; Chae, Soo Doo; Hsieh, Chia-Yun; Kagaya, Munehito; Lee, Choongman; Moriya, Tsuyoshi; Tsujikawa, Shimpei; Suzuki, Yusuke; Okubo, Kazuya; Imai, Kiyotaka

    2018-04-01

    In integrated circuit and memory devices, size shrinkage has been the most effective method to reduce production cost and enable the steady increment of the number of transistors per unit area over the past few decades. In order to reduce the die size and feature size, it is necessary to minimize pattern formation in the advance node development. In the node of sub-10nm, extreme ultra violet lithography (EUV) and multi-patterning solutions based on 193nm immersionlithography are the two most common options to achieve the size requirement. In such small features of line and space pattern, line width roughness (LWR) and line edge roughness (LER) contribute significant amount of process variation that impacts both physical and electrical performances. In this paper, we focus on optimizing the line roughness performance by using wafer stress engineering on 30nm pitch line and space pattern. This pattern is generated by a self-aligned quadruple patterning (SAQP) technique for the potential application of fin formation. Our investigation starts by comparing film materials and stress levels in various processing steps and material selection on SAQP integration scheme. From the cross-matrix comparison, we are able to determine the best stack of film selection and stress combination in order to achieve the lowest line roughness performance while obtaining pattern validity after fin etch. This stack is also used to study the step-by-step line roughness performance from SAQP to fin etch. Finally, we will show a successful patterning of 30nm pitch line and space pattern SAQP scheme with 1nm line roughness performance.

  9. Transportal anterior cruciate ligament reconstruction with quadrupled hamstring tendon graft: A prospective outcome study

    Directory of Open Access Journals (Sweden)

    Chandan Kumar

    2017-01-01

    Full Text Available Background: Anterior cruciate ligament (ACL reconstruction has been one of the most commonly performed procedures throughout the world. Unsatisfactory outcome with conventional ACL reconstruction has been attributed to nonanatomic graft placement. Researchers have advised placing the graft in the native footprint of ACL to avoid nonanatomic graft placement. The goal of this study was to analyze the outcome of anatomic single bundle ACL reconstruction using transportal technique. Materials and Methods: This was a prospective outcome study conducted on 85 consecutive patients of ACL reconstruction of which 62 patients met inclusion and exclusion criteria and were analyzed for final results. All the patients underwent ACL reconstruction by quadrupled hamstring tendon graft using transportal technique and the accessory anteromedial (AAM portal for femoral tunnel creation. The graft was fixed with endobutton on femoral side and bioabsorbable screw on the tibial side. Patients were evaluated for range of motion, International Knee Documentation Committee (IKDC score, and Lysholm scores at a minimum followup period of 2 years. The mean pre- and postoperative scores were compared using Wilcoxon signed-rank test. Results: The mean Lysholm and IKDC scores improved significantly (P < 0.0001 from preoperative value. According to IKDC score, 90.3% (n = 56 were either normal or near normal at final followup. According to Lysholm score, 75.8% of patients had excellent and 13.3% had good results. Preoperatively, pivot shift was present in 85.5% (n = 53 of patients which reduced to 4.8% (n = 3 postoperatively. Infection and knee stiffness occurred in two patients, and femoral tunnel blowout and graft re-rupture occurred in one patient each. Conclusion: Anatomic ACL reconstruction by AAM portal is a reproducible technique which gives good clinical outcome at short-term followup.

  10. Design of dual band FSS by using quadruple L-slot technique

    Science.gov (United States)

    Fauzi, Noor Azamiah Md; Aziz, Mohamad Zoinol Abidin Abd.; Said, Maizatul Alice Meor; Othman, Mohd Azlishah; Ahmad, Badrul Hisham; Malek, Mohd Fareq Abd

    2015-05-01

    This paper presents a new design of dual band frequency selective surface (FSS) for band pass microwave transmission application. FSS can be used on energy saving glass to improve the transmission of wireless communication signals through the glass. The microwave signal will be attenuate when propagate throughout the different structure such as building. Therefore, some of the wireless communication system cannot be used in the optimum performance. The aim of this paper is designed, simulated and analyzed the new dual band FSS structure for microwave transmission. This design is based on a quadruple L slot combined with cross slot to produce pass band at 900 MHz and 2.4 GHz. The vertical of pair inverse L slot is used as the band pass for the frequency of 2.4GHz. While, the horizontal of pair inverse L slot is used as the band pass at frequency 900MHz. This design is simulated and analyzed by using Computer Simulation Technology (CST) Microwave Studio (MWS) software. The characteristics of the transmission (S21) and reflection (S11) of the dual band FSS were simulater and analyzed. The bandwidth of the first band is 118.91MHz which covered the frequency range from 833.4MHz until 952.31MHz. Meanwhile, the bandwidth for the second band is 358.84MHz which covered the frequency range from 2.1475GHz until 2.5063GHz. The resonance/center frequency of this design is obtained at 900MHz with a 26.902dB return loss and 2.37GHz with 28.506dB a return loss. This FSS is suitable as microwave filter for GSM900 and WLAN 2.4GHz application.

  11. Everolimus plus exemestane versus bevacizumab-based chemotherapy for second-line treatment of hormone receptor-positive metastatic breast cancer in Greece: An economic evaluation study.

    Science.gov (United States)

    Kourlaba, Georgia; Rapti, Vasiliki; Alexopoulos, Athanasios; Relakis, John; Koumakis, Georgios; Chatzikou, Magdalini; Maniadakis, Nikos; Georgoulias, Vassilis

    2015-08-05

    The objective of our study was to conduct a cost-effectiveness (CE) study of combined everolimus (EVE) and exemestane (EXE) versus the common clinical practice in Greece for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer (BC) progressing on nonsteroidal aromatase inhibitors (NSAI). The combinations of bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) were selected as comparators. A Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of the comparators from a third-party payer perspective over a lifetime horizon. Efficacy and safety data as well as utility values considered in the model were extracted from the relevant randomized Phase III clinical trials and other published studies. Direct medical costs referring to the year 2014 were incorporated in the model. A probabilistic sensitivity analysis was conducted to account for uncertainty and variation in the parameters of the model. Primary outcomes were patient survival (life-years), quality-adjusted life years (QALYs), total direct costs and incremental cost-effectiveness ratios (ICER). The discounted quality-adjusted survival of patients treated with EVE plus EXE was greater by 0.035 and 0.004 QALYs, compared to BEV plus PACL and BEV plus CAPE, respectively. EVE plus EXE was the least costly treatment in terms of drug acquisition, administration, and concomitant medications. The total lifetime cost per patient was estimated at €55,022, €67,980, and €62,822 for EVE plus EXE, BEV plus PACL, and BEV plus CAPE, respectively. The probabilistic analysis confirmed the deterministic results. Our results suggest that EVE plus EXE may be a dominant alternative relative to BEV plus PACL and BEV plus CAPE for the treatment of HR+/HER2- advanced BC patients failing initial therapy with NSAIs.

  12. HH 222: A GIANT HERBIG-HARO FLOW FROM THE QUADRUPLE SYSTEM V380 ORI

    Energy Technology Data Exchange (ETDEWEB)

    Reipurth, Bo; Aspin, Colin; Connelley, M. S. [Institute for Astronomy, University of Hawaii at Manoa, 640 North Aohoku Place, Hilo, HI 96720 (United States); Bally, John [Center for Astrophysics and Space Astronomy, University of Colorado, Boulder, CO 80309 (United States); Geballe, T. R. [Gemini Observatory, 670 North Aohoku Place, Hilo, HI 96720 (United States); Kraus, Stefan [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, MS-78, Cambridge, MA 02138 (United States); Appenzeller, Immo [Landessternwarte Heidelberg, Königstuhl 12, D-69117 Heidelberg (Germany); Burgasser, Adam, E-mail: reipurth@ifa.hawaii.edu, E-mail: caa@ifa.hawaii.edu, E-mail: msc@ifa.hawaii.edu, E-mail: John.Bally@colorado.edu, E-mail: tgeballe@gemini.edu, E-mail: stefan.kraus@cfa.harvard.edu, E-mail: iappenze@lsw.uni-heidelberg.de, E-mail: aburgasser@ucsd.edu [Center for Astrophysics and Space Science, University of California San Diego, La Jolla, CA 92093 (United States)

    2013-11-01

    HH 222 is a giant shocked region in the L1641 cloud, and is popularly known as the Orion Streamers or ''the waterfall'' on account of its unusual structure. At the center of these streamers are two infrared sources coincident with a nonthermal radio jet aligned along the principal streamer. The unique morphology of HH 222 has long been associated with this radio jet. However, new infrared images show that the two sources are distant elliptical galaxies, indicating that the radio jet is merely an improbable line-of-sight coincidence. Accurate proper motion measurements of HH 222 reveal that the shock structure is a giant bow shock moving directly away from the well-known, very young, Herbig Be star V380 Ori. The already known Herbig-Haro object HH 35 forms part of this flow. A new Herbig-Haro object, HH 1041, is found precisely in the opposite direction of HH 222 and is likely to form part of a counterflow. The total projected extent of this HH complex is 5.3 pc, making it among the largest HH flows known. A second outflow episode from V380 Ori is identified as a pair of HH objects, HH 1031 to the northwest and the already known HH 130 to the southeast, along an axis that deviates from that of HH 222/HH 1041 by only 3.°7. V380 Ori is a hierarchical quadruple system, including a faint companion of spectral type M5 or M6, which at an age of ∼1 Myr corresponds to an object straddling the stellar-to-brown dwarf boundary. We suggest that the HH 222 giant bow shock is a direct result of the dynamical interactions that led to the conversion from an initial non-hierarchical multiple system into a hierarchical configuration. This event occurred no more than 28,000 yr ago, as derived from the proper motions of the HH 222 giant bow shock.

  13. Linear discrete-time state space realization of a modified quadruple tank system with state estimation using Kalman filter

    DEFF Research Database (Denmark)

    Mohd. Azam, Sazuan Nazrah

    2017-01-01

    In this paper, we used the modified quadruple tank system that represents a multi-input-multi-output (MIMO) system as an example to present the realization of a linear discrete-time state space model and to obtain the state estimation using Kalman filter in a methodical mannered. First, an existing...... part of the Kalman filter is used to estimates the current state, based on the model and the measurements. The static and dynamic Kalman filter is compared and all results is demonstrated through simulations....

  14. SELDI-TOF MS of quadruplicate urine and serum samples to evaluate changes related to storage conditions.

    Science.gov (United States)

    Traum, Avram Z; Wells, Meghan P; Aivado, Manuel; Libermann, Towia A; Ramoni, Marco F; Schachter, Asher D

    2006-03-01

    Proteomic profiling with SELDI-TOF MS has facilitated the discovery of disease-specific protein profiles. However, multicenter studies are often hindered by the logistics required for prompt deep-freezing of samples in liquid nitrogen or dry ice within the clinic setting prior to shipping. We report high concordance between MS profiles within sets of quadruplicate split urine and serum samples deep-frozen at 0, 2, 6, and 24 h after sample collection. Gage R&R results confirm that deep-freezing times are not a statistically significant source of SELDI-TOF MS variability for either blood or urine.

  15. Mechanisms of antibiotic resistance in Mycobacterium tuberculosis, validation of methods BACTECTM MGIT 960 and AnyplexM TII MTB / MDR / XDR Detection for detection of antibiotic resistance to first and second line in Mycobacterium tuberculosis strains

    International Nuclear Information System (INIS)

    Centeno Urena, Yadel

    2014-01-01

    A literature review is developed of drug-resistant TB in the world and in Costa Rica. The mechanisms of resistance to antibiotics are studied of the bacterium that causes tuberculosis; drug resistance to first-line and second-line, treatment regimen according to the World Health Organization and edge detection methods available in the market. The agreement between the results is studied by the phenotypic detection system of resistance of M. tuberculosis BACTEC MGIT960 and PCR, in real-time of commercial kit Anyplex II MTB/MDR/XDR, for genotypic identification of M. tuberculosis and related mutations to resistance with the referring results to thirty strains provided by the Pan American Health Organization, allowing a significant shortening in the time of obtaining reliable results. The results obtained have allowed to suggest a possible implementation at the Centro Nacional de Referencia en Micobacteriologia (CNRM), to perform antibiotic susceptibility testing and genotypic testing of multidrug cases respectively. The study results have allowed the implementation of the technology of genotypic detection of M. tuberculosis in the CNRM, obtaining for the first time in Costa Rica, information about genes of M. tuberculosis related to the generation of resistance to the major drugs of Primary treatment scheme as well as testing of resistance to second-line drug for resistant strains referred to the Centro Nacional de Referencia en Micobacteriologia in 2013. (author) [es

  16. ENDOSCOPIC DIAGNOSIS AND THERAPY IN GASTRO-ESOPAGEAL VARICEAL BLEEDING

    Science.gov (United States)

    Sanyal, Arun J.

    2016-01-01

    Gastroesophageal variceal hemorrhage is a medical emergency with high morbidity and mortality. Endoscopic therapy is the mainstay of management of bleeding varices. It requires attention to technique and the appropriate choice of therapy for a given patient at a given point in time. Subjects must be monitored continuously after initiation of therapy for control of bleeding and second line definitive therapies introduced quickly if endoscopic and pharmacologic treatment fails. PMID:26142034

  17. HE 1113-0641: THE SMALLEST-SEPARATION QUADRUPLE LENS IDENTIFIED BY A GROUND-BASED OPTICAL TELESCOPE

    International Nuclear Information System (INIS)

    Blackburne, Jeffrey A.; Schechter, Paul L.; Wisotzki, Lutz

    2008-01-01

    The Hamburg/ESO quasar HE 1113-0641 is found to be a quadruple gravitational lens, based on observations with the twin 6.5 m Magellan telescopes at the Las Campanas Observatory, and subsequently with the Hubble Space Telescope. The z S = 1.235 quasar appears in a cross configuration, with i' band magnitudes ranging from 18.0 to 18.8. With a maximum image separation of 0''.67, this is the smallest-separation quadruple ever identified using a ground-based optical telescope. Point-spread function (PSF) subtraction reveals a faint lensing galaxy. A simple lens model succeeds in predicting the observed positions of the components, but fails to match their observed flux ratios by up to a magnitude. We estimate the redshift of the lensing galaxy to be z L ∼ 0.7. Time delay estimates are on the order of a day, suggesting that the flux ratio anomalies are not due to variability of the quasar, but may result from substructure or microlensing in the lens galaxy.

  18. Epi-detected quadruple-modal nonlinear optical microscopy for label-free imaging of the tooth

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zi; Zheng, Wei; Huang, Zhiwei, E-mail: biehzw@nus.edu.sg [Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117576 (Singapore); Stephen Hsu, Chin-Ying [Department of Dentistry, Faculty of Dentistry, National University of Singapore and National University Health System, Singapore 119083 (Singapore)

    2015-01-19

    We present an epi-detected quadruple-modal nonlinear optical microscopic imaging technique (i.e., coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), third-harmonic generation (THG), and two-photon excited fluorescence (TPEF)) based on a picosecond (ps) laser-pumped optical parametric oscillator system for label-free imaging of the tooth. We demonstrate that high contrast ps-CARS images covering both the fingerprint (500–1800 cm{sup −1}) and high-wavenumber (2500–3800 cm{sup −1}) regions can be acquired to uncover the distributions of mineral and organic biomaterials in the tooth, while high quality TPEF, SHG, and THG images of the tooth can also be acquired under ps laser excitation without damaging the samples. The quadruple-modal nonlinear microscopic images (CARS/SHG/THG/TPEF) acquired provide better understanding of morphological structures and biochemical/biomolecular distributions in the dentin, enamel, and the dentin-enamel junction of the tooth without labeling, facilitating optical diagnosis and characterization of the tooth in dentistry.

  19. Light and Electrically Induced Phase Segregation and Its Impact on the Stability of Quadruple Cation High Bandgap Perovskite Solar Cells.

    Science.gov (United States)

    Duong, The; Mulmudi, Hemant Kumar; Wu, YiLiang; Fu, Xiao; Shen, Heping; Peng, Jun; Wu, Nandi; Nguyen, Hieu T; Macdonald, Daniel; Lockrey, Mark; White, Thomas P; Weber, Klaus; Catchpole, Kylie

    2017-08-16

    Perovskite material with a bandgap of 1.7-1.8 eV is highly desirable for the top cell in a tandem configuration with a lower bandgap bottom cell, such as a silicon cell. This can be achieved by alloying iodide and bromide anions, but light-induced phase-segregation phenomena are often observed in perovskite films of this kind, with implications for solar cell efficiency. Here, we investigate light-induced phase segregation inside quadruple-cation perovskite material in a complete cell structure and find that the magnitude of this phenomenon is dependent on the operating condition of the solar cell. Under short-circuit and even maximum power point conditions, phase segregation is found to be negligible compared to the magnitude of segregation under open-circuit conditions. In accordance with the finding, perovskite cells based on quadruple-cation perovskite with 1.73 eV bandgap retain 94% of the original efficiency after 12 h operation at the maximum power point, while the cell only retains 82% of the original efficiency after 12 h operation at the open-circuit condition. This result highlights the need to have standard methods including light/dark and bias condition for testing the stability of perovskite solar cells. Additionally, phase segregation is observed when the cell was forward biased at 1.2 V in the dark, which indicates that photoexcitation is not required to induce phase segregation.

  20. MODELING THE RADIO EMISSION FROM Cyg OB2 NO. 5: A QUADRUPLE SYSTEM?

    International Nuclear Information System (INIS)

    Kennedy, M.; Dougherty, S. M.; Fink, A.; Williams, P. M.

    2010-01-01

    literature suggests reflex motion of the binary due to Star C, for which a mass of 23 +22 -14 M sun is deduced. The natures of NE and Star D are also examined. If NE is a WCR, as suggested by other authors, then the required mass-loss rate is an order of magnitude higher than expected for an early B-type dwarf, and only just consistent with a supergiant. This raises the question of NE as a WCR, but its non-thermal luminosity is consistent with a WCR and a comparison of reddening between Cyg OB2 No. 5 and Star D do not rule out an association, implying Cyg OB2 No. 5 is a quadruple system. Pursuing alternative models for NE, such as an unassociated background source, would require very challenging observations.

  1. The Gaia-ESO Survey: double-, triple-, and quadruple-line spectroscopic binary candidates

    Science.gov (United States)

    Merle, T.; Van Eck, S.; Jorissen, A.; Van der Swaelmen, M.; Masseron, T.; Zwitter, T.; Hatzidimitriou, D.; Klutsch, A.; Pourbaix, D.; Blomme, R.; Worley, C. C.; Sacco, G.; Lewis, J.; Abia, C.; Traven, G.; Sordo, R.; Bragaglia, A.; Smiljanic, R.; Pancino, E.; Damiani, F.; Hourihane, A.; Gilmore, G.; Randich, S.; Koposov, S.; Casey, A.; Morbidelli, L.; Franciosini, E.; Magrini, L.; Jofre, P.; Costado, M. T.; Jeffries, R. D.; Bergemann, M.; Lanzafame, A. C.; Bayo, A.; Carraro, G.; Flaccomio, E.; Monaco, L.; Zaggia, S.

    2017-12-01

    Context. The Gaia-ESO Survey (GES) is a large spectroscopic survey that provides a unique opportunity to study the distribution of spectroscopic multiple systems among different populations of the Galaxy. Aims: Our aim is to detect binarity/multiplicity for stars targeted by the GES from the analysis of the cross-correlation functions (CCFs) of the GES spectra with spectral templates. Methods: We developed a method based on the computation of the CCF successive derivatives to detect multiple peaks and determine their radial velocities, even when the peaks are strongly blended. The parameters of the detection of extrema (DOE) code have been optimized for each GES GIRAFFE and UVES setup to maximize detection. The DOE code therefore allows to automatically detect multiple line spectroscopic binaries (SBn, n ≥ 2). Results: We apply this method on the fourth GES internal data release and detect 354 SBn candidates (342 SB2, 11 SB3, and even one SB4), including only nine SBs known in the literature. This implies that about 98% of these SBn candidates are new because of their faint visual magnitude that can reach V = 19. Visual inspection of the SBn candidate spectra reveals that the most probable candidates have indeed a composite spectrum. Among the SB2 candidates, an orbital solution could be computed for two previously unknown binaries: CNAME 06404608+0949173 (known as V642 Mon) in NGC 2264 and CNAME 19013257-0027338 in Berkeley 81 (Be 81). A detailed analysis of the unique SB4 (four peaks in the CCF) reveals that CNAME 08414659-5303449 (HD 74438) in the open cluster IC 2391 is a physically bound stellar quadruple system. The SB candidates belonging to stellar clusters are reviewed in detail to discard false detections. We suggest that atmospheric parameters should not be used for these system components; SB-specific pipelines should be used instead. Conclusions: Our implementation of an automatic detection of spectroscopic binaries within the GES has allowed the

  2. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life.

    Science.gov (United States)

    Palumbo, Raffaella; Sottotetti, Federico; Trifirò, Giuseppe; Piazza, Elena; Ferzi, Antonella; Gambaro, Anna; Spinapolice, Elena Giulia; Pozzi, Emma; Tagliaferri, Barbara; Teragni, Cristina; Bernardo, Antonio

    2015-01-01

    A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to

  3. 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.

  4. Second Line of Defense Master Spares Catalog

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Dale L.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.

    2012-11-20

    This catalog is intended to be a comprehensive listing of repair parts, components, kits, and consumable items used on the equipment deployed at SLD sites worldwide. The catalog covers detection, CAS, network, ancillary equipment, and tools. The catalog is backed by a Master Parts Database which is used to generate the standard report views of the catalog. The master parts database is a relational database containing a record for every part in the master parts catalog along with supporting tables for normalizing fields in the records. The database also includes supporting queries, database maintenance forms, and reports.

  5. 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.

  6. Application of CaCu3Ti4O12 based quadruple perovskites as a promising candidate for optoelectronic devices

    Science.gov (United States)

    Pal, Kamalesh; Jana, Rajkumar; Dey, Arka; Ray, Partha P.; Seikh, Md Motin; Gayen, Arup

    2018-05-01

    We report the synthesis of nanosized (40-50 nm) CaCu3-xMnxTi4-xMnxO12 (x = 0, 0.5 and 1) quadruple perovskite (QP) semiconductor via a modified combustion method for use as Schottky barrier diode (SBD) at the Al/QP junction. The fabricated SBD is analysed on the basis of thermionic emission theory to observe its quality and some important diode parameters. For insight analysis of charge transport mechanism through metal-semiconductor junction, theory of space charge limited currents is applied and discussed in the light of parameters like carrier concentration, mobility-lifetime product and diffusion length. The Mn-doped exhibit better device performance compared to parent material.

  7. A quadruple quasar coincident with a giant Ly-alpha nebula and a protocluster at z=2

    Science.gov (United States)

    Vignali, Cristian

    2016-09-01

    We propose to observe the only known quadruple AGN system in the Universe, embedded in a giant Ly-alpha nebula at z 2. These active nuclei and the large number of Ly-alpha emitting galaxies at the same redshift are clear indications that this is one of the most overdense protoclusters known z 2. We request a 140 ks Chandra exposure to (a) define the basic X-ray properties of all the AGN and then their bolometric luminosities and Eddington ratios, and compare these with those of "isolated" quasars at similar redshifts/luminosities; (b) detect the hot gas emission in the protocluster. Chandra is unique for this investigation: the close (few arcsec) distance of some of the AGN needs high spatial resolution, and the extended emission requires low background contribution.

  8. 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...

  9. LHRH analogue as a depot preparation (Zoladex) in the treatment of advanced carcinoma of the prostate followed by orchiectomy as a second line therapy--a phase II study

    DEFF Research Database (Denmark)

    Iversen, P; Rose, C; Stage, J G

    1989-01-01

    in 68% of the patients. During treatment, serum testosterone was in the castrate range in all patients except five. Possible explanations for this escape phenomenon are discussed. No toxicity was observed and treatment was well tolerated in all patients. Thirty-two patients underwent bilateral...

  10. 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 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 the confer...

  11. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1)

    DEFF Research Database (Denmark)

    Machiels, Jean-Pascal H; Haddad, Robert I; Fayette, Jérôme

    2015-01-01

    BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting......%]), and neutropenia (1 [... provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. FUNDING: Boehringer Ingelheim....

  12. An exploratory case study of the impact of expanding cost-effectiveness analysis for second-line nivolumab for patients with squamous non-small cell lung cancer in Canada: Does it make a difference?

    Science.gov (United States)

    Shafrin, Jason; Skornicki, Michelle; Brauer, Michelle; Villeneuve, Julie; Lees, Michael; Hertel, Nadine; Penrod, John R; Jansen, Jeroen

    2018-04-26

    Health technology appraisal agencies often rely on cost-effectiveness analyses to inform coverage decisions for new treatments. These assessments, however, frequently measure a treatment's value from the payer's perspective, and may not capture value generated from reduced caregiving costs, increased productivity, value based on patient risk preferences, option value or the insurance value to non-patients. To examine how using a broader societal perspective of treatment value affects cost-effectiveness estimates, this case study analyzed the net monetary benefit (NMB) of second-line nivolumab treatment of patients with squamous non-small cell lung cancer (NSCLC) in Canada. The comparator was treatment with docetaxel. NMB was measured from three perspectives: (i) traditional payer, (ii) traditional societal and (iii) broad societal. Nivolumab was more effective (increased quality-adjusted life years by 0.66 versus docetaxel), but also increased costs by $100,168 CAD. When valuing a quality-adjusted life year at $150,000, the net monetary benefit from the payer perspective suggested that costs modestly exceed benefits (NMB: -$1031). Adopting a societal perspective, however, nivolumab's benefits outweighed its costs (NMB: +$6752 and +$91,084 from the traditional and broad societal perspectives, respectively). Broadening cost-effectiveness analysis beyond the traditional payer perspective had a significant impact on the result and should be considered in order to capture all treatment benefits and costs of societal relevance. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Using the Quadruple Aim Framework to Measure Impact of Heath Technology Implementation: A Case Study of eConsult.

    Science.gov (United States)

    Liddy, Clare; Keely, Erin

    2018-01-01

    Health technology solutions are too often implemented without a true understanding of the system-level problem they seek to address, resulting in excessive costs, poor adoption, ineffectiveness, and ultimately failure. Before implementing or adopting health care innovations, stakeholders should complete a thorough assessment to ensure effectiveness and value. In this article, we describe how to evaluate the impact of a health technology innovation through the 4 dimensions of care outlined by the Quadruple Aim Framework, using our experience with the Champlain Building Access to Specialists through eConsultation (BASE) eConsult service as a case example. A descriptive overview of data was collected between April 1, 2011, and August 31, 2017, using 4 dimensions of care outlined by the Quadruple Aim Framework: patient experience, provider experience, costs, and population health. Findings were drawn from use data, primary care provider closeout surveys, surveys/interviews with patients and provider, and costing data. Overall, patients have received access to specialist advice within days and find the advice useful in 86% of cases. Provider experience is very positive, with satisfaction ratings of high/very high value in 94% of cases. The service cost a weighted average of $47.35/case, compared with $133.60/case for traditional referrals. In total, 1,299 primary care providers have enrolled in the service, completing 28,838 cases since 2011. Monthly case volumes have grown from an average of 13 cases/month in 2011 to 969 cases/month in 2016. The eConsult service has been widely adopted in our region and is currently expanding to new jurisdictions across Canada. However, although we successfully demonstrated eConsult's impact on patient experience, provider satisfaction, and reducing costs, we met several challenges in evaluating its impact on population health. More work is needed to evaluate eConsult's impact on key population health metrics (eg, mortality, morbidity

  14. Self-Focusing of Quadruple Gaussian Laser Beam in an Inhomogenous Magnetized Plasma with Ponderomotive Non-Linearity: Effect of Linear Absorption

    International Nuclear Information System (INIS)

    Aggarwal, Munish; Vij, Shivani; Kant, Niti

    2015-01-01

    The propagation of quadruple Gaussian laser beam in a plasma characterized by axial inhomogeneity and nonlinearity due to ponderomotive force in the paraxial ray approximation is investigated. An appropriate expression for the nonlinear dielectric constant has been developed in the presence of external magnetic field, with linear absorption and due to saturation effects for arbitrary large intensity. The effects of different types of plasma axial inhomogeneities on self-focusing of laser beam have been studied with the typical laser and plasma parameters. Self-focusing of quadruple Gaussian laser beam in the presence of externally applied magnetic field and saturating parameter is found significantly improved in the case of extraordinary mode. Our results reveal that initially converging beam shows oscillatory convergence whereas initially diverging beam shows oscillatory divergence. The beam is more focussed at lower intensity in both cases viz. extraordinary and ordinary mode. (paper)

  15. Reduction of measurement uncertainty by experimental design in high-order (double, triple, and quadruple) isotope dilution mass spectrometry: application to GC-MS measurement of bromide.

    Science.gov (United States)

    Pagliano, Enea; Mester, Zoltán; Meija, Juris

    2013-03-01

    Since its introduction a century ago, isotope dilution analysis has played a central role in developments of analytical chemistry. This method has witnessed many elaborations and developments over the years. To date, we have single, double, and even triple isotope dilution methods. In this manuscript, we summarize the conceptual aspects of isotope dilution methods and introduce the quadruple dilution and the concept of exact matching triple and quadruple dilutions. The comparison of isotope dilution methods is performed by determination of bromide ions in groundwater using novel ethyl-derivatization chemistry in conjunction with GC/MS. We show that the benefits of higher-order isotope dilution methods are countered with a greater need for careful experimental design of the isotopic blends. Just as for ID(2)MS, ID(3)MS and ID(4)MS perform best when the isotope ratio of one sample/spike blend is matched with that of a standard/spike blend (exact matching).

  16. Flow structure and heat transfer in a square duct fitted with dual/quadruple twisted-tapes: Influence of tape configuration

    International Nuclear Information System (INIS)

    Eiamsa-ard, S.; Changcharoen, W.

    2015-01-01

    Numerical predictions reported of thermohydraulic characteristics of square ducts equipped with dual and quadruple twisted tapes (DTs and QTs) with different configurations. The studied cases include (1) dual co-tapes (Co-DTs), (2) dual counter-tapes (C-DTs), (3) diagonal dual counter-tapes (C-DDTs), (4) diagonal dual co-tapes (Co-DDTs), (5) quadruple co-tapes (Co-QTs), (6) quadruple counter tapes (CC-QTs) and (7) quadruple counter-tapes (PC-QTs). The results of these cases are compared with those of a smooth duct (a duct without tape insert) and also the one with a single tape (ST). The prediction involves using the RNG k-ε turbulent model under constant wall heat flux condition in the turbulent flow regime for the Reynolds number ranging from 6000 to 14000. The prediction indicates that thermohydraulic characteristics in ducts with twisted tape are strongly dependent on number and configuration of tapes. However, the influence of tape number is more significant than that of tape configuration. Heat transfer and friction increase as tape number increases. QTs offer superior heat transfer to DTs but their thermal performance factors are lower. For the tape inserts determined, DTs with diagonal configuration (Co-DDTs and C-DDTs) is the best design as the tapes offer the best thermal performance. The highest thermal performance factors given by Co-DTs, Co-DDTs, C-DTs, C-DDTs, Co-QTs, PC-QTs and CC-QTs, are around 1.21, 1.35, 1.25, 1.38, 1.08, 1.18, and 1.22, respectively

  17. Augmented Quadruple-Phase Contrast Media Administration and Triphasic Scan Protocol Increases Image Quality at Reduced Radiation Dose During Computed Tomography Urography.

    Science.gov (United States)

    Saade, Charbel; Mohamad, May; Kerek, Racha; Hamieh, Nadine; Alsheikh Deeb, Ibrahim; El-Achkar, Bassam; Tamim, Hani; Abdul Razzak, Farah; Haddad, Maurice; Abi-Ghanem, Alain S; El-Merhi, Fadi

    The aim of this article was to investigate the opacification of the renal vasculature and the urogenital system during computed tomography urography by using a quadruple-phase contrast media in a triphasic scan protocol. A total of 200 patients with possible urinary tract abnormalities were equally divided between 2 protocols. Protocol A used the conventional single bolus and quadruple-phase scan protocol (pre, arterial, venous, and delayed), retrospectively. Protocol B included a quadruple-phase contrast media injection with a triphasic scan protocol (pre, arterial and combined venous, and delayed), prospectively. Each protocol used 100 mL contrast and saline at a flow rate of 4.5 mL. Attenuation profiles and contrast-to-noise ratio of the renal arteries, veins, and urogenital tract were measured. Effective radiation dose calculation, data analysis by independent sample t test, receiver operating characteristic, and visual grading characteristic analyses were performed. In arterial circulation, only the inferior interlobular arteries in both protocols showed a statistical significance (P contrast-to-noise ratio than protocol A (protocol B: 22.68 ± 13.72; protocol A: 14.75 ± 5.76; P contrast media and triphasic scan protocol usage increases the image quality at a reduced radiation dose.

  18. High-precision quadruple isotope dilution method for simultaneous determination of nitrite and nitrate in seawater by GCMS after derivatization with triethyloxonium tetrafluoroborate

    Energy Technology Data Exchange (ETDEWEB)

    Pagliano, Enea, E-mail: enea.pagliano@nrc-cnrc.gc.ca; Meija, Juris; Mester, Zoltán

    2014-05-01

    Highlights: • High-precision determination of nitrite and nitrate in seawater. • Use of quadruple isotope dilution. • Aqueous Et₃O⁺BF₄]⁻ derivatization chemistry for GCMS analysis of nitrite and nitrate. Abstract: Quadruple isotope dilution mass spectrometry (ID⁴MS) has been applied for simultaneous determination of nitrite and nitrate in seawater. ID⁴MS allows high-precision measurements and entails the use of isotopic internal standards (¹⁸O-nitrite and ¹⁵N-nitrate). We include a tutorial on ID⁴MS outlining optimal experimental design which generates results with low uncertainties and obviates the need for direct (separate) evaluation of the procedural blank. Nitrite and nitrate detection was achieved using a headspace GCMS procedure based on single-step aqueous derivatization with triethyloxonium tetrafluoroborate at room temperature. In this paper the sample preparation was revised and fundamental aspects of this chemistry are presented. The proposed method has detection limits in the low parts-per-billion for both analytes, is reliable, precise, and has been validated using a seawater certified reference material (MOOS-2). Simplicity of the experimental design, low detection limits, and the use of quadruple isotope dilution makes the present method superior to the state-of-the-art for determination of nitrite and nitrate, and an ideal candidate for reference measurements of these analytes in seawater.

  19. Endoscopic Therapy of Refractory Post-Papillotomy Bleeding With Electrocautery Forceps Coagulation Method Combined With Prophylactic Pancreatic Stenting

    Directory of Open Access Journals (Sweden)

    Zsolt Dubravcsik

    2014-01-01

    Conclusion: We presented a new, effective and safe second line endoscopic hemostatic method in patients with therapy resistant post-papillotomy bleeding. Combination of prophylactic pancreatic stenting and thermal coagulation with coagulation forceps might be suggested as a rescue treatment in patients with severe post-papillotomy bleeding, resistant to standard endoscopic therapy.

  20. Standart üçlü tedavi ile eradikasyon sağlanamayan Helicobacter pylori enfeksiyonunda lansoprazol, ranitidin bizmut sitrat, tetrasiklin ve metronidazolden oluşan dörtlü tedavinin etkinliği

    OpenAIRE

    AYDEMİR, Selim; BAYRAKTAROĞLU, Taner; ÜSTÜNDAĞ, Yücel; BORAZAN, Ali; SEKİTMEZ, Nedret; AKTUNÇ, Erol; NUMANOĞLU, Gamze

    2015-01-01

    Background/aim: Successful eradication of Helicobacter pylori (H. pylori) infection after failure of standard triple therapy is difficult. There are no guidelines on second-line therapies for H. pylori eradication failures. In the present study we investigated the efficacy of a 14-day quadruple regimen combining lansoprazole, ranitidine bismuth citrate (RBC), tetracycline and metronidazole as rescue treatment for Helicobacter pylori infection after failure of standard triple therapy com...

  1. 3+ and [Sb13Se16Br2] 5+ - Double and quadruple spiro cubanes from ionic liquids

    KAUST Repository

    Ahmed, Ejaz

    2014-01-08

    The reaction of antimony and selenium in the bromine-rich Lewis acidic ionic liquid [BMIm]Br·4.7AlBr3 (BMIm: 1-butyl-3- methylimidazolium) in the presence of a small amount of NbCl5 at 160 °C yielded dark-red crystals of [Sb7Se8Br 2][AlX4]3. For X = Cl0.15(1)Br 0.85(1), the compound is isostructural to [Sb7S 8Br2][AlCl4]3 [P212 121, a = 12.5132(5) Å, b = 17.7394(6) Å, c = 18.3013(6) Å]. For a higher chlorine content, X = Cl 0.58(1)Br0.42(1), a slightly disordered variant with a bisected unit cell is found [P21212, a = 12.3757(3) Å, b = 17.4116(5) Å, c = 9.0420(2) Å]. The [Sb 7Se8Br2]3+ heteropolycation (C 2 symmetry) is a spiro double-cubane with an antimony atom on the shared corner. From this distorted octahedrally coordinated central atom, tricoordinate selenium and antimony atoms alternate in the bonding sequence. The terminal antimony atoms each bind to a bromine atom. Quantum chemical calculations confirm polar covalent Sb-Se bonding within the cubes and indicate three-center, four-electron bonds for the six-coordinate spiro atoms. The calculated charge distribution reflects the electron-donor role of the antimony atoms. The use of a chlorine-rich ionic liquid resulted in the formation of triclinic [Sb13Se16Br2][AlX4] 5 with X = Cl0.80(1)Br0.20(1) [P$\\\\bar {1}$, a = 9.0842(5) Å, b = 19.607(1) Å, c = 21.511(1) Å, α = 64.116(6), β = 79.768(7), γ = 88.499(7)]. The cationic cluster [Sb13Se16Br2]5+ is a bromine-terminated spiro quadruple-cubane. This 31 atom concatenation of four cubes is assumed to be the largest known discrete main group polycation. A similar reaction in a chloride-free system yielded [Sb7Se 8Br2][Sb13Se16Br2] [AlBr4]8. In its monoclinic structure [P2/c, a = 27.214(5) Å, b = 9.383(2) Å, c = 22.917(4) Å, β = 101.68(1)], the two types of polycations alternate in layers along the a axis. In the series [Sb4+3nSe4+4nBr2](2+n)+, these cations are the members with n = 1 and 3. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGa

  2. Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure

    NARCIS (Netherlands)

    Feng, Yanfang; Händel, Nadine; de Groot, Marnix H. P.; Brul, Stanley; Schultsz, Constance; ter Kuile, Benno H.

    2014-01-01

    Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations

  3. Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps

    DEFF Research Database (Denmark)

    Amaral, L; Martins, M; Viveiros, M

    2008-01-01

    -TB) - a M. tuberculosis organism that is resistant to the most effective second line drugs available for the treatment of TB. This review provides detailed, significant evidence that supports the use of an old neuroleptic compound, thioridazine (TZ), for the management of MDR-TB and XDR-TB infections...... therapy predictably ineffective and death is inevitable, compassionate therapy with TZ should be contemplated. The risks are small and the rewards great....

  4. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort.

    Science.gov (United States)

    Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

    2015-06-30

    Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.

  5. Susceptibility tests to second line drugs and re-treatment of tuberculosis: Revisiting Early Experiences Las pruebas de sensibilidad a drogas de segunda línea y el re-tratamiento de la tuberculosis: Visión retrospectiva de tres estudios

    Directory of Open Access Journals (Sweden)

    Isabel N. De Kantor

    2007-06-01

    Full Text Available The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistanceto all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.La correlación entre resultados de pruebas de sensibilidad a drogas antituberculosas de segunda línea y evolución de los pacientes en tratamiento, aún es discutida. Se reanalizan aquí tres estudios realizados en la década del 60, sobre la relaci

  6. Quadruple burden of HIV/AIDS, tuberculosis, chronic intestinal parasitoses, and multiple micronutrient deficiency in ethiopia: a summary of available findings.

    Science.gov (United States)

    Amare, Bemnet; Moges, Beyene; Mulu, Andargachew; Yifru, Sisay; Kassu, Afework

    2015-01-01

    Human immunodeficiency virus (HIV), tuberculosis (TB), and helminthic infections are among the commonest public health problems in the sub-Saharan African countries like Ethiopia. Multiple micronutrient deficiencies also known as the "hidden hunger" are common in people living in these countries either playing a role in their pathogenesis or as consequences. This results in a vicious cycle of multiple micronutrient deficiencies and infection/disease progression. As infection is profoundly associated with nutritional status resulting from decreased nutrient intake, decreased nutrient absorption, and nutrient losses, micronutrient deficiencies affect immune system and impact infection and diseases progression. As a result, micronutrients, immunity, and infection are interrelated. The goal of this review is therefore to provide a summary of available findings regarding the "quadruple burden trouble" of HIV, TB, intestinal parasitic infections, and multiple micronutrient deficiencies to describe immune-modulating effects related to disorders.

  7. Identification and quantification of flavonoids and chromes in Baeckea frutescens by using HPLC coupled with diode-array detection and quadruple time-of-flight mass spectrometry.

    Science.gov (United States)

    Jia, Bei-Xi; Huangfu, Qian-Qian; Ren, Feng-Xiao; Jia, Lu; Zhang, Yan-Bing; Liu, Hong-Min; Yang, Jie; Wang, Qiang

    2015-01-01

    This article marks the first report on high-performance liquid chromatography (HPLC) coupled with diode-array detection (DAD) and quadruple time-of-flight mass spectrometry (Q-TOF/MS) for the identification and quantification of main bioactive constituents in Baeckea frutescens. In total, 24 compounds were identified or tentatively characterised based on their retention behaviours, UV profiles and MS fragment information. Furthermore, a validated method with good linearity, sensitivity, precision, stability, repeatability and accuracy was successfully applied for simultaneous determination of five flavonoids and one chromone in different plant parts of B. frutescens collected at different harvest times, and their dynamic contents revealed the appropriate harvest times. The established HPLC-DAD-Q-TOF/MS using multi-bioactive markers was proved to be a validated strategy for the quality evaluation on both raw materials and related products of B. frutescens.

  8. Roughness and uniformity improvements on self-aligned quadruple patterning technique for 10nm node and beyond by wafer stress engineering

    Science.gov (United States)

    Liu, Eric; Ko, Akiteru; O'Meara, David; Mohanty, Nihar; Franke, Elliott; Pillai, Karthik; Biolsi, Peter

    2017-05-01

    Dimension shrinkage has been a major driving force in the development of integrated circuit processing over a number of decades. The Self-Aligned Quadruple Patterning (SAQP) technique is widely adapted for sub-10nm node in order to achieve the desired feature dimensions. This technique provides theoretical feasibility of multiple pitch-halving from 193nm immersion lithography by using various pattern transferring steps. The major concept of this approach is to a create spacer defined self-aligned pattern by using single lithography print. By repeating the process steps, double, quadruple, or octuple are possible to be achieved theoretically. In these small architectures, line roughness control becomes extremely important since it may contribute to a significant portion of process and device performance variations. In addition, the complexity of SAQP in terms of processing flow makes the roughness improvement indirective and ineffective. It is necessary to discover a new approach in order to improve the roughness in the current SAQP technique. In this presentation, we demonstrate a novel method to improve line roughness performances on 30nm pitch SAQP flow. We discover that the line roughness performance is strongly related to stress management. By selecting different stress level of film to be deposited onto the substrate, we can manipulate the roughness performance in line and space patterns. In addition, the impact of curvature change by applied film stress to SAQP line roughness performance is also studied. No significant correlation is found between wafer curvature and line roughness performance. We will discuss in details the step-by-step physical performances for each processing step in terms of critical dimension (CD)/ critical dimension uniformity (CDU)/line width roughness (LWR)/line edge roughness (LER). Finally, we summarize the process needed to reach the full wafer performance targets of LWR/LER in 1.07nm/1.13nm on 30nm pitch line and space pattern.

  9. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study.

    Science.gov (United States)

    Saab, Charles; Al-Saber, Feryal A; Haddad, Jihad; Jallo, Mahir Khalil; Steitieh, Habib; Bader, Giovanni; Ibrahim, Mohamed

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE) assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs) versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates). Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies) based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1cvildagliptin and 2,267 received other OADs. Overall, the mean (±standard deviation) age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, Pvildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75-2.25) and 2.8 (95% confidence interval 2.5-3.2), respectively, in favor of vildagliptin. Vildagliptin achieved a numerically greater reduction in HbA1c (1.7%) from baseline versus comparator OADs (1.4%). The overall incidence of adverse events was comparable between studied cohorts. In real life, treatment with vildagliptin was associated with

  10. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study

    Directory of Open Access Journals (Sweden)

    Saab C

    2015-02-01

    Full Text Available Charles Saab,1 Feryal A Al-Saber,2 Jihad Haddad,3 Mahir Khalil Jallo,4 Habib Steitieh,5 Giovanni Bader,6 Mohamed Ibrahim,7 1Department of Endocrinology and Metabolism, Sacre Coeur University Hospital, Baabda, Lebanon; 2Endocrine Department, Bahrain Defence Force Hospital, Rifaa, Bahrain; 3Division of Endocrinology Department of Internal Medicine, Prince Hamaza Hospital, Amman, Jordan; 4Department of Internal Medicine, Gulf Medical University, Ajman, United Arab Emirates; 5New Mowasat Hospital, Safat, Kuwait; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharma Services AG, Dubai, United Arab Emirates Background: Type 2 diabetes mellitus (T2DM is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates. Methods: Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain ≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1c <7% without hypoglycemia or weight gain. Change in HbA1c from baseline to study endpoint and safety were also

  11. The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study.

    Science.gov (United States)

    Malva, João O; Amado, Alda; Rodrigues, Alexandra; Mota-Pinto, Anabela; Cardoso, Ana F; Teixeira, Ana M; Todo-Bom, Ana; Devesa, António; Ambrósio, António F; Cunha, António L; Gomes, Bárbara; Dantas, Carina; Abreu, Cidalina; Santana, Isabel; Bousquet, Jean; Apóstolo, João; Santos, Lúcia; Meneses de Almeida, Lúcio; Illario, Maddalena; Veríssimo, Rafaela; Rodrigues, Vitor; Veríssimo, Manuel T

    2018-01-01

    Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal). Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement, across Europe, is

  12. Synthesis and properties of a new quadruple perovskite: A-site ordered PbMn{sub 3}Mn{sub 4}O{sub 12}

    Energy Technology Data Exchange (ETDEWEB)

    Locherer, T.; Dinnebier, R.; Kremer, R.K. [Max Planck Institute for Solid State Research, Heisenbergstr. 1, D-70569 Stuttgart (Germany); Greenblatt, M., E-mail: martha@rutchem.rutgers.edu [Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854 (United States); Jansen, M. [Max Planck Institute for Solid State Research, Heisenbergstr. 1, D-70569 Stuttgart (Germany)

    2012-06-15

    PbMn{sub 3}Mn{sub 4}O{sub 12} a quadruple perovskite was prepared by high pressure and high temperature synthesis. Powder X-ray diffraction (PXD) and differential scanning calorimetry reveal a structural phase transition at {approx}380 K. Rietveld refinement of the synchrotron room temperature data indicate rhombohedral symmetry (R-3) with a=6.43675(4) A and {alpha}=109.556(2) Degree-Sign . Similar 423 K PXD data refined in a body centered cubic cell (Im-3) with a=7.4283(9) A. The temperature variation of magnetization, shows a magnetic field dependent antiferromagnetic-like transition at 68 K, and dynamic fluctuations indicative of magnetic frustration. The semiconducting electrical behavior indicates a large decrease in the conductivity near 68 K. The temperature dependence of the real part of the dielectric constant, {epsilon}{sub real} increases dramatically at {approx}68 K, and shows relaxor-type ferroelectric behavior as a function of frequency. The intimate coupling of magnetic, electrical and dielectric properties at 68 K in PbMn{sub 3}Mn{sub 4}O{sub 12} suggests possible multiferroic behavior. - Graphical abstract: Resistance vs. temperature plot showing drastically increasing resistances at temperatures below 68 K (a). Formation of a frequency dependency of the dielectric constant between 68 K and ambient temperature (b). Sharp cusp in the magnetic susceptibility observed at 68 K which is suppressed with increasing magnetic field (c) indicates coupling of magnetic, electric and dielectric effects. Highlights: Black-Right-Pointing-Pointer PbMn{sub 3}Mn{sub 4}O{sub 12} a quadruple perovskite was prepared at high pressure. Black-Right-Pointing-Pointer A structural transition is seen at 380 K from space group R-3-to-Im-3. Black-Right-Pointing-Pointer An antiferromagnetic transition is observed at 68 K. Black-Right-Pointing-Pointer It is semiconducting with a large decrease in the conductivity near 68 K. Black-Right-Pointing-Pointer The temperature dependence

  13. Influence of intramolecular f-f interactions on nuclear spin driven quantum tunneling of magnetizations in quadruple-decker phthalocyanine complexes containing two terbium or dysprosium magnetic centers.

    Science.gov (United States)

    Fukuda, Takamitsu; Matsumura, Kazuya; Ishikawa, Naoto

    2013-10-10

    Nuclear spin driven quantum tunneling of magnetization (QTM) phenomena, which arise from admixture of more than two orthogonal electronic spin wave functions through the couplings with those of the nuclear spins, are one of the important magnetic relaxation processes in lanthanide single molecule magnets (SMMs) in the low temperature range. Although recent experimental studies have indicated that the presence of the intramolecular f-f interactions affects their magnetic relaxation processes, little attention has been given to their mechanisms and, to the best of our knowledge, no rational theoretical models have been proposed for the interpretations of how the nuclear spin driven QTMs are influenced by the f-f interactions. Since quadruple-decker phthalocyanine complexes with two terbium or dysprosium ions as the magnetic centers show moderate f-f interactions, these are appropriate to investigate the influence of the f-f interactions on the dynamic magnetic relaxation processes. In the present paper, a theoretical model including ligand field (LF) potentials, hyperfine, nuclear quadrupole, magnetic dipolar, and the Zeeman interactions has been constructed to understand the roles of the nuclear spins for the QTM processes, and the resultant Zeeman plots are obtained. The ac susceptibility measurements of the magnetically diluted quadruple-decker monoterbium and diterbium phthalocyanine complexes, [Tb-Y] and [Tb-Tb], have indicated that the presence of the f-f interactions suppresses the QTMs in the absence of the external magnetic field (H(dc)) being consistent with previous reports. On the contrary, the faster magnetic relaxation processes are observed for [Tb-Tb] than [Tb-Y] at H(dc) = 1000 Oe, clearly demonstrating that the QTMs are rather enhanced in the presence of the external magnetic field. Based on the calculated Zeeman diagrams, these observations can be attributed to the enhanced nuclear spin driven QTMs for [Tb-Tb]. At the H(dc) higher than 2000 Oe, the

  14. The Quadruple Helix-Based Innovation Model of Reference Sites for Active and Healthy Ageing in Europe: The Ageing@Coimbra Case Study

    Directory of Open Access Journals (Sweden)

    João O. Malva

    2018-05-01

    Full Text Available Challenges posed by demographic changes and population aging are key priorities for the Horizon 2020 Program of the European Commission. Aligned with the vision of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA, the development, exchange, and large-scale adoption of innovative good practices is a key element of the responses required to ensure all European citizens remain as active and healthy as possible as they age. Urged by the need of developing scalable disruptive innovation across Europe, the European Commission and the EIP on AHA created the Reference Sites; local coalition of partners that develop good practices to support AHA. Ageing@Coimbra is an example of how this can be achieved at a regional level. The consortium comprises over 70 institutions that develop innovative practices to support AHA in Portugal. Ageing@Coimbra partners support a regional network of stakeholders that build a holistic ecosystem in health and social care, taking into consideration the specificities of the territories, living environments and cultural resources (2,243,934 inhabitants, 530,423 aged 65 or plus live in the Centre Region of Portugal. Good practices in reducing the burden of brain diseases that affect cognition and memory impairment in older people and tackling social isolation in urban and rural areas are among the top priorities of Ageing@Coimbra. Profiting from the collaborative work of academia, business companies, civil society, and authorities, the quadruple helix of Ageing@Coimbra supports: early diagnosis of frailty and disease; care and cure; and active, assisted, and independent living. This paper describes, as a Community Case Study, the creation of a Reference Site of the EIP on AHA, Ageing@Coimbra, and its impact in Portugal. This Reference Site can motivate other regions to develop innovative formulas to federate stakeholders and networks, building consortia at regional level. This growing movement

  15. Simulation study on control of spill structure of slow extracted beam from a medical synchrotron with feed-forward and feedback using a fast quadruple magnet and RF-knockout system

    Energy Technology Data Exchange (ETDEWEB)

    Muraoka, Ryo; Nakanishi, Tetsuya, E-mail: nakanishi.tetsuya@nihon-u.ac.jp

    2017-02-21

    A feedback control of the spill structure for the slow beam extraction from the medical synchrotron using a fast quadruple and radio frequency (RF)-knockout (QAR method) is studied to obtain the designed spill structure. In addition the feed-forward control is used so that the feedback control is performed effectively. In this extraction method, the spill of several ms are extracted continuously with an interval time of less than 1 ms. Beam simulation showed that a flat spill structure was effectively obtained with feed-forward and feedback control system as well as a step-wise structure which is useful for the shortening of an irradiation time in a spot scanning operation. The effect of current ripples from main quadruple magnet's power supplies could be also reduced with the feedback control application.

  16. On a clean power generation system with the co-gasification of biomass and coal in a quadruple fluidized bed gasifier.

    Science.gov (United States)

    Yan, Linbo; He, Boshu

    2017-07-01

    A clean power generation system was built based on the steam co-gasification of biomass and coal in a quadruple fluidized bed gasifier. The chemical looping with oxygen uncoupling technology was used to supply oxygen for the calciner. The solid oxide fuel cell and the steam turbine were combined to generate power. The calcium looping and mineral carbonation were used for CO 2 capture and sequestration. The aim of this work was to study the characteristics of this system. The effects of key operation parameters on the system total energy efficiency (ŋ ten ), total exergy efficiency (ŋ tex ) and carbon sequestration rate (R cs ) were detected. The energy and exergy balance calculations were implemented and the corresponding Sankey and Grassmann diagrams were drawn. It was found that the maximum energy and exergy losses occurred in the steam turbine. The system ŋ ten and ŋ tex could be ∼50% and ∼47%, and R cs could be over unit. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry.

    Science.gov (United States)

    Ouyang, Yilan; Zeng, Yangyang; Rong, Yinxiu; Song, Yue; Shi, Lv; Chen, Bo; Yang, Xinlei; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

    2015-09-01

    Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.

  18. Reduction of a cerium(III) siloxide complex to afford a quadruple-decker arene-bridged cerium(II) sandwich

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Rory P.; Scopelliti, Rosario; Mazzanti, Marinella [Institut des Sciences et Ingenierie Chimiques, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland); Maron, Laurent [Laboratoire de Physique et Chimie des Nano-objets, Institut National des Sciences Appliquees, Toulouse (France)

    2017-12-04

    Organometallic multi-decker sandwich complexes containing f-elements remain rare, despite their attractive magnetic and electronic properties. The reduction of the Ce{sup III} siloxide complex, [KCeL{sub 4}] (1; L=OSi(OtBu){sub 3}), with excess potassium in a THF/toluene mixture afforded a quadruple-decker arene-bridged complex, [K(2.2.2-crypt)]{sub 2}[{(KL_3Ce)(μ-η"6:η"6-C_7H_8)}{sub 2}Ce] (3). The structure of 3 features a [Ce(C{sub 7}H{sub 8}){sub 2}] sandwich capped by [KL{sub 3}Ce] moieties with a linear arrangement of the Ce ions. Structural parameters, UV/Vis/NIR data, and DFT studies indicate the presence of Ce{sup II} ions involved in δ bonding between the Ce cations and toluene dianions. Complex 3 is a rare lanthanide multi-decker complex and the first containing non-classical divalent lanthanide ions. Moreover, oxidation of 1 by AgOTf (OTf=O{sub 3}SCF{sub 3}) yielded the Ce{sup IV} complex, [CeL{sub 4}] (2), showing that siloxide ligands can stabilize Ce in three oxidation states. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Cycloserine Induced Psychosis among Patient's on Second Line ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    they may cause anxiety and lead to default and poor adherence by patients if quick recognition and intervention is ... neuropsychiatry effects such as headaches, depression, seizures, sleep disorders, psychoses and other .... psychiatric illness or hypertension. Her baseline investigations on admission which included serum ...

  20. 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.

  1. Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

    Science.gov (United States)

    Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

    2016-06-01

    Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration. © The Author(s) 2015.

  2. Guidelines for antiretroviral therapy in adults

    Directory of Open Access Journals (Sweden)

    G Meintjes

    2012-08-01

    Full Text Available These guidelines are intended as an update to those published in the Southern African Journal of HIV Medicine in January 2008. Since the release of the previous guidelines, the scale-up of antiretroviral therapy (ART in Southern Africa has continued to grow. Cohort studies from the region show excellent clinical outcomes; however, ART is still being started late (in advanced disease, resulting in relatively high early mortality rates. New data on antiretroviral (ARV tolerability in the region and several new ARV drugs have become available. Although currently few in number, some patients in the region are failing protease inhibitor (PI-based second-line regimens. To address this, guidelines on third-line (or ‘salvage’ therapy have been expanded.

  3. Predictors of switch to and early outcomes on third-line antiretroviral therapy at a large public-sector clinic in Johannesburg, South Africa.

    Science.gov (United States)

    Evans, Denise; Hirasen, Kamban; Berhanu, Rebecca; Malete, Given; Ive, Prudence; Spencer, David; Badal-Faesen, Sharlaa; Sanne, Ian M; Fox, Matthew P

    2018-04-10

    While efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes. Retrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load third-line ART. Among 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively. Our results show that the need for third-line is low (5%), but that patients' who switch to third-line ART have good early treatment

  4. Recent advances in targeted drug therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    FAN Yongqiang

    2018-02-01

    Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

  5. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    Directory of Open Access Journals (Sweden)

    Prisco L

    2011-08-01

    Full Text Available Lara Prisco1, Mario Ganau2, Federica Bigotto1, Francesca Zornada11Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Hospital of Cattinara, 2Graduate School of Nanotechnology, University of Trieste, ItalyAbstract: Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.Keywords: trigeminal neuralgia, antiepileptic drugs, combination therapy

  6. Targeted therapies in the treatment of urothelial cancers.

    Science.gov (United States)

    Aragon-Ching, Jeanny B; Trump, Donald L

    2017-07-01

    Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. HER-2-positive metastatic breast cancer: new possibilities for therapy

    Directory of Open Access Journals (Sweden)

    E. V. Artamonova

    2013-01-01

    Full Text Available This article is devoted to modern approaches in HER-2-positive metastatic breast cancer therapy. Recently treatment algorithm for this type of cancer included trastuzumab plus cytostatic in first line, continuation of trastuzumab with another chemotherapy regimen in second line, further switch to lapatinib and eventual return to trastuzumab after progression. Nowadays our options are broader owing to new anti-HER-2 agents which are pertruzumab and T-DM1. Now the most effective therapy regimen in first line is double HER-2 blockade (trastuzumab + pertuzumab in combination with docetaxel. Benefit of new agent T-DM1 versus combination of lapatinib and capecitabin is proved in patients progressed on trastuzumab and taxanes. T-DM1 also showed high efficacy as salvage therapy in intensively pretreated patients with meta- static HER-2-positive breast cancer who progressed on taxanes, trastuzumab and lapatinib.

  8. Maintenance therapy in advanced non-small cell lung cancer: current status and future implications.

    Science.gov (United States)

    Stinchcombe, Thomas E; Socinski, Mark A

    2011-01-01

    Maintenance therapy for patients with advanced non-small cell lung cancer has been an area of intense investigation. Maintenance therapy has been divided into two broad categories: continuation maintenance when the chemotherapy or targeted agent was part of a defined number of cycles of combination therapy and in the absence of disease progression is continued as a single agent or switch maintenance when a third agent is initiated after four cycles of platinum-based double-agent chemotherapy in the absence of disease progression. Two monoclonal antibodies, cetuximab and bevacizumab, are used as continuation maintenance, but the incremental benefit of the maintenance therapy with these agents is undetermined. Phase III trials have not revealed an overall survival benefit for continuation maintenance chemotherapy, and this approach should be considered investigational. Phase III trials have demonstrated an improvement in overall survival with switch maintenance therapy with pemetrexed compared with placebo in patients with nonsquamous histology and erlotinib compared with placebo. Phase III trials have not revealed an improvement in quality of life with maintenance therapy. In the trials of maintenance therapy, 30 to 40% of patients enrolled in the observation or placebo arm did not receive second-line therapy, and among the patients who did receive second-line therapy, there was significant heterogeneity in the therapy. The development of maintenance therapy has raised issues about the role of treatment-free intervals in routine clinical care, trial design issues such as the optimal endpoint, the ethics of a placebo arm, and the implications of maintenance therapy for first-line trials.

  9. Targeted Therapies for Lung Cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E

    Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival.

  10. Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

    Science.gov (United States)

    Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

    2015-07-01

    Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence

  11. Sex Therapy

    Science.gov (United States)

    Sex therapy Overview Sex therapy is a type of psychotherapy — a general term for treating mental health problems by talking with a mental health professional. Through sex therapy, you can address concerns about sexual function, ...

  12. Family Therapy

    Science.gov (United States)

    Family therapy Overview Family therapy is a type of psychological counseling (psychotherapy) that can help family members improve communication and resolve conflicts. Family therapy is usually provided by a psychologist, ...

  13. The Use of Biologic Therapies in Uveitis.

    Science.gov (United States)

    Schwartzman, Sergio; Schwartzman, Monica

    2015-12-01

    Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective

  14. Switch in Therapy from Methylphenidate to Atomoxetine in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

    DEFF Research Database (Denmark)

    Warrer, Pernille; Thomsen, Per Hove; Dalsgaard, Søren

    2016-01-01

    to 2.5 years prior to switching. Most common reasons for switching were "adverse events" (AEs) (78%), "wish for more optimal day coverage" (24%), and "lack of efficacy" (16%). Other reasons for switching included "patient/parental request" (13%) and "noncompliance" (2%). Most common AEs leading...... switching to ATX, and the reasons leading to a switch in therapy. METHODS: We included 55 patients with ADHD who switched from first-line MPH to second-line ATX during January 01, 2012 and May 15, 2014. Patient and treatment characteristics along with clinical reasons for switching therapy were extracted...

  15. Merkel cell carcinoma: Epidemiology, pathogenesis, diagnosis and therapy.

    Science.gov (United States)

    Amaral, Teresa; Leiter, Ulrike; Garbe, Claus

    2017-12-01

    Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a neuroendocrine phenotype. Incidence varies according to the geographic regions but is overall increasing. Different risk factors have been identified namely advanced age, immunosuppression, and ultraviolet light exposure. An association between MCC and polyomavirus infection is known. However, the exact mechanism that leads to carcinogenesis is yet to be fully understood. Surgery when feasible is the recommended treatment for localized disease, followed by adjuvant radiation or chemoradiation. In the metastatic setting, chemotherapy has been the standard treatment. However, two recently published trials with immune checkpoint inhibitors in first and second line showed promising results with a tolerable safety profile and these might become the standard therapy shortly. Somatostatin receptors are expressed in many MCC but such expression is not associated with disease severity. Presently there are no biomarkers predictive of response that could help to better select patients to these new therapies, and additional research is essential.

  16. Ovarian carcinoma: Role of radiation therapy versus chemotherapy

    International Nuclear Information System (INIS)

    Shehata, W.M.; Meyer, R.L.; Cormier, W.J.; Jazy, F.K.

    1986-01-01

    The authors evaluated 83 patients with ovarian cancer who were irradiated or treated by a combination of cytoxan, adriamycin, and cisplatin. According to FIGO stage, eight patients had stage I disease, 12 had stage II disease, 61 had stage II disease and two has stage IV disease. Fifty patients had bulky disease and 33 had minimal disease of 2 cm or less. Sixty patients were irradiated to an open abdominopelvic field (30 Gy delivered over 4 weeks), with or without a pelvic boost. Fifty-five patients received combination chemotherapy and 30 received a single agent as initial therapy. The patients were divided into three groups. The 26 patients in group I received primary radiation therapy with or with out adjuvant single-agent chemotherapy, then combination chemotherapy to salvage. The 34 patients in group II were irradiated after chemotherapy, mainly combination chemotherapy, failed. The 23 patients in group III received, mainly combination chemotherapy with second-line drugs for salvage

  17. Long-term costs and health impact of continued global fund support for antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    John Stover

    Full Text Available BACKGROUND: By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy (ART in 104 low- and middle-income countries. We estimated the cost and health impact of continuing treatment for these patients through 2020. METHODS AND FINDINGS: Survival on first-line and second-line ART regimens is estimated based on annual retention rates reported by national AIDS programs. Costs per patient-year were calculated from country-reported ARV procurement prices, and expenditures on laboratory tests, health care utilization and end-of-life care from in-depth costing studies. Of the 3.5 million ART patients in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining ART falls from $1.9 billion in 2011 to $1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5% decline in first-line ARV prices and $150-370 million less with a 5%-12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T, or $200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by ART correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. CONCLUSIONS: Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011-2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens.

  18. A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria.

    Science.gov (United States)

    Gilks, Charles F; Walker, A Sarah; Munderi, Paula; Kityo, Cissy; Reid, Andrew; Katabira, Elly; Goodall, Ruth L; Grosskurth, Heiner; Mugyenyi, Peter; Hakim, James; Gibb, Diana M

    2013-01-01

    In low-income countries, viral load (VL) monitoring of antiretroviral therapy (ART) is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable. 3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded) or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s) in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4tiebreaker' of ≥250 cells/mm(3) for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 'clinical failures' would particularly avoid premature, costly switch to second-line ART.

  19. Feminist Therapy.

    Science.gov (United States)

    Laidlaw, Toni; Malmo, Cheryl

    1991-01-01

    Traces roots of feminist therapy and its independence from traditional and prevalent theories and therapy practices. Asserts that Freudian theory and humanistic assumptions are sexist and contribute to powerlessness of women. In contrast, feminist therapy is seen as dealing directly with client-counselor relationships, trust, advocacy, and…

  20. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  1. A quadruple mutant of Arabidopsis reveals a β-carotene hydroxylation activity for LUT1/CYP97C1 and a regulatory role of xanthophylls on determination of the PSI/PSII ratio.

    Science.gov (United States)

    Fiore, Alessia; Dall'Osto, Luca; Cazzaniga, Stefano; Diretto, Gianfranco; Giuliano, Giovanni; Bassi, Roberto

    2012-04-18

    Xanthophylls are oxygenated carotenoids playing an essential role as structural components of the photosynthetic apparatus. Xanthophylls contribute to the assembly and stability of light-harvesting complex, to light absorbance and to photoprotection. The first step in xanthophyll biosynthesis from α- and β-carotene is the hydroxylation of ε- and β-rings, performed by both non-heme iron oxygenases (CHY1, CHY2) and P450 cytochromes (LUT1/CYP97C1, LUT5/CYP97A3). The Arabidopsis triple chy1chy2lut5 mutant is almost completely depleted in β-xanthophylls. Here we report on the quadruple chy1chy2lut2lut5 mutant, additionally carrying the lut2 mutation (affecting lycopene ε-cyclase). This genotype lacks lutein and yet it shows a compensatory increase in β-xanthophylls with respect to chy1chy2lut5 mutant. Mutant plants show an even stronger photosensitivity than chy1chy2lut5, a complete lack of qE, the rapidly reversible component of non-photochemical quenching, and a peculiar organization of the pigment binding complexes into thylakoids. Biochemical analysis reveals that the chy1chy2lut2lut5 mutant is depleted in Lhcb subunits and is specifically affected in Photosystem I function, showing a deficiency in PSI-LHCI supercomplexes. Moreover, by analyzing a series of single, double, triple and quadruple Arabidopsis mutants in xanthophyll biosynthesis, we show a hitherto undescribed correlation between xanthophyll levels and the PSI-PSII ratio. The decrease in the xanthophyll/carotenoid ratio causes a proportional decrease in the LHCII and PSI core levels with respect to PSII. The physiological and biochemical phenotype of the chy1chy2lut2lut5 mutant shows that (i) LUT1/CYP97C1 protein reveals a major β-carotene hydroxylase activity in vivo when depleted in its preferred substrate α-carotene; (ii) xanthophylls are needed for normal level of Photosystem I and LHCII accumulation.

  2. A quadruple mutant of Arabidopsis reveals a β-carotene hydroxylation activity for LUT1/CYP97C1 and a regulatory role of xanthophylls on determination of the PSI/PSII ratio

    Directory of Open Access Journals (Sweden)

    Fiore Alessia

    2012-04-01

    Full Text Available Abstract Background Xanthophylls are oxygenated carotenoids playing an essential role as structural components of the photosynthetic apparatus. Xanthophylls contribute to the assembly and stability of light-harvesting complex, to light absorbance and to photoprotection. The first step in xanthophyll biosynthesis from α- and β-carotene is the hydroxylation of ε- and β-rings, performed by both non-heme iron oxygenases (CHY1, CHY2 and P450 cytochromes (LUT1/CYP97C1, LUT5/CYP97A3. The Arabidopsis triple chy1chy2lut5 mutant is almost completely depleted in β-xanthophylls. Results Here we report on the quadruple chy1chy2lut2lut5 mutant, additionally carrying the lut2 mutation (affecting lycopene ε-cyclase. This genotype lacks lutein and yet it shows a compensatory increase in β-xanthophylls with respect to chy1chy2lut5 mutant. Mutant plants show an even stronger photosensitivity than chy1chy2lut5, a complete lack of qE, the rapidly reversible component of non-photochemical quenching, and a peculiar organization of the pigment binding complexes into thylakoids. Biochemical analysis reveals that the chy1chy2lut2lut5 mutant is depleted in Lhcb subunits and is specifically affected in Photosystem I function, showing a deficiency in PSI-LHCI supercomplexes. Moreover, by analyzing a series of single, double, triple and quadruple Arabidopsis mutants in xanthophyll biosynthesis, we show a hitherto undescribed correlation between xanthophyll levels and the PSI-PSII ratio. The decrease in the xanthophyll/carotenoid ratio causes a proportional decrease in the LHCII and PSI core levels with respect to PSII. Conclusions The physiological and biochemical phenotype of the chy1chy2lut2lut5 mutant shows that (i LUT1/CYP97C1 protein reveals a major β-carotene hydroxylase activity in vivo when depleted in its preferred substrate α-carotene; (ii xanthophylls are needed for normal level of Photosystem I and LHCII accumulation.

  3. 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.

  4. What Is Music Therapy?

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is ...

  5. Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial.

    Science.gov (United States)

    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Nohr-Westphal, Constanze; Brockmann, Jens; Andrassy, Joachim; Reinke, Petra; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Pascher, Andreas; Illner, Wolf-Dieter; Banas, Bernhard; Jauch, Karl-Walter

    2010-07-27

    De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%). Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

  6. On the energy scale involved in the metal to insulator transition of quadruple perovskite EuCu3Fe4O12: infrared spectroscopy and ab-initio calculations.

    Science.gov (United States)

    Brière, B; Kalinko, A; Yamada, I; Roy, P; Brubach, J B; Sopracase, R; Zaghrioui, M; Phuoc, V Ta

    2016-06-27

    Optical measurements were carried out by infrared spectroscopy on AA'3B4O12 A-site ordered quadruple perovskite EuCu3Fe4O12 (microscopic sample) as function of temperature. At 240 K (=TMI), EuCu3Fe4O12 undergoes a very abrupt metal to insulator transition, a paramagnetic to antiferromagnetic transition and an isostructural transformation with an abrupt large volume expansion. Above TMI, optical conductivity reveals a bad metal behavior and below TMI, an insulating phase with an optical gap of 125 meV is observed. As temperature is decreased, a large and abrupt spectral weight transfer toward an energy scale larger than 1 eV is detected. Concurrently, electronic structure calculations for both high and low temperature phases were compared to the optical conductivity results giving a precise pattern of the transition. Density of states and computed optical conductivity analysis identified Cu3dxy, Fe3d and O2p orbitals as principal actors of the spectral weight transfer. The present work constitutes a first step to shed light on EuCu3Fe4O12 electronic properties with optical measurements and ab-initio calculations.

  7. Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy. Trends and perspectives

    Directory of Open Access Journals (Sweden)

    Guillermo D. Mazzolini

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC

  8. VNS Therapy versus the latest antiepileptic drug.

    Science.gov (United States)

    Ben-Menachem, Elinor; French, Jacqueline A

    2005-09-01

    kept in perspective. Pro VNS Therapy: VNS Therapy is no longer a new treatment for patients with refractory epilepsy. The first implant was performed in l988, and since then more than 30,000 patients have received this therapy. It is no longer considered an unusual or dangerous procedure, but it is still used almost exclusively for refractory epilepsy patients and it has not been generally accepted for use as a first line or even second line therapy. However, compared to the new AEDs, VNS Therapy has similar efficacy results in clinical trials and in many epilepsy syndromes and the long-term efficacy results are even more positive, with continued improvement in seizure reduction for up to two years. Two of the major reasons for not using VNS Therapy early are that it is a surgical procedure, and its safety during MRI procedures, especially with 3 Tesla, has not yet been elucidated. The safety profile of VNS Therapy is very favorable; the side effects being totally different from those seen with AEDs. The most important aspects are that there have been no pharmacological interactions, cognitive or sedative side effects reported, and it is safe for use in all age groups. Side effects are restricted to local irritation, hoarseness, coughing and, in a few cases, swallowing difficulties when the stimulator is on, but these tend to disappear with time. No idiosyncratic side effect has emerged during the 16 years of use. Compliance is guaranteed. The cost of the implantation of the VNS Therapy System, when spread out over 8 years (battery life), is actually less than the cost of using a new AED over an eight-year period, and real savings as regards hospital costs due to seizures can be expected.

  9. Use of Third Line Antiretroviral Therapy in Latin America

    Science.gov (United States)

    Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

    2014-01-01

    Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931

  10. Use of third line antiretroviral therapy in Latin America.

    Directory of Open Access Journals (Sweden)

    Carina Cesar

    Full Text Available Access to highly active antiretroviral therapy (HAART is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known.Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART.Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3% failed a second line regimen and 44 (0.8% received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18-2.00, p = 0.001, younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86-4.10, p<0.001, and prior AIDS (HR = 2.17, 95% CI 1.62-2.90, p<0.001.Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted.

  11. Proton therapy

    International Nuclear Information System (INIS)

    Smith, Alfred R

    2006-01-01

    Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

  12. Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review.

    Science.gov (United States)

    Kuo, Hung-Yang; Yeh, Kun-Huei

    2014-07-01

    The prognosis of advanced gastric cancer (AGC) remains poor despite therapeutic advances in recent decades. Several recent positive phase III trials established the efficacy of second-line chemotherapy for metastatic gastric cancer in prolonging overall survival. However, malnutrition and poor performance of AGC in late stages usually preclude such patients from intensive treatment. Many targeted-therapies failed to show a significant survival benefit in AGC, but have regained attention after the positive result of ramucirumab was announced last year. Among all targeted agents, only trastuzumab, a monoclonal antibody against Human epidermal growth factor receptor-2 (HER2) protein, has been proven as having survival benefit by addition to first-line chemotherapy. Herein we reported a patient who benefited from adding trastuzumab to the same second-line combination chemotherapy (paclitaxel, 5-fluorouracil, and leucovorin) upon progression of bulky liver metastases. At least five months of progression-free survival were achieved without any additional toxicity. We also reviewed literature of molecularly-targeted therapy for chemotherapy-refractory gastric cancer, including several large phase III trials (REGARD, GRANITE-1, EXPAND, and REAL-3) published in 2013-2014. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Conceptual and ion-optical designs of an isocentric gantry for light-ion cancer therapy

    International Nuclear Information System (INIS)

    Vorobiev, L.G.; Weick, H.; Wollnik, H.

    1998-02-01

    Conceptual and ion-optical designs of an isocentric gantry are presented. The gantry is designed for light-ion therapy using a 6 Tm carbon beam. Its main characteristics are: 5 m overall radius, 1.4 m drift to the patient, 20x10 cm 2 treatment field, and two-direction active parallel scanning of a fine focused pencil beam. To achieve these features, the beam scanners are optimally positioned upstream the last 90 bending section consisting of two 45 sector magnets with 4 oblique field boundaries and different apertures. The gantry concept is a compromise between 'barrel' and 'conical' gantry shapes and is likely the most space-saving configuration of single-plane isocentric gantries. This new so-called 'short barrel' configuration features also small aperture quadruple lenses, low intermediate dispersion and a fully achromatic beam transport system. Its overall dimensions stay close to the size of the existing proton gantries. (orig.)

  14. Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Ray EM

    2017-11-01

    Full Text Available Emily M Ray, Hanna K Sanoff Division of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, USA Abstract: The only US Food and Drug Administration (FDA-approved first-line systemic therapy for hepatocellular carcinoma (HCC is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin and GEMOX (gemcitabine-oxaliplatin. Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib. Keywords: liver cancer, chemotherapy, immunotherapy

  15. Febrile neutropenia in paediatric peripheral blood stem cell transplantation, in vitro sensitivity data and clinical response to empirical antibiotic therapy

    International Nuclear Information System (INIS)

    Ansari, S.H.; Nasim, S.; Ahmed, A.; Irfan, M.; Ishaque, A.; Farzana, T.; Panjwani, V.K.; Taj, M.; Shamsi, T.S.

    2006-01-01

    To find the in-vitro sensitivity data and clinical response in order to determine the changes required in empiric antibiotic therapy for management of febrile neutropenia in paediatric patients undergoing peripheral blood stem cell transplantation. All patients were treated according to institutional protocol for febrile neutropenia. Empirical antibiotics include Ceftriaxone and Amikacin. In non-responders, changes made included Imipenem and Amikacin, Piperacillin Tazobactum/Tiecoplanin or Vancomycin/Cloxacilin/Ceftazidime. In non-responders, amphotaracin was added until recovery. Out of 52 patients, 5 did not develop any fever; in the remaining 47 patients there were 57 episodes of febrile neutropenia. The mean days of febrile episodes were 4.71 (range 3-8). Fever of unknown origin (FUO) occurred in 31 (54.3%) episodes. Microbiologically documented infection (MDI) occurred in 17 (29.8%) episodes of fever. Clinically documented infection (CDI) occurred in 9 (15.7%) episodes. Gram-negative organisms were isolated in 10 while gram-positive organisms in 7. Klebseilla, S. aureus were the most common isolates. Empirical therapy was effective in 12 of the 33 (36%) episodes. Out of 28, 26 (92%) responded to Imipenem/Amikacin as second line therapy while those who received any other second line combination, only 11 out of 22 (50%) showed response. Systemic Amphotericin was used in 4 patients, 2 responded. Infection related mortality rate was 4%. (author)

  16. Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy.

    Science.gov (United States)

    Kerschberger, Bernhard; Boulle, Andrew M; Kranzer, Katharina; Hilderbrand, Katherine; Schomaker, Michael; Coetzee, David; Goemaere, Eric; Van Cutsem, Gilles

    2015-01-01

    Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

  17. Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 2: fármacos de segunda linha Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 2: second line drugs

    Directory of Open Access Journals (Sweden)

    Marcos Abdo Arbex

    2010-10-01

    Full Text Available Os objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Descrevemos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no tratamento da tuberculose multidroga resistente (aminoglicosídeos, fluoroquinolonas, cicloserina/terizidona, etionamida, capreomicina e ácido para-aminossalicílico. Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal.The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs can make it necessary to modify or discontinue treatment. We describe the general mechanism of action, absorption, metabolization, and excretion of the drugs used to treat multidrug resistant tuberculosis (aminoglycosides, fluoroquinolones, cycloserine/terizidone, ethionamide, capreomycin, and para-aminosalicylic acid. We describe adverse drug reactions and interactions (with other drugs, food, and antacids, as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure.

  18. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

    2013-01-01

    standard temozolomide chemoradiotherapy and bevacizumab-containing second-line therapy, received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first...... eight weeks and at progression. The primary end-point was median progression-free survival (PFS) and secondary end-points were radiographic response, overall survival (OS), and safety of the bevacizumab-temsirolimus combination. RESULTS: Thirteen patients were included, whereof three went off....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

  19. Severe hepatocytolisis syndrome - a challenge in medical therapy of Cushing’s disease

    Directory of Open Access Journals (Sweden)

    Valea Ana

    2015-08-01

    Full Text Available Introduction Cushing’s disease is a rare endocrine disorder characterized by persistent hypercortisolism due to excessive, autonomous ACTH secretion by a pituitary adenoma. Transsphenoidal adenomectomy is the main therapeutic option in Cushing’s disease. When imaging studies are unable to demonstrate an obvious pituitary mass complete tumor resection is difficult and often encumbered by risk of relapse. Medical therapy is a second-line option or the first-line treatment for patients with high surgical risk, incomplete surgical resection or relapse. Rarely classic clinical manifestations limit the selection of medical therapy for Cushing’s disease. Case presentation We present the case of a male patient with Cushing’s disease complicated with diabetes mellitus and severe hepatocytolisis syndrome with no visible pituitary adenoma on MRI studies. In the absence of technical equipment petrosal sinus sampling could not be performed in order to improve surgery outcome

  20. Therapy of hyperthyroidism in pregnancy and breastfeeding.

    Science.gov (United States)

    Fumarola, Angela; Di Fiore, Agnese; Dainelli, Michela; Grani, Giorgio; Carbotta, Giovanni; Calvanese, Anna

    2011-06-01

    Uncontrolled hyperthyroidism in pregnancy is associated with an increased risk of perinatal complications. The state of the art discussed here has been derived through a wide MEDLINE search throughout English-language literature by using a combination of words such as hyperthyroidism, propylthiouracil (PTU), methimazole, rituximab, and pregnancy to identify original related works and review articles. Thioamides are the main first-line therapeutic options, whereas beta-blockers and iodine are second-choice drugs; surgery is resorted to only in exceptional cases. Methimazole and PTU reduce the production of thyroid hormones by selectively inhibiting thyroid peroxidase. PTU was once considered to be the first-choice drug in the treatment of gestational hyperthyroidism; however, the United States Food and Drug Administration now recommends it as a second-line thioamide, which should be used solely by women in their first trimester of pregnancy. Thyroidectomy is to be carried out only in pregnant women affected by life-threatening, uncontrollable hyperthyroidism, or in cases with thioamide intolerance. Obstetricians & Gynecologists, Family Physicians After completion of this article, the physician should be better able to choose appropriate therapies for hyperthyroidism in pregnant women, assess the risk of possible complications due to maternal hyperthyroidism, and evaluate strategies for patient follow-up.

  1. Play Therapy

    Science.gov (United States)

    Lawver, Timothy; Blankenship, Kelly

    2008-01-01

    Play therapy is a treatment modality in which the therapist engages in play with the child. Its use has been documented in a variety of settings and with a variety of diagnoses. Treating within the context of play brings the therapist and the therapy to the level of the child. By way of an introduction to this approach, a case is presented of a six-year-old boy with oppositional defiant disorder. The presentation focuses on the events and interactions of a typical session with an established patient. The primary issues of the session are aggression, self worth, and self efficacy. These themes manifest themselves through the content of the child’s play and narration of his actions. The therapist then reflects these back to the child while gently encouraging the child toward more positive play. Though the example is one of nondirective play therapy, a wide range of variation exists under the heading of play therapy. PMID:19724720

  2. Hormone Therapy

    Science.gov (United States)

    ... it also can be a sign of endometrial cancer. All bleeding after menopause should be evaluated. Other side effects reported by women who take hormone therapy include fluid retention and breast soreness. This soreness usually lasts for a short ...

  3. Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

    Science.gov (United States)

    Franceschi, Enrico; Lamberti, Giuseppe; Paccapelo, Alexandro; Di Battista, Monica; Genestreti, Giovenzio; Minichillo, Santino; Mura, Antonella; Bartolini, Stefania; Agati, Raffaele; Brandes, Alba A

    2018-04-18

    Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

  4. Manual Therapy

    OpenAIRE

    Hakgüder, Aral; Kokino, Siranuş

    2002-01-01

    Manual therapy has been used in the treatment of pain and dysfunction of spinal and peripheral joints for more than a hundred years. Manual medicine includes manipulation, mobilization, and postisometric relaxation techniques. The aim of manual therapy is to enhance restricted movement caused by blockage of joints keeping postural balance, restore function and maintain optimal body mechanics. Anatomic, biomechanical, and neurophysiological evaluations of the leucomotor system is essential for...

  5. Adaptive therapy.

    Science.gov (United States)

    Gatenby, Robert A; Silva, Ariosto S; Gillies, Robert J; Frieden, B Roy

    2009-06-01

    A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the "cost" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant

  6. Drug Therapy.

    Science.gov (United States)

    He, Ri-Hui; Tao, Ran

    2017-01-01

    This chapter first summarizes the therapy of addiction disorder, and elaborates on the progress of medication. First, the difference between dependency and addiction are introduced. The basic principles of the therapy of substance and non-substance addiction are then put forward. It is also pointed out in this chapter that with the progress of the study, the goal of addiction disorder therapy is expected to transfer from reducing the relapse and harm of the addiction to completely eliminating and recovering from it. This chapter also introduces the progress of psychological addiction elimination technology, especially the "Unconditioned Stimulus Retrieval Extinction Paradigm and Conditioned Stimulus Retrieval Extinction Paradigm" and PITDH technology. Finally it is pointed out that in addiction disorder therapy, comprehensive intervention has become a trend. With regard to the medication for addiction disorders, this chapter also includes the progress and deficiencies of substance and non-substance addiction. In terms of addiction disorder rehabilitation, the foundation of substance addiction is medication which is, however, limited for non-substance addiction. The key to the rehabilitation of addiction disorder is psycho-behavioral therapy, which is especially effective in eliminating craving.

  7. Neutron therapy

    International Nuclear Information System (INIS)

    Riesler, Rudi

    1995-01-01

    Standard radiotherapy uses Xrays or electrons which have low LET (linear energy transfer); in contrast, particles such as neutrons with high LET have different radiobiological responses. In the late 1960s, clinical trials by Mary Catterall at the Hammersmith Hospital in London indicated that fast neutron radiation had clinical advantages for certain malignant tumours. Following these early clinical trials, several cyclotron facilities were built in the 1980s for fast neutron therapy, for example at the University of Washington, Seattle, and at UCLA. Most of these newer machines use extracted cyclotron proton beams in the range 42 to 66 MeV with beam intensities of 15 to 60 microamps. The proton beams are transported to dedicated therapy rooms, where neutrons are produced from beryllium targets. Second-generation clinical trials showed that accurate neutron beam delivery to the tumour site is more critical than for photon therapy. In order to achieve precise beam geometries, the extracted proton beams have to be transported through a gantry which can rotate around the patient and deliver beams from any angle; also the neutron beam outline (''field shape'') must be adjusted to extremely irregular shapes using a flexible collimation system. A therapy procedure has to be appropriately organized, with physicians, radiotherapists, nurses, medical physicists and other staff in attendance; other specialized equipment, such as CT or MRI scanners and radiation simulators must be made available. Neutron therapy is usually performed only in radiation oncology departments of major medical centres

  8. Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Österlund, Pia; Berglund, Åke

    2017-01-01

    to select which older patients should receive therapy. Methods: The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m2 iv day 1 every 3 weeks or 180-250 mg/m2 iv...... day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m2 days 1-14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1-14 + irinotecan 180 mg/m2 day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full...... chance for tailored treatment strategies in these patients. Trial registration: EU Clinical Trial Register, EudraCT no. 2014-000394-39. Registered 05 May 2014....

  9. Coal could quadruple by 2000. [Canada

    Energy Technology Data Exchange (ETDEWEB)

    1979-03-01

    The federal and most provincial governments are encouraging coal as an energy source. Coal production will increase 4-5 times by 2000 and world trade double with further increases to 2025. The Canadian steel industry is producing near capacity and forecasts a growth rate of 4% over the next ten years. Problems facing Canadian steel industry include the E1k River project, St. Lawrence toll increases, environmental coal requirements, and Chinese crude steel. Coal industry should have an excellent future if the Canadian governments can fill their leadership roles.

  10. Systemic therapy for vulval Erosive Lichen Planus (the 'hELP' trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Simpson, Rosalind C; Murphy, Ruth; Bratton, Daniel J; Sydes, Matthew R; Wilkes, Sally; Nankervis, Helen; Dowey, Shelley; Thomas, Kim S

    2016-01-04

    Erosive lichen planus affecting the vulva (ELPV) is a relatively rare, chronic condition causing painful raw areas in the vulvovaginal region. Symptoms are pain and burning, which impact upon daily living. There is paucity of evidence regarding therapy. A 2012 Cochrane systematic review found no randomised controlled trials (RCTs) in this field. Topically administered corticosteroids are the accepted first-line therapy: however, there is uncertainty as to which second-line treatments to use. Several systemic agents have been clinically noted to show promise for ELPV refractory to topically administered corticosteroids but there is no RCT evidence to support these. The 'hELP' study is a RCT with an internal pilot phase designed to provide high-quality evidence. The objective is to test whether systemic therapy in addition to standard topical therapy is a beneficial second-line treatment for ELPV. Adjunctive systemic therapies used are hydroxychloroquine, methotrexate, mycophenolate mofetil and prednisolone. Topical therapy plus a short course of prednisolone given orally is considered the comparator intervention. The trial is a four-armed, open-label, pragmatic RCT which uses a blinded independent clinical assessor. To provide 80 % power for each comparison, 96 participants are required in total. The pilot phase aims to recruit 40 participants. The primary clinical outcome is the proportion of patients achieving treatment success at 6 months. 'Success' is defined by a composite measure of Patient Global Assessment score of 0 or 1 on a 4-point scale plus improvement from baseline on clinical photographs scored by a clinician blinded to treatment allocation. Secondary clinical outcomes include 6-month assessment of: (1) Reduction in pain/soreness; (2) Global assessment of disease; (3) Response at other affected mucosal sites; (4) Hospital Anxiety and Depression Scale scores; (5) Sexual function; (6) Health-related quality of life using 'Short Form 36' and 'Skindex

  11. Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

    Science.gov (United States)

    Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

    2017-12-01

    The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival

  12. Art Therapy

    DEFF Research Database (Denmark)

    Skov, Vibeke; Pedersen, Inge Nygaard

    2014-01-01

    Abstract Based on a Jungian approach, this article will introduce an integrative model to therapeutic change using art therapy methods as practical tools, with the aim of improving quality of life and in the prevention of depression. In a research study involving six participants, painting, clay...... work and drumming were used together with imagination and personal dialogues linked to the artwork. These art therapy processes attempted to combine the participant’s experience of inner and outer reality. The effect of gaining more knowledge about their inner reality using dreams and symbols......, was that participants gained a new understanding about their personal life. In addition, some participants were able to continue to use art therapy experiences as selfdevelopmental tools after the research study terminated. Jung’s description of the interactive relationship between the two living parts of the psyche...

  13. Oxygen Therapy

    Directory of Open Access Journals (Sweden)

    Bonnie Solmes

    2000-01-01

    Full Text Available LTOT is prescribed for people with chronic lung disease in whom there is a decrease in the ability of the lungs to supply enough oxygen to the body. The heart is obliged to pump faster to meet the body's oxygen requirements. This may place undue stress on the heart, resulting in palpitations, dizziness and fatigue. A low oxygen level in arterial blood is also harmful to the heart, the brain and the pulmonary blood vessels. Oxygen therapy is used to break this cycle. A person with low blood oxygen will often be able to accomplish more with less fatigue with the help of supplemental oxygen therapy. Shortness of breath is a mechanical problem resulting from the effects of chronic obstructive pulmonary disease. Oxygen therapy may or may not reduce shortness of breath, but it will help the lungs and heart to function with less stress.

  14. Music therapy

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung...... und Entwicklung Music Therapy Annual. Research and Development. 2005 (1), pp. 25-40. Reichert Verlag Wiesbaden....

  15. MODERN POSSIBILITIES OF THERAPY WITH INHIBITORS OF CONTROL POINTS IN METASTATIC UROTHELIAL CANCER

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2018-01-01

    Full Text Available For a long time, chemotherapy remained the main treatment option for metastatic urothelial carcinoma (mUC. Over the past year, there have been revolutionary changes associated with the approval of five new drugs aimed at blocking the interaction between the surface protein of T-lymphocytes PD-1 and its ligands PD-L1 and PD-L2, resulting in the activation of the immune response. It is noteworthy that the anti-PD-1 antibody pembrolizumab demonstrated an increase in overall survival relative to chemotherapy in a randomized phase III trial in the second line with mUC. Based on this level 1 evidence pembrolizumab was approved by the US Food and Drug Administration (FDA. Nivolumab (antibody PD-1 also demonstrated an increase in overall survival compared to historical control and was approved by FDA. Likewise, antibodies targeting PD-L1, including atezolizumab, durvalumab and avelumab, received accelerated approval from the FDA as the second line of treatment for mUC. Some of these agents are approved in the first line by the results of phase II study (atezolizumab and pembolizumab received accelerated approval for first-line treatment in patients not receiving cisplatin. Despite these many endorsements, clinical development of new biomarkers for selection of patients, who can get maximum advantages of immunotherapy and also for development the optimal therapy sequencing still are biggest and critical question for future investigation. The clinical introduction of biomarkers to determine optimal treatment of patients remains extremely important.

  16. Radiation therapy

    International Nuclear Information System (INIS)

    Peschel, R.E; Fisher, J.J.

    1986-01-01

    The new insights and controversies concerning the radiobiological properties of malignant melanoma and how these relate to new clinical approaches are reviewed. The recent clinical experience with large individual fraction sizes is analyzed. The treatment of malignant melanoma in certain specialized sites is also described. An attempt is made to place in perspective the usefulness of radiation therapy in the treatment of this complex disease. Finally, certain new applications for radiation therapy both alone and in combustion with other treatment modalities are proposed that may ultimately prove appropriate for clinical trials

  17. Greater Efficacy of Total Thyroidectomy versus Radioiodine Therapy on Hyperthyroidism and Thyroid-Stimulating Immunoglobulin Levels in Patients with Graves' Disease Previously Treated with Antithyroid Drugs

    Science.gov (United States)

    Kautbally, Shakeel; Alexopoulou, Orsalia; Daumerie, Chantal; Jamar, François; Mourad, Michel; Maiter, Dominique

    2012-01-01

    Aims We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid-stimulating immunoglobulins (TSI) in patients with Graves' disease. Methods We retrospectively studied 80 patients initially treated with antithyroid drugs and requiring either RAI (8.3 ± 1.7 mCi of 131I; n = 40) or TTx (n = 40) as second-line therapy. Results The TTx and RAI groups were not different, except for larger goiter, higher FT3 and more frequent Graves' orbitopathy at diagnosis in the surgery group (p antithyroid drugs. PMID:24783007

  18. Quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude root bark of Morus alba L.

    Science.gov (United States)

    Zhao, Yong; Kongstad, Kenneth Thermann; Jäger, Anna Katharina; Nielsen, John; Staerk, Dan

    2018-06-29

    In this paper, quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with HPLC-HRMS-SPE-NMR were used for studying the polypharmacological properties of crude root bark extract of Morus alba L. This species is used as an anti-diabetic principle in many traditional treatment systems around the world, and the crude ethyl acetate extract of M. alba root bark was found to inhibit α-glucosidase, α-amylase and protein-tyrosine phosphatase 1B (PTP1B) with IC 50 values of 1.70 ± 0.72, 5.16 ± 0.69, and 5.07 ± 0.68 μg/mL as well as showing radical scavenging activity equaling a TEAC value of (3.82 ± 0.14) × 10 4  mM per gram extract. Subsequent investigation of the crude extract using quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling provided a quadruple biochromatogram that allowed direct correlation of the HPLC peaks with one or more of the tested bioactivities. This was used to target subsequent HPLC-HRMS-SPE-NMR analysis towards peaks representing bioactive analytes, and led to identification of a new Diels-Alder adduct named Moracenin E as well as a series of Diels-Alder adducts and isoprenylated flavonoids as potent α-glucosidase and α-amylase inhibitors with IC 50 values in the range of 0.60-27.15 μM and 1.22-69.38 μM, respectively. In addition, these compounds and two 2-arylbenzofurans were found to be potent PTP1B inhibitors with IC 50 values ranging from 4.04 to 21.67 μM. The high-resolution radical scavenging profile also revealed that almost all of the compounds possess radical scavenging activity. In conclusion the quadruple high-resolution profiling method presented here allowed a detailed profiling of individual constituents in crude root bark extract of M. alba, and the method provides a general tool for detailed mapping of bioactive constituents in polypharmacological herbal remedies. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Radiation therapy

    International Nuclear Information System (INIS)

    Matsuura, Keiichi; Miyoshi, Makoto; Jinguu, Ken-ichi

    1982-01-01

    Of the cases of lung cancer in which radiation therapy was given between 1961 and November 1981, 399 cases for which histological type was confirmed, and irradiated as follows were reviewed. The cases of squamous cell carcinoma and adenocarcinoma irradiated with more than 5,000 rad or more, those of undifferentiated carcinoma irradiated with 3,000 rad or more, and those irradiated pre- and post-operatively with 3,000 rad or more. The actual 5 year survival rate for stages I, II, III and IV were 29.6, 9.3, 7.5 and 1.9% respectively, and the survival rate tended to be better for adenocarcinoma than squamous cell carcinoma at stages I, II and III, but not different at stage IV. There was no difference between large cell, small cell and squamous cell carcinomas. Irradiation with 200 rad every other day or 150 rad daily was better than that with 200 rad, and daily irradiation with 150 rad was used since 1976. The therapy of stage III small cell carcinoma at the age of up to 80 years was improved with the combination of anticancer agents, maintenance therapy and immunotherapy, but these combined therapies were not significantly effective for the cancers with other histological types or at other stages. Although there was no significant difference in statistics for resectable cases, clinically, the results were experienced to be better after resection, and surgery was done in combination as much as possible. (Kaihara, S.)

  20. Dance Therapy.

    Science.gov (United States)

    Leventhal, Marcia B.

    1980-01-01

    Dance therapy deals with personal growth via body-mind interaction. A change in movement expression is believed to result in a personality or behavior change. The therapist is trained to become sensitive to movement expression as it relates to the psychological, motor, and cognitive development of the child. (JN)

  1. Shock therapies.

    Science.gov (United States)

    Dean, Erin

    2016-02-03

    Therapies administered by mental health nurses, aimed at "curing" gay people of their sexual preference were still in common use in the UK in the 1960s and early 1970s. Some nurses tried to avoid participating in these practices, but many believed that they were helping their patients, as a new book reveals.

  2. Proton therapy

    International Nuclear Information System (INIS)

    Jongen, Y.

    1995-01-01

    Ideal radiotherapy deposits a large amount of energy in the tumour volume, and none in the surrounding healthy tissues. Proton therapy comes closer to this goal because of a greater concentration of dose, well defined proton ranges and points of energy release which are precisely known - the Bragg peak1. In the past, the development of clinical proton therapy has been hampered by complexity, size, and cost. To be clinically effective, energies of several hundred MeV are required; these were previously unavailable for hospital installations, and pioneering institutions had to work with complex, inadequate equipment originally intended for nuclear physics research. Recently a number of specialist organizations and commercial companies have been working on dedicated systems for proton therapy. One, IBA of Belgium, has equipment for inhouse hospital operation which encompasses a complete therapy centre, delivered as a turnkey package and incorporating a compact, automated, higher energy cyclotron with isocentric gantries. Their system will be installed at Massachusetts General Hospital, Boston. The proton therapy system comprises: - a 235 MeV isochronous cyclotron to deliver beams of up to 1.5 microamps, but with a hardware limitation to restrict the maximum possible dose; - variable energy beam (235 to 70 MeV ) with energy spread and emittance verification; - a beam transport and switching system to connect the exit of the energy selection system to the entrances of a number of gantries and fixed beamlines. Along the beam transport system, the beam characteristics are monitored with non-interceptive multiwire ionization chambers for automatic tuning; - gantries fitted with nozzles and beamline elements for beam control; both beam scattering and beam wobbling techniques are available for shaping the beam;

  3. Art Therapy: What Is Art Therapy?

    Science.gov (United States)

    ... individual, couples, family, and group therapy formats. Art therapy is an effective treatment for people experiencing developmental, medical, educational, and social or psychological impairment. Individuals who benefit from art therapy include ...

  4. Physical Therapy and Occupational Therapy in Progeria

    Science.gov (United States)

    Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation ... Inc. All rights reserved. Page 2 of 5 Physical and Occupational Therapy in Progeria Hutchinson-Gilford Progeria ...

  5. Music Therapy: A Career in Music Therapy

    Science.gov (United States)

    About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, cognitive, emotional, and social functioning. Music therapists work with children and adults with developmental ...

  6. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  7. Radioiodine therapy

    International Nuclear Information System (INIS)

    Torres, J.F. Jr.; Deliso, H.B.

    1992-01-01

    For over 40 years now, radioiodine ( 131 I) has remained one of the most useful radionuclide for diagnosis and therapy in Nuclear Medicine. The wide application of radioiodine in the study of the thyroid gland and in the management of its disorders has been most rewarding. The medical literature is replete with reports of its efficacy, failures, and complications, but most of these studies have been conducted among Caucasian persons and in relatively affluent societies. Very few reports are available from the less developed and economically depressed areas of the world where thyroid disorders abound or and are even endemic. This chapter is an attempt to highlight the use of radioactive iodine therapy in the developing countries, particularly those in the Asian region

  8. Particle therapy

    International Nuclear Information System (INIS)

    Raju, M.R.

    1993-01-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics

  9. Music Therapy

    DEFF Research Database (Denmark)

    Trondalen, Gro; Bonde, Lars Ole

    2012-01-01

    music therapy orientations/models (Guided Imagery and Music, Nordoff-Robbins, Psychoanalytic, Cognitive-behavioral etc), their theoretical foundations and their practical approaches to health and wellbeing or ‘health musicking’. The relational context – the interplay of (expressive as well as receptive......Music therapy (MT) is most commonly defined as an intervention where “the therapist helps the client to promote health, using music experiences and the relationships developing through them” (Bruscia 1998). Also other definitions of MT agree that a therapeutic relationship is important for a music...... intervention to be considered MT. Other interventions that “use music for health-related goals, but in ways that do not qualify as music therapy” (Gold 2009), may be described as music medicine, or simply as music listening. In this text we elaborate on an overview chapter covering some of the different major...

  10. Music Therapy

    DEFF Research Database (Denmark)

    Sanfi, Ilan

    2012-01-01

    may cause detrimental long-term effects. Three studies have examined the effect of music therapy procedural support (MTPS) under needle procedures. Consequently, this study aims at examining the effects of MTPS in an RCT. Moreover, the study addresses clinical aspects of the applied MT intervention...... and provides research-based clinical tools. Methods 41 children (1 to 10 years) were enrolled and underwent a single PIVA procedure. The children were randomly assigned to either an MT or a comparable control group receiving PIVA. In addition, the music therapy (MT) group received individualised MTPS (i.......e. music alternate engagement) before, during, and after PIVA. The intervention was performed by a trained music therapist and comprised preferred songs, improvised songs/music, and instrument playing. The study was carried out in accordance with the rules in force regarding research ethics and clinical MT...

  11. Radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Jr, J F; Deliso, H B

    1993-12-31

    For over 40 years now, radioiodine ({sup 131}I) has remained one of the most useful radionuclide for diagnosis and therapy in Nuclear Medicine. The wide application of radioiodine in the study of the thyroid gland and in the management of its disorders has been most rewarding. The medical literature is replete with reports of its efficacy, failures, and complications, but most of these studies have been conducted among Caucasian persons and in relatively affluent societies. Very few reports are available from the less developed and economically depressed areas of the world where thyroid disorders abound or and are even endemic. This chapter is an attempt to highlight the use of radioactive iodine therapy in the developing countries, particularly those in the Asian region

  12. [Case Report: Clindamycin with Primaquine Therapy for Severe Pneumocystis Pneumonia].

    Science.gov (United States)

    Yoshimura, Yukihiro; Sakamoto, Youhei; Amano, Yuichiro; Tachikawa, Natsuo

    2015-09-01

    A Japanese female in her 60's on 5 years' treatment with prednisolone 5 mg for ulcetarive colitis developed severe bloody stools and diarrhea and was admitted. A total colectomy was performed because leukocytapheresis with intravenous corticosteroid administration (prednisolone 70 mg/day) relieved her symptoms partially. Pneumocystis pneumonia (PCP) prophylaxis was not introduced then. She developed acute respiratory failure on postoperative day (POD) 8, and was intubated and moved to our intensive care unit. PCP was suspected and sulfamethoxazole/trimethoprim (ST) was started with methylprednisolone 40 mg/day. The pneumonia initially improved but got worse around POD 27 and pulse corticosteroid therapy was administered. Antibiotics were first changed to pentamidine and finally changed to clindamycin/primaquine because of adverse reactions due to both of the medications. She recovered fully and experienced no exacerbation after discontinuation of the secondary prophylaxis. This is the first report of primaquine administration for PCP in Japan. Clindamycin/primaquine are second-line drugs but very important because the first-line medications such as ST and pentamidine cause adverse reactions and frequently result in discontinuation, as was the case in our present patient. Nowadays immunosuppresive therapy for malingnancies and autoimmune diseases has been introduced more frequently than before, PCP has attracted more attention. Therefore primaquine should be approved for appropriate use without delay in Japan.

  13. The therapy of kidney cancer with biomolecular drugs.

    Science.gov (United States)

    Di Lorenzo, G; Buonerba, C; Biglietto, M; Scognamiglio, F; Chiurazzi, B; Riccardi, F; Cartenì, G

    2010-11-01

    Over the last few years, targeted agents have assumed a predominant role in treatment of metastatic renal cell carcinoma (mRCC). Our aim is to discuss recent developments on this rapidly evolving topic. Sunitinib represents front-line standard treatment for the good- and intermediate prognosis groups of patients with clear cell renal carcinoma. Bevacizumab/interferon and pazopanib have also been FDA-approved as first-line agents, while sorafenib has moved toward second-line and later therapy. Temsirolimus, an mTOR inhibitor, is recommended as front line therapy for patients in the poor-risk group and is the best front-line choice for patients with non-clear cell histology. Another mTOR inhibitor, everolimus, has shown clinical benefit post-tyrosine kinasis inhibitors failure in a phase III study and is considered the standard of care in this setting. Novel prognostic and efficacy markers might help to define most appropriate therapeutic strategy. Best sequence of use of these effective agents in mRCC patients remains up to the discretion of treating physician. In light of the considerable advances in understanding the biology of mRCC, several new drugs have been recently developed, with an increasing number of treatment options. Several markers are under evaluation for diagnostic, prognostic and efficacy purposes. A treatment algorithm, based on the best scientific evidence produce so far, is presented and it will evolve as data from ongoing trials will be available. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Physical Therapy (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Physical Therapy KidsHealth / For Parents / Physical Therapy Print en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) ...

  15. Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

    Science.gov (United States)

    Joshi, Lavnish; Talat, Lazha; Yaganti, Satish; Sandhu, Sartaj; Taylor, Simon R J; Wakefield, Denis; McCluskey, Peter; Lightman, Susan

    2014-05-01

    To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  16. Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

    Science.gov (United States)

    Sadashiv, Mucheli Shravan; Rupali, Priscilla; Manesh, Abi; Kannangai, Rajesh; Abraham, Ooriapadickal Cherian; Pulimood, Susanne A; Karthik, Rajiv; Rajkumar, S; Thomas, Kurien

    2017-12-01

    Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Univariate analysis showed significant association with 1) Self-reported nonadherenceART and thus help development of targeted interventions.

  17. Second Line of Defense: Electronic Maintenance Reports, Local Maintenance Provider User Guide, Rev. 3

    Energy Technology Data Exchange (ETDEWEB)

    Leigh, Richard J.

    2012-09-01

    The Electronic Maintenance Report forms allow Local Maintenance Providers (LMP) and other program staff to enter maintenance information into a simple and secure system. This document describes the features and information required to complete the Maintenance Report forms. It is expected that all Corrective Maintenance Reports from LMPs will be submitted electronically into the SLD Portal. As an exception (e.g., when access to the SLD Portal is unavailable), Maintenance Reports can be submitted via a secure Adobe PDF form available through the Sustainability Manager assigned to each country.

  18. Second Line of Defense Megaports Initiative Sustainment Plan - Port Klang Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    King, Curtis A.

    2009-09-29

    To reduce the risk of illicit trafficking of special nuclear and other radiological materials, the Megaports Initiative installs radiation detection systems at international seaports. Port Klang, Malaysia, is one such seaport identified by the Megaports Initiative as a key area to install equipment to accomplish the mission of preventing the acquisition and smuggling of materials that could be used to create weapons of mass destruction or radiological dispersal devices. Sustainability is a critical factor of all components of the Megaports Initiative. The sustainability plan is developed to assist the partner country in securing the technical, financial, and policy commitments required to develop and implement a country-specific strategy. A robust sustainability plan will define the long-term relationship between the U.S. Department of Energy and the Government of Malaysia as well as promote the ongoing proficient radiation detection system operations at Port Klang, Malaysia.

  19. Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.

    Science.gov (United States)

    Barbot, Mattia; Trementino, Laura; Zilio, Marialuisa; Ceccato, Filippo; Albiger, Nora; Daniele, Andrea; Frigo, Anna Chiara; Mardari, Rodica; Rolma, Giuseppe; Boscaro, Marco; Arnaldi, Giorgio; Scaroni, Carla

    2016-10-01

    Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion. Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test. Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p 52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower. Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

  20. Second Line of Defense Help Desk: Electronic Maintenance Reports - Local Maintenance Provider User Guide Rev. 1

    Energy Technology Data Exchange (ETDEWEB)

    Leigh, Richard J.

    2011-12-14

    The Electronic Maintenance Report forms present a uniform dataset for analysis of Sustainability metrics. These forms collect readily minable data while allowing the attachment of site-specific checklists or other supporting files for review by the Sustainability Manager and Program Management.

  1. Second Line of Defense Megaports Initiative Sustainment Plan - Port Klang Malaysia

    International Nuclear Information System (INIS)

    King, Curtis A.

    2009-01-01

    To reduce the risk of illicit trafficking of special nuclear and other radiological materials, the Megaports Initiative installs radiation detection systems at international seaports. Port Klang, Malaysia, is one such seaport identified by the Megaports Initiative as a key area to install equipment to accomplish the mission of preventing the acquisition and smuggling of materials that could be used to create weapons of mass destruction or radiological dispersal devices. Sustainability is a critical factor of all components of the Megaports Initiative. The sustainability plan is developed to assist the partner country in securing the technical, financial, and policy commitments required to develop and implement a country-specific strategy. A robust sustainability plan will define the long-term relationship between the U.S. Department of Energy and the Government of Malaysia as well as promote the ongoing proficient radiation detection system operations at Port Klang, Malaysia.

  2. Basis of selection of first and second line highly active antiretroviral ...

    African Journals Online (AJOL)

    on genetic barrier to resistance: a literature review. Christine Katusiime1, Ponsiano Ocama2, Andrew Kambugu1. 1. Makerere University, College of Health Sciences, Infectious Diseases Institute, Kampala, Uganda. 2. Makerere University, College of Health Sciences, Department of Medicine, Kampala, Uganda. Abstract:.

  3. Decision aids for second-line palliative chemotherapy: a randomised phase II multicentre trial

    NARCIS (Netherlands)

    Oostendorp, L.J.M.; Ottevanger, P.B.; Donders, A.R.T.; Wouw, A.J. van de; Schoenaker, I.J.; Smilde, T.J.; Graaf, W.T.A. van der; Stalmeier, P.F.M.

    2017-01-01

    BACKGROUND: There is increasing recognition of the delicate balance between the modest benefits of palliative chemotherapy and the burden of treatment. Decision aids (DAs) can potentially help patients with advanced cancer with these difficult treatment decisions, but providing detailed information

  4. [Gestalt therapy.].

    Science.gov (United States)

    Corbeil, J; Poupard, D

    1978-01-01

    The authors describe Gestalt Therapy. They retrace its fundamental theoretical axes. These are psychoanalysis, character analysis, the german Gestalt theory of perception, existentialism, and the Orient. Some principal concepts are then elaborated more fully such as the cycle of awareness, desensitization, excitation anxiety and the five defense mechanisms: retroflection, introjection, projection, deflection, and confluence. The nature and goals of the therapeutic process are also described before the presentation of some techniques specific to this approach such as enactment and role playing. Finally, certain basic Gestalt rules, which aim at facilitating and intensifying the communication process among group members, are enunciated.

  5. Tibial nerve stimulation for overactive bladder syndrome unresponsive to medical therapy.

    Science.gov (United States)

    Ridout, A E; Yoong, W

    2010-02-01

    Overactive bladder syndrome is defined as a symptom syndrome which includes urinary urgency, with or without urge incontinence, usually accompanied by frequency (>8 micturitions/24 h) and nocturia. Conservative treatment usually comprises behavioural techniques, bladder retraining, pelvic floor re-education and pharmacotherapy but up to 30% of patients will remain refractory to treatment. Although second-line treatment options such as sacral nerve stimulation and intravesical botulinum A injections are valuable additions to the therapeutic arsenal, they are relatively invasive and can have serious side-effects. Inhibition of detrusor activity by peripheral neuromodulation of the posterior tibial nerve was first described in 1983, with recent authors further confirming a 60-80% positive response rate. This review was undertaken to examine published literature on percutaneous tibial nerve stimulation and to discuss outcome measures, maintenance therapy and prognostic factors of this technique.

  6. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  7. A Decision Support Tool for Appropriate Glucose-Lowering Therapy in Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Ampudia-Blasco, F Javier; Benhamou, Pierre Yves; Charpentier, Guillaume

    2014-01-01

    Abstract Background: Optimal glucose-lowering therapy in type 2 diabetes mellitus requires a patient-specific approach. Although a good framework, current guidelines are insufficiently detailed to address the different phenotypes and individual needs of patients seen in daily practice. We developed...... a patient-specific decision support tool based on a systematic analysis of expert opinion. Materials and Methods: Based on the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) 2012 position statement, a panel of 12 European experts rated the appropriateness (RAND....... The panel recommendations were embedded in an online decision support tool (DiaScope(®); Novo Nordisk Health Care AG, Zürich, Switzerland). Results: Treatment appropriateness was associated with (combinations of) the patient variables mentioned above. As second-line agents, dipeptidyl peptidase-4 inhibitors...

  8. Castration-resistant prostate cancer: systemic therapy in 2012

    Directory of Open Access Journals (Sweden)

    Fernando C. Maluf

    2012-01-01

    Full Text Available Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.

  9. Radiation therapy

    International Nuclear Information System (INIS)

    Bader, J.L.; Glatstein, E.

    1987-01-01

    The radiation oncologist encounters the critically ill immunosuppressed patient in four settings. First, the newly diagnosed cancer patient presents for initial evaluation and treatment, with immunosuppression from the cancer itself, malnutrition, concomitant infectious disease, prior drug or alcohol abuse or other medical problems. Second, the previously treated cancer patient presents with metastatic or recurrent primary cancer causing local symptoms. Immune dysfunction in this setting may be due to prior chemotherapy and/or radiation as well as any of the original factors. Third, the patient previously treated with radiation presents with a life-threatening problem possibly due to complications of prior therapy. In this setting, the radiation oncologist is asked to evaluate the clinical problem and to suggest whether radiation might be causing part or all of the problem and what can be done to treat these sequelae of radiation. Fourth, the patient with a benign diagnosis (not cancer) is seen with a problem potentially emeliorated by radiation (e.g., kidney transplant rejection, preparation for transplant, or intractable rheumatoid arthritis). This chapter reviews these four issues and presents clinical and radiobiologic principles on which recommendations for therapy are based

  10. The cost of antiretroviral therapy in Haiti

    Directory of Open Access Journals (Sweden)

    Fitzgerald Daniel W

    2008-02-01

    Full Text Available Abstract Background We determined direct medical costs, overhead costs, societal costs, and personnel requirements for the provision of antiretroviral therapy (ART to patients with AIDS in Haiti. Methods We examined data from 218 treatment-naïve adults who were consecutively initiated on ART at the GHESKIO Center in Port-au-Prince, Haiti between December 23, 2003 and May 20, 2004 and calculated costs and personnel requirements for the first year of ART. Results The mean total cost of treatment per patient was $US 982 including $US 846 in direct costs, $US 114 for overhead, and $US 22 for societal costs. The direct cost per patient included generic ART medications $US 355, lab tests $US 130, nutrition $US 117, hospitalizations $US 62, pre-ART evaluation $US 58, labor $US 51, non-ART medications $US 39, outside referrals $US 31, and telephone cards for patient retention $US 3. Higher treatment costs were associated with hospitalization, change in ART regimen, TB treatment, and survival for one year. We estimate that 1.5 doctors and 2.5 nurses are required to treat 1000 patients in the first year after initiating ART. Conclusion Initial ART treatment in Haiti costs approximately $US 1,000 per patient per year. With generic first-line antiretroviral drugs, only 36% of the cost is for medications. Patients who change regimens are significantly more expensive to treat, highlighting the need for less-expensive second-line drugs. There may be sufficient health care personnel to treat all HIV-infected patients in urban areas of Haiti, but not in rural areas. New models of HIV care are needed for rural areas using assistant medical officers and community health workers.

  11. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    Directory of Open Access Journals (Sweden)

    Kaichun Li

    2016-01-01

    Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

  12. Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review.

    Science.gov (United States)

    Chen, Li-Tzong; Oh, Do-Youn; Ryu, Min-Hee; Yeh, Kun-Huei; Yeo, Winnie; Carlesi, Roberto; Cheng, Rebecca; Kim, Jongseok; Orlando, Mauro; Kang, Yoon-Koo

    2017-10-01

    Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

  13. Targeted therapies for locally advanced or metastatic squamous cell carcinoma of the lung.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2013-12-01

    Most patients with squamous cell carcinoma (SCC) present with advanced or metastatic disease at the time of diagnosis. Given the low prevalence of oncogenic driver mutations in SCC, I do not routinely perform molecular testing. The times that I perform molecular testing in SCC are for patients with SCC and a light or never smoking history, adenosquamous histology, or when the histological diagnosis is not definitive. For patients with a good performance status and adequate organ function, a platinum doublet is the standard therapy, and I generally use carboplatin and gemcitabine or carboplatin and paclitaxel. In the second-line setting for patients who are chemotherapy candidates, I will use docetaxel on a weekly or every three week schedule. Erlotinib is a treatment option in the third-line setting. My preference is for patients to participate in clinical trials because the development of novel therapies for patients with SCC has been slow compared with nonsquamous non-small cell lung cancer. Ongoing investigations into the genomics of SCC will hopefully identify driver mutations or alterations in pathways essential for oncogenesis and tumor growth and will lead to the development of targeted therapies. The complexity of the genomics of SCC will make the development of targeted therapies challenging.

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

    Directory of Open Access Journals (Sweden)

    Bacha Tigist

    2012-08-01

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

  15. [Dysphagia in a young woman from Somalia].

    Science.gov (United States)

    Veldhuis, Suzanne; van Altena, Richard; van Steenwijk, Reindert P; Rauws, Erik A J; Eeftinck Schattenkerk, Jan Karel M

    2013-01-01

    Multidrug-resistant tuberculosis is increasing worldwide. The determination of possible resistance is essential for adequate treatment. Tuberculosis is common amongst immigrants from Somalia and extra-pulmonary localisation is often seen. A 21-year-old woman from Somalia presented with progressive dysphagia and severe weight loss. Endoscopy revealed two ulcers in the mid-oesophagus. A chest x-ray showed enlarged lymph nodes in the right hilar and mediastinal regions. The Ziehl-Neelsen stain and PCR for mycobacteria were negative. Sputum samples and oesophageal biopsies were cultured. Quadruple tuberculostatic therapy was started empirically. After five weeks, a sputum culture grew Mycobacterium tuberculosis, which was resistant to rifampicin and isoniazid. She was treated with second-line anti-tuberculous therapy and eventually recovered. Tuberculosis can manifest in many ways. It is important to obtain patient material for culture; not only to confirm the diagnosis but also for the determination of possible resistance which is necessary for adequate therapy.

  16. Dystonia: Physical Therapy

    Science.gov (United States)

    ... Online Support Frequently Asked Questions Faces of Dystonia Physical Therapy Physical therapy may be an important component of treating ... everyday tasks, Since dystonia is a neurological disorder, physical therapy does not treat the dystonia directly but ...

  17. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  18. Laser therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  19. American Music Therapy Association

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will ...

  20. [Physical therapy].

    Science.gov (United States)

    Chohnabayashi, Naohiko

    2008-01-01

    Recently, pulmonary rehabilitation program is widely considered one of the most effective and evidence-based treatment for not only chronic obstructive pulmonary disease (COPD) but many clinical situations including neuro-muscular disease, post-operative status and weaning period from the ventilator, etc. The essential components of a pulmonary rehabilitation program are team assessment, patient training, psycho-social intervention, exercise, and follow-up. In 2003, Japanese medical societies (J. Thoracic Society, J. Pul. Rehabilitation Society and J. Physiotherapist Society) made a new guideline for pulmonary rehabilitation, especially how to aproach the execise training. As for the duration after surgical operation, airway cleaning is the important technique to prevent post-operative complications including pneumonia. Postural dranage technique is well known for such condition, at the same time, several instruments (flutter vulve, positive expiratory mask, high frequecy oscillation, etc) were also used for the patient to expectrate airway mucus easier. Lung transplantation is a new method of treatment for the critically-ill patients with chronic respiratoy failure. Several techniques of physical therapy are must be needed before and after lung transplantation to prevent both pulmonary infection and osteoporosis.

  1. 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.

  2. Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

    Science.gov (United States)

    Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

    2015-01-01

    In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

  3. Complementary and Integrative Therapies

    Science.gov (United States)

    ... include: • Acupressure and acupuncture • Aromatherapy • Art therapy and music therapy • Chiropractic medicine and massage • Guided imagery • Meditation and ... should I avoid? • Is this complementary therapy (name therapy) safe? Is there research showing it is safe? • Are there side effects ...

  4. Radiotechnologies and gene therapy

    International Nuclear Information System (INIS)

    Xia Jinsong

    2001-01-01

    Gene therapy is an exciting frontier in medicine today. Radiologist will make an uniquely contribution to these exciting new technologies at every level by choosing sites for targeting therapy, perfecting and establishing routes of delivery, developing imaging strategies to monitor therapy and assess gene expression, developing radiotherapeutic used of gene therapy

  5. [Physical therapy for scars].

    Science.gov (United States)

    Masanovic, Marguerite Guillot

    2013-01-01

    Physical therapy consists notably of hand or mechanical massages, pressure therapy using various fabrics or splints, cryotherapy, laser therapy, etc. It forms part of the range of therapies used to treat pathological scars, including medical and surgical treatment. While the results are often satisfactory for hypertrophic scars, they remain uncertain for major keloids.

  6. 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

  7. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations

    Directory of Open Access Journals (Sweden)

    Aurelio Lopez

    2015-01-01

    Full Text Available We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients and more aggressive forms of disease (32 patients were the most common patterns of relapse. After second-line therapy, 75 (51.7% patients achieved at partial response and 16 (11% complete response (CR. Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037, in patients achieving CR (28.3 vs. 14.8 months; P=0.04, and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007.

  8. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations☆

    Science.gov (United States)

    Lopez, Aurelio; Mateos, Maria-Victoria; Oriol, Albert; Valero, Marta; Martínez, Joaquín; Lorenzo, Jose Ignacio; Perez, Montserrat; Martinez, Rafael; de Paz, Raquel; Granell, Miguel; De Arriba, Felipe; Blanchard, M. Jesús; Peñalver, Francisco Javier; Bello, Jose Luis; Martin, Maria Luisa; Bargay, Joan; Blade, Joan; Lahuerta, Juan Jose; San Miguel, Jesús F.; de la Rubia, Javier

    2015-01-01

    We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007). PMID:26500850

  9. A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma.

    Science.gov (United States)

    Stenner, Frank; Chastonay, Rahel; Liewen, Heike; Haile, Sarah R; Cathomas, Richard; Rothermundt, Christian; Siciliano, Raffaele D; Stoll, Susanna; Knuth, Alexander; Buchler, Tomas; Porta, Camillo; Renner, Christoph; Samaras, Panagiotis

    2012-01-01

    To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer. We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression. In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003). The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use. Copyright © 2012 S. Karger AG, Basel.

  10. Cost effectiveness analysis of clinically driven versus routine laboratory monitoring of antiretroviral therapy in Uganda and Zimbabwe.

    Directory of Open Access Journals (Sweden)

    Antonieta Medina Lara

    Full Text Available Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART have rarely been evaluated.Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779. Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM or laboratory and clinical monitoring (LCM; individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial.3316 (1660LCM;1656CDM symptomatic, immunosuppressed ART-naive adults (median (IQR age 37 (32,42; CD4 86 (31,139 cells/mm(3 were followed for median 4.9 years. LCM had a mean 0.112 year (41 days survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks. CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term.There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring

  11. Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability

    Directory of Open Access Journals (Sweden)

    Kimmel April D

    2012-09-01

    Full Text Available Abstract Background In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods In settings with two available ART regimens, we assessed two strategies: (1 continue ART after second-line failure (Status Quo and (2 discontinue ART after second-line failure (Alternative. A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7% to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8% to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0% to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1% died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are

  12. Music therapy in kindergarten

    OpenAIRE

    Šírová, Michaela

    2017-01-01

    This work deals with the subject of music therapy in a special kindergarten for the children with combined disabilities. In the theoretical part it clarifies the concept and principle of music therapy and characterizes the types of disabilities that occur at researched clients. As a research method were used observation and interviews with three music therapists from the institution. KEYWORDS Music therapy, preschool education, special pedagogy, group music therapy,individual music therapy, p...

  13. Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer.

    Science.gov (United States)

    Janmaat, Vincent T; Steyerberg, Ewout W; van der Gaast, Ate; Mathijssen, Ron Hj; Bruno, Marco J; Peppelenbosch, Maikel P; Kuipers, Ernst J; Spaander, Manon Cw

    2017-11-28

    survival time was one month. Five studies in 750 participants contributed data to the comparison of palliative therapy versus best supportive care. We found a benefit in overall survival in favor of the group receiving palliative chemotherapy and/or targeted therapy compared to best supportive care (HR 0.81, 95% CI 0.71 to 0.92, high-quality evidence). Subcomparisons including only people receiving second-line therapies, chemotherapies, targeted therapies, adenocarcinomas, and squamous cell carcinomas all showed a similar benefit. The only individual agent that more than one study found to improve both overall survival and progression-free survival was ramucirumab. Palliative chemotherapy and/or targeted therapy increased the frequency of grade 3 or higher treatment-related toxicity. However, treatment-related deaths did not occur more frequently. Quality of life often improved in the arm with an additional agent. People who receive more chemotherapeutic or targeted therapeutic agents have an increased overall survival compared to people who receive less. These agents, administered as both first-line or second-line treatments, also led to better overall survival than best supportive care. With the exception of ramucirumab, it remains unclear which other individual agents cause the survival benefit. Although treatment-associated toxicities of grade 3 or more occurred more frequently in arms with an additional chemotherapy or targeted therapy agent, there is no evidence that palliative chemotherapy and/or targeted therapy decrease quality of life. Based on this meta-analysis, palliative chemotherapy and/or targeted therapy can be considered standard care for esophageal and gastroesophageal junction carcinoma.

  14. Systemic therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Andrezalova Vochyanova, I.; Salek, T.

    2012-01-01

    Pancreatic cancer is the fourth comment cause of cancer-related death in men. Most patients with pancreatic cancer are diagnosed at advanced, non-resectable stage. Late detection, early metastases, difficult surgical approached, cancer resistant to systemic chemo and radiotherapy - all contribute to its in faust prognosis. Only about 5 % of patients will live 5 years after diagnosis. Gemcitabine - based combination treatments is the standard for advanced pancreatic cancer. The combination of fluorouracil, folinic acid, irinotecan and oxaliplatin led to median survival of 11 months. No standard second-line treatment exists for pancreatic cancer. (author)

  15. Pemetrexed With Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Stinchcombe, Thomas E; Borghaei, Hossein; Barker, Scott S; Treat, Joseph Anthony; Obasaju, Coleman

    2016-01-01

    Standard platinum-based chemotherapy combinations for advanced non-small-cell lung cancer (NSCLC) have reached a plateau in terms of the survival benefit they offer for patients. In addition, the emerging clinical trend of tailored treatment based on patient characteristics has led to the development of therapeutic strategies that target specific cancer-related molecular pathways, including epidermal growth factor receptor (EGFR), angiogenesis, and anaplastic lymphoma kinase inhibitors. Current research is focused on combining targeted therapy with platinum-based chemotherapy in an endeavor to achieve an additional benefit in specific patient populations. Currently, pemetrexed is indicated for use in the first-line, maintenance, and second-line settings for the treatment of nonsquamous NSCLC. The combination of pemetrexed and cisplatin is well tolerated and is the approved standard first-line therapy. Thus, the pemetrexed-platinum backbone provides an attractive option for combination with targeted therapies. This review aims to summarize the current knowledge and future prospects of the use of pemetrexed-platinum as a backbone for combination with targeted therapies for NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  17. The Scope of Practice of Occupational Therapy in U.S. Criminal Justice Settings.

    Science.gov (United States)

    Muñoz, Jaime P; Moreton, Emily M; Sitterly, Audra M

    2016-09-01

    In the past 40 years, prison populations in the U.S. have nearly quadrupled while funding for rehabilitation, education and other programmes has been cut. Despite accounting for a small fraction of the world's population more than 20% of the worlds incarcerated population is in the U.S. and the rate of recidivism remains alarmingly high. Occupational therapists have the capability to play a significant role in addressing the needs of persons within the criminal justice system. However, the profession has been slow to delineate of the role occupational therapy within criminal justice settings. This study sought to provide a descriptive analysis of current occupational therapy roles and practices within the U.S. criminal justice system. Using survey research methods, the researchers collected data from respondents (N = 45; Response Rate + 51.7%) to establish a baseline of the scope of practices employed by occupational therapists working in the U.S. criminal justice system. U.S. practitioners work within institutional and community based criminal justice settings. Primary practice models, assessments and group interventions were catalogued. Respondents strongly valued the creation of networking to build the professions' presence within criminal justice settings. Occupational therapy in the criminal justice system remains an emerging practice arena. Understanding the current scope of practice in the U.S. and creating a mechanism for collaboration may help increase the depth, breadth and overall growth of the profession's role in these settings. The sampling method does not guarantee a representative sample of the population and is limited to practice within the United States. Survey design may not have allowed for respondents to fully describe their practice experiences. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  18. MOSFET dosimetry of the radiation therapy microbeams at the European synchrotron radiation facility

    International Nuclear Information System (INIS)

    Rozenfeld, A.; Lerch, M.

    2002-01-01

    Full text: We have developed an innovative on-line MOSFET readout system for use in the quality assurance of radiation treatment beams. Recently the system has found application in areas where excellent spatial resolution is also a requirement in the quality assurance process, for example IMRT, and microbeam radiation therapy. The excellent spatial resolution is achieved by using a quadruple RADFET TM chip in 'edge on' mode. In developing this approach we have found that the system can be utilised to determine any error in the beam profile measurements due to misalignment of RADFET with respect to the radiation beam or microbeam. Using this approach will ensure that the excellent spatial resolution of the RADFET used in 'edge-on' mode is fully utilised. In this work we report on dosimetry measurements performed at the microbeam radiation therapy beamline located at the European Synchrotron Radiation Facility. The synchrotron planar array microbeam with size 10-30 μm and pitch ∼200 μm has found an important application in microbeam radiation therapy (MRT) of brain tumours in infants for whom other kinds of radiotherapy are inadequate and/or unsafe. The radiation damage from an array of parallel microbeams correlates strongly with the range of peak-valley dose ratios (PVDR), ie, the range of the ratio of the absorbed dose to tissue directly in line with the mid-plane of the microbeam to that in the mid-plane between adjacent microbeams. Novel physical dosimetry of the microbeams using the online MOSFET reader system will be presented. Comparison of the experimental results with both GaF film measurements and Monte Carlo computer-simulated dosimetry are described here for selected points in the peak and valley regions of a microbeam-irradiated tissue phantom

  19. Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy.

    Science.gov (United States)

    Matsumoto, Kazumasa; Mochizuki, Kohei; Hirayama, Takahiro; Ikeda, Masaomi; Nishi, Morihiro; Tabata, Ken-ichi; Okazaki, Miyoko; Fujita, Tetsuo; Taoka, Yoshinori; Iwamura, Masatsugu

    2015-01-01

    This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine 1,000 mg/m2 on days 1, 8 and 15 and nedaplatin 70 mg/m2 on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.

  20. IL-17 for therapy.

    Science.gov (United States)

    Kurschus, Florian C; Moos, Sonja

    2017-09-01

    The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis. Interestingly, this model showed some typical comorbidities found in humans with psoriasis. In this review, we will discuss why IL-17 is a good target especially in psoriasis and what we learned from mouse models about its functions in pathological situations. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  1. Adlerian Marriage Therapy.

    Science.gov (United States)

    Carlson, Jon; Dinkmeyer, Don, Sr.

    1987-01-01

    Describes the assumptions, processes, and techniques used in Alderian marriage therapy. Describes purpose of therapy as assessing current beliefs and behaviors while educating the couple in new procedures that can help the couple establish new goals. (Author/ABL)

  2. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  3. Complementary Pancreatitis Therapies

    Science.gov (United States)

    ... medication, and improve quality of life.1,2 Massage Therapy Massage therapy involves touch and different techniques of stroking ... of the body or be a full-body massage. Massage can be performed through one’s clothing or ...

  4. [Play therapy in hospital].

    Science.gov (United States)

    Gold, Katharina; Grothues, Dirk; Leitzmann, Michael; Gruber, Hans; Melter, Michael

    2012-01-01

    The following article presents an overview of current research studies on play therapy in the hospital. It highlights individual diagnoses for which play therapy has shown reasonable success. The aim of this review is to describe the current status of the scientific debate on play therapy for sick children in order to allow conclusions regarding the indications for which play therapy is or might be useful.

  5. Tumor therapy and pregnancy

    International Nuclear Information System (INIS)

    Joss, R.; Brunner, K.W.

    1982-01-01

    Many successfully treated tumour patients are children and juveniles. This raises questions as to the effects of tumour therapy on reproductiveness and offspring. The possible extent of damage to the male and female gonads caused by surgical, chemical, and radiological tumour therapy is investigated. Also, the problem of tumour therapy or women developing neoplasms during pregnancy. Pregnancies after successful tumour therapy are quite frequent today. Experience so far suggests that the rate of congenital deformities is not significantly increased. (orig.) [de

  6. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

  7. Play Therapy: A Review

    Science.gov (United States)

    Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

    2009-01-01

    This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…

  8. Evaluation of Inter Therapy

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This article (revised conference lecture from the 10th World Congress of Music Therapy, Oxford July 2002)) emphasizes the evaluation of the training of Inter Therapy for music therapy students at the MA training at Aalborg University. The students take turns in being client and therapist within...

  9. Music Therapy for Seniors

    OpenAIRE

    SLUNEČKOVÁ, Petra

    2014-01-01

    This bachelor thesis deals with the use of music therapy in the lives of seniors. The target of this thesis is to map the possibilities of using music therapy ways with seniors and to recommend a suitable music therapy resources on the basis of the research and evaluation of obtained dates. The theoretical part describes the term "the music therapy", e.g. concept, definition, types and forms, the development of music therapy, the history, methods and techniques. This age group is defined in t...

  10. Inhalation Therapy in Horses.

    Science.gov (United States)

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. 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.

  12. [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.

  13. Radiation recall dermatitis with soft tissue necrosis following pemetrexed therapy: a case report

    Directory of Open Access Journals (Sweden)

    Spirig Christian

    2009-11-01

    Full Text Available Abstract Introduction Radiation recall dermatitis is a well known but still poorly understood inflammatory reaction. It can develop in previously irradiated areas and has been shown to be triggered by a variety of different drugs, including cytostatic agents. Pemetrexed may cause radiation recall dermatitis in pre-irradiated patients. Case presentation We present the case of a 49-year-old Caucasian woman with non-small cell lung cancer who was initially treated with carboplatin and paclitaxel concomitant with radiotherapy after suffering a painful plexus brachialis infiltration. Due to disease progression, a second-line treatment with pemetrexed was started. A severe soft tissue necrosis developed despite steroid treatment and plastic surgery. Conclusion To the best of our knowledge, we present the first case of a patient with severe soft tissue necrosis in a pre-irradiated area after pemetrexed therapy. We believe that physicians treating patients with pemetrexed should be aware of the severe, possibly life-threatening effects that may be induced by pemetrexed after previous radiation therapy.

  14. [Music therapy and depression].

    Science.gov (United States)

    Van Assche, E; De Backer, J; Vermote, R

    2015-01-01

    Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy.

  15. Hendee's radiation therapy physics

    CERN Document Server

    Pawlicki, Todd; Starkschall, George

    2016-01-01

    The publication of this fourth edition, more than ten years on from the publication of Radiation Therapy Physics third edition, provides a comprehensive and valuable update to the educational offerings in this field. Led by a new team of highly esteemed authors, building on Dr Hendee’s tradition, Hendee’s Radiation Therapy Physics offers a succinctly written, fully modernised update. Radiation physics has undergone many changes in the past ten years: intensity-modulated radiation therapy (IMRT) has become a routine method of radiation treatment delivery, digital imaging has replaced film-screen imaging for localization and verification, image-guided radiation therapy (IGRT) is frequently used, in many centers proton therapy has become a viable mode of radiation therapy, new approaches have been introduced to radiation therapy quality assurance and safety that focus more on process analysis rather than specific performance testing, and the explosion in patient-and machine-related data has necessitated an ...

  16. Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.

    Science.gov (United States)

    Giuffrida, Gaetano; Lombardo, Rita; Di Francesco, Ernesto; Parrinello, Laura; Di Raimondo, Francesco; Fiumara, Agata

    2016-11-08

    Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no

  17. Radon therapy; Radon in der Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Spruck, Kaija [Technische Hochschule Mittelhessen, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

    2017-04-01

    Radon therapies are used since more than 100 years in human medicine. Today this method is controversially discussed due to the possible increase of ionizing radiation induced tumor risk. Although the exact mode of biological radiation effect on the cell level is still not known new studies show the efficiency of the radon therapy without side effect for instance for rheumatic/inflammatory or respiratory disorders.

  18. Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease.

    Science.gov (United States)

    Lim, Joo Hyun; Kim, Sang Gyun; Song, Ji Hyun; Hwang, Jae Jin; Lee, Dong Ho; Han, Jae Pil; Hong, Su Jin; Kim, Ji Hyun; Jeon, Seong Woo; Kim, Gwang Ha; Shim, Ki-Nam; Shin, Woon Geon; Kim, Tae Ho; Kim, Sun Moon; Chung, Il-Kwon; Kim, Hyun-Soo; Kim, Heung Up; Lee, Joongyub; Kim, Jae Gyu

    2017-03-15

    The resistance rate of Helicobacter pylori is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H. pylori eradication in peptic ulcer disease. Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line H. pylori eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed. The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655). Levofloxacin-based third-line H. pylori eradication showed efficacy similar to that of previously reported first/second-line therapies.

  19. A prospective, open-label study of low-dose total skin electron beam therapy in mycosis fungoides

    DEFF Research Database (Denmark)

    Kamstrup, Maria R; Specht, Lena; Skovgaard, Gunhild L

    2008-01-01

    causes and did not complete treatment. Acute side effects included desquamation, xerosis, and erythema of the skin. No severe side effects were observed. CONCLUSION: Low-dose total skin electron beam therapy can induce complete and partial responses in Stage IB-II mycosis fungoides; however, the duration......PURPOSE: To determine the effect of low-dose (4 Gy) total skin electron beam therapy as a second-line treatment of Stage IB-II mycosis fungoides in a prospective, open-label study. METHODS AND MATERIALS: Ten patients (6 men, 4 women, average age 68.7 years [range, 55-82 years......]) with histopathologically confirmed mycosis fungoides T2-T4 N0-N1 M0 who did not achieve complete remission or relapsed within 4 months after treatment with psoralen plus ultraviolet-A were included. Treatment consisted of low-dose total skin electron beam therapy administered at a total skin dose of 4 Gy given in 4...

  20. 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...

  1. Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

    Directory of Open Access Journals (Sweden)

    Vaishali Kolgiri Honnapurmath

    2017-01-01

    Full Text Available Background and Objectives: Insulin resistance (IR is frequent in human immunodeficiency virus (HIV infection and may be related to antiretroviral therapy (ART. Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG, as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group (n = 300, HIV-positive without ART (n = 100, HIV-positive with ART first line (n = 100, and HIV-positive with ART second line (n = 100. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509 P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

  2. 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.

  3. 75 FR 50880 - TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech Therapy

    Science.gov (United States)

    2010-08-18

    ... 0720-AB36 TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech... referrals of beneficiaries to the Military Health System for physical therapy, occupational therapy, and... practitioners will be allowed to issue referrals to patients for physical therapy, occupational therapy, and...

  4. [Anti-N-methyl-D aspartate receptor encephalitis - guideline to the challenges of diagnosis and therapy].

    Science.gov (United States)

    Hau, Lídia; Csábi, Györgyi; Tényi, Tamás

    2015-01-01

    Anti-N-methyl-D-Aspartate encephalitis is a recently diagnosed autoimmune disorder with increasing significance. During this disease antibodies are produced against the subunit of the NMDA receptor, which cause different symptoms, both psychiatric and neurological. The aim of this publication is to introduce this disease, to facilitate the diagnosis and to recommend therapeutical guideline. In this review we summarized the relevant literature published between 2007 and 2015 giving emphasis on etiopathogenesis, diagnosis, differential diagnosis, treatment and prognosis. In the etiology an underlying tumor or a viral agent should be considered. During the disease we can discern 3 periods: first prodromal viral infections-like symptoms can be seen, 1-2 weeks later psychiatric symptoms, such as aggression, sleep and behavior disturbances appear. After that neurological symptoms (tonic-clonic convulsions, aphasia, catatonia, orofacial dyskinesia, autonom lability, altered mental state) are typical, and the patient's condition deteriorates. For the correct diagnosis it is necessary to detect antibodies against the NMDA receptor from the serum and the liquor. Steroids, immunoglobulins and plasmaheresis are the first-line therapies. If the disease is unresponsive, then as a second-line therapy anti-CD 20 (Rituximab) and cyclophosphamid can be useful. Most of the patients are improving without any neurological sequale with prompt detection and appropriate therapy. It is important to be familiar with the symptoms, diagnosis and therapy of this disease as a practicing clinician, especially as a psychiatrist or neurologist. 75 percentage of the patients are admitted to psychiatric departments first because of the leading symptoms. Autoimmune NMDA encephalitis is a reversible disease after early diagnosis and treatment.

  5. A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria.

    Directory of Open Access Journals (Sweden)

    Charles F Gilks

    Full Text Available In low-income countries, viral load (VL monitoring of antiretroviral therapy (ART is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable.3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4<100 cells/mm(3 were reviewed in 361 LCM, 314 CDM participants who switched over median 5 years follow-up. Retrospective VLs were available in 368 (55% participants.Overall, 265/361 (73% LCM participants failed with CD4<100 cells/mm(3; only 7 (2% switched with CD4≥250 cells/mm(3, four switches triggered by WHO events. Without CD4 monitoring, 207/314 (66% CDM participants failed with WHO 4 events, and 77(25%/30(10% with single/multiple WHO 3 events. Failure/switching with single WHO 3 events was more likely with CD4≥250 cells/mm(3 (28/77; 36% (p = 0.0002. CD4 monitoring reduced switching with viral suppression: 23/187 (12% LCM versus 49/181 (27% CDM had VL<400 copies/ml at failure/switch (p<0.0001. Amongst CDM participants with CD4<250 cells/mm(3 only 11/133 (8% had VL<400 copies/ml, compared with 38/48 (79% with CD4≥250 cells/mm(3 (p<0.0001.Multiple, but not single, WHO 3 events predicted first-line ART failure. A CD4 threshold 'tiebreaker' of ≥250 cells/mm(3 for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 'clinical failures' would particularly avoid premature, costly

  6. 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.

  7. [Therapy of intermediate uveitis].

    Science.gov (United States)

    Doycheva, D; Deuter, C; Zierhut, M

    2014-12-01

    Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.

  8. Fertility and cancer therapy

    International Nuclear Information System (INIS)

    Maguire, L.C.

    1979-01-01

    With increased survival of increasing numbers of cancer patients as a result of therapy, the consequences, early and late, of the therapies must be realized. It is the treating physician's duty to preserve as much reproductive potential as possible for patients, consistent with adequate care. With radiotherapy this means shielding the gonads as much as possible, optimal but not excessive doses and fields, oophoropexy, or sperm collection and storage prior to irradiation. With chemotherapy it means the shortest exposure to drugs consistent with best treatment and prior to therapy the collection and storage of sperm where facilities are available. At present this is still an experimental procedure. Artificial insemination for a couple when the male has received cancer therapy is another alternative. Finally, it is the responsibility of physicians caring for patients with neoplasms to be knowledgeable about these and all other effects of therapy so that patients may be counseled appropriately and understand the implications of therapy for their life

  9. Genetically Guided Statin Therapy

    Science.gov (United States)

    2017-03-01

    number of new statin prescriptions, and (4) patient reported quality of life, physical activity, perceptions regarding statin therapy , and pain as...outcomes known to be prevented by statin therapy , we examined hospitalizations for three diagnoses: acute myocardial infarction (MI), stroke, and...cholesterol. However, the ultimate goal of statin therapy is to decrease incidence of CAD, acute myocardial infarction and perhaps stroke. However, there is a

  10. Nuclear medicine therapy

    CERN Document Server

    Eary, Janet F

    2013-01-01

    One in three of the 30 million Americans who are hospitalized are diagnosed or treated with nuclear medicine techniques. This text provides a succinct overview and detailed set of procedures and considerations for patient therapy with unsealed radioactivity sources.  Serving as a complete literature reference for therapy with radiopharmaceuticals currently utilized in practice, this source covers the role of the physician in radionuclide therapy, and essential procedures and protocols required by health care personnel.

  11. Population-based surveillance of HIV drug resistance emerging on treatment and associated factors at sentinel antiretroviral therapy sites in Namibia.

    Science.gov (United States)

    Hong, Steven Y; Jonas, Anna; DeKlerk, Michael; Shiningavamwe, Andreas; Desta, Tiruneh; Badi, Alfons; Morris, Lynn; Hunt, Gillian M; Ledwaba, Johanna; Sheehan, Heidi B; Lau, Kiger; Trotter, Andrew; Tang, Alice M; Wanke, Christine; Jordan, Michael R

    2015-04-01

    The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors. Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR). Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021). Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.

  12. American Physical Therapy Association

    Science.gov (United States)

    ... Do APTA represents more than 100,000 members: physical therapists, physical therapist assistants, and students of physical therapy. Other Popular Resources: - Member Directory - Annual Reports ...

  13. Is Bicarbonate Therapy Useful?

    Science.gov (United States)

    Hopper, Kate

    2017-03-01

    Despite concerns about the negative effects of metabolic acidosis, there is minimal evidence that sodium bicarbonate administration is an effective treatment. In addition, sodium bicarbonate therapy is associated with many adverse effects, including paradoxic intracellular acidosis, hypokalemia, hypocalcemia, hypernatremia, and hyperosmolality. Definitive recommendations regarding bicarbonate therapy are challenging as there is little high-quality evidence available. In most clinical scenarios of metabolic acidosis, treatment efforts should focus on resolution of the underlying cause, and sodium bicarbonate therapy should be used with caution, if at all. An exception to this is kidney disease, wherein sodium bicarbonate therapy may have a valuable role. Published by Elsevier Inc.

  14. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Ninan, Neethu

    2012-01-01

    Nanotechnology has the power to radically change the way cancer is diagnosed, imaged, and treated. The holistic approach to cancer involves noninvasive procedures that emphasize restoring the health of human energy fields. Presenting a wealth of information and research about the most potent cancer healing therapies, this forward-thinking book explores how nanomedicine, holistic medicine, and other cancer therapies play important roles in treatment of this disease. Topics include nanobiotechnology for antibacterial therapy and diagnosis, mitochondrial dysfunction and cancer, antioxidants and combinatorial therapies, and optical and mechanical investigations of nanostructures for biomolecular detection.

  15. Medical Art Therapy

    Directory of Open Access Journals (Sweden)

    Birgul Aydin

    2012-03-01

    Full Text Available Art therapy is a form of expressive therapy that uses art materials. Art therapy combines traditional psychotherapeutic theories and techniques with an understanding of the psychological aspects of the creative process, especially the affective properties of the different art materials. Medical art therapy has been defined as the clinical application of art expression and imagery with individuals who are physically ill, experiencing physical trauma or undergoing invasive or aggressive medical procedures such as surgery or chemotherapy and is considered as a form of complementary or integrative medicine. Several studies have shown that patients with physical illness benefit from medical art therapy in different aspects. Unlike other therapies, art therapy can take the patients away from their illness for a while by means of creative activities during sessions, can make them forget the illness or lost abilities. Art therapy leads to re-experiencing normality and personal power even with short creative activity sessions. In this article definition, influence and necessity of medical art therapy are briefly reviewed.

  16. Biological therapies for spondyloarthritis.

    Science.gov (United States)

    Bruner, Vincenzo; Atteno, Mariangela; Spanò, Angelo; Scarpa, Raffaele; Peluso, Rosario

    2014-06-01

    Biological therapies and new imaging techniques have changed the therapeutic and diagnostic approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α (TNFα) inhibitor treatment is currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) has failed. TNFα inhibitor treatment is more effective in preventing articular damage in peripheral joints than in axial ones. It is important to treat patients at an early stage of disease to reduce disease progression; moreover it is necessary to identify causes of therapy inefficacy in preventing joint damage in the axial subset.

  17. Neutron Therapy Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Neutron Therapy Facility provides a moderate intensity, broad energy spectrum neutron beam that can be used for short term irradiations for radiobiology (cells)...

  18. PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients: Dramatic improvement of prognosis and overall survival after decades of hopelessness in patients with metastatic urothelial cancer.

    Science.gov (United States)

    Resch, Irene; Shariat, Shahrokh F; Gust, Kilian M

    2018-01-01

    Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.

  19. Therapy with radionuclides. Radionuklid-Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Hotze, A.L. (Bonn Univ. (Germany). Klinik fuer Nuklearmedizin)

    1992-12-01

    Radioiodine therapy of benign and malignant thyroid diseases is a well-established procedure in Nuclear Medicine. However, the therapeutic use of radioisotopes in other diseases is relatively unknown among our refering physicians. The therapeutic effects of intraarticular (rheumatoid arthritis) and intracavitary (pleural and peritoneal carcinosis) applications yields good results. The radiophosphorus therapy in polycythemia vera rubra has always to be considered as an alternative to chemotherapy. The use of analgetics may be reduced by pain therapy of bone metastasis by injection of bone-seeking beta emitters like Rh-186 HEDP. Other procedures like therapeutic application of meta-iodo-benzylguanidine in neuroblastoma and malignant pheochromocytoma resulted in at least remissions of the disease. Radioimmunotherapy needs further evaluation before it can be recommended as a routine procedure. (orig.).

  20. Gene therapy and radionuclides targeting therapy in mammary carcinoma

    International Nuclear Information System (INIS)

    Song Jinhua

    2003-01-01

    Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

  1. History of gene therapy.

    Science.gov (United States)

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    An essential part in cancer radiotherapy, is to direct a sufficiently high dose towards the tumour, without damaging the surrounding tissue. Different techniques such as intensity modulated radiation therapy and proton therapy have been developed, in order to reduce the dose to the normal tissue...

  3. Play Therapy. ERIC Digest.

    Science.gov (United States)

    Landreth, Garry; Bratton, Sue

    Play therapy is based on developmental principles and, thus, provides, through play, developmentally appropriate means of expression and communication for children. Therefore, skill in using play therapy is an essential tool for mental health professionals who work with children. Therapeutic play allows children the opportunity to express…

  4. Therapy of Lies

    Science.gov (United States)

    Price, Sean

    2012-01-01

    Conversion therapy comes in many forms, ranging from informal chats with counselors to aggressive physical coercion, but all are based on the belief that a gay male or a lesbian can be changed "back" to heterosexual behavior. It is not just alarmed parents who turn to this therapy. Many LGBT individuals seek out such treatment in an effort to…

  5. Therapy in Motion.

    Science.gov (United States)

    Costonis, Maureen Needham, Ed.

    This book contains a collection of articles on the subject of movement therapy. It can be used as a set of supplementary readings for an academic course in dance therapy or a psychiatric residency program. It includes an exhaustive bibliography on this field for students and practioners in this field. Four principal themes have been selected as a…

  6. [Dance/Movement Therapy.

    Science.gov (United States)

    Fenichel, Emily, Ed.

    1994-01-01

    This newsletter theme issue focuses on dance, play, and movement therapy for infants and toddlers with disabilities. Individual articles are: "Join My Dance: The Unique Movement Style of Each Infant and Toddler Can Invite Communication, Expression and Intervention" (Suzi Tortora); "Dynamic Play Therapy: An Integrated Expressive Arts Approach to…

  7. Electroconvulsive Therapy and Suicide.

    Science.gov (United States)

    Tanney, Bryan L.

    1986-01-01

    When the effectiveness and mortality-morbidity of electroconvulsive therapy (ECT) are compared with those of drug therapies, it appears that ECT is an effective and preferred treatment strategy. It remains underutilized as a modality of suicide prevention. Addresses controversies that presently limit the use of this treatment. (Author/ABB)

  8. Massage Therapy Research

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

    2007-01-01

    Massage therapy has been notably effective in preventing prematurity, enhancing growth of infants, increasing attentiveness, decreasing depression and aggression, alleviating motor problems, reducing pain, and enhancing immune function. This review covers massage therapy research from the last decade, as an update to the American Psychologist 1998…

  9. Radiation Therapy - Multiple Languages

    Science.gov (United States)

    ... W XYZ List of All Topics All Radiation Therapy - Multiple Languages To use the sharing features on this page, ... Information Translations Vietnamese (Tiếng Việt) Expand Section Radiation Therapy - Tiếng Việt (Vietnamese) ... Health Information Translations Characters not displaying correctly on this page? See language display issues . Return to the MedlinePlus Health Information ...

  10. Boganmeldelse - Music Therapy Research

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2006-01-01

    . Alligevel følger her en anbefaling af bogen: for musikterapeuter er det en bog, man ikke kommer uden om. Music Therapy Research, på dansk Musikterapiforskning, er en gennemrevideret, ja faktisk nyudgivelse, af bogen Music Therapy Research: Quantitative and Qualitative Perspectives, som udkom i 1995. Også...

  11. Pediatric Music Therapy.

    Science.gov (United States)

    Lathom-Radocy, Wanda B.

    This book on music therapy includes relevant medical, psychological, and developmental information to help service providers, particularly music therapists, and parents to understand children with disabilities. The first two chapters describe the process of assessment and delineation of goals in music therapy that leads to the design of the music…

  12. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... et al. Photodynamic therapy. Journal of the National Cancer Institute 1998; 90(12):889–905. [PubMed Abstract] Gudgin Dickson EF, Goyan RL, Pottier RH. New directions in photodynamic therapy. Cellular and Molecular Biology 2002; 48(8):939–954. [PubMed Abstract] Capella ...

  13. Radiation Therapy Side Effects

    Science.gov (United States)

    Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

  14. Art Therapy: A Bibliography.

    Science.gov (United States)

    Gantt, Linda, Comp.; Schmal, Marilyn Strauss, Comp.

    The bibliography on art therapy presents 1175 citations (1940-1973) drawn from searches of the medical indexes, computer systems of the National Library of Medicine and the National Institute of Mental Health, other bibliographies, Centre International de Documentation Concernant les Expressions Plastiques, and the American Journal of Art Therapy.…

  15. Experiential Learning and Therapy.

    Science.gov (United States)

    Hatala, Elaine

    This paper describes the experiential therapy program at the Bowling Green Adolescent Center (New Jersey). This model supports the view that the therapeutic process of addiction treatment is accelerated and enhanced by providing the patients with experiential interventions. Experiential therapy includes goal setting, hands-on participation,…

  16. Activity Therapy: An Alternative Therapy for Adolescents.

    Science.gov (United States)

    Kottman, Terry T.; And Others

    1987-01-01

    Discusses the benefits of activity therapy for preteens and adolescents, where the client is engaged in nonverbal modes of relationship--games, free play, movement, drama, music, art or other activities, as the chief therapeutic media in which conflicts are resolved and intellectual and emotional energies freed. Reviews the literature, describes…

  17. Animal-Assisted Therapy and Occupational Therapy

    Science.gov (United States)

    Andreasen, Gena; Stella, Tiffany; Wilkison, Megan; Szczech Moser, Christy; Hoelzel, Allison; Hendricks, Laura

    2017-01-01

    The use of animals for therapeutic purposes has been documented in the literature for centuries. This review will highlight evidence of the benefits of animal-assisted therapy as well as provide a plethora of resources for therapists interested in learning more about how animals can provide restorative benefits for their clients.

  18. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  19. Medical therapy in acromegaly.

    LENUS (Irish Health Repository)

    Sherlock, Mark

    2011-05-01

    Acromegaly is a rare disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. The disease is associated with increased morbidity and premature mortality, but these effects can be reduced if GH levels are decreased to <2.5 μg\\/l and IGF-1 levels are normalized. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients\\' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant. Medical therapy is currently most widely used as secondary treatment for persistent or recurrent acromegaly following noncurative surgery, although it is increasingly used as primary therapy. This Review provides an overview of current and future pharmacological therapies for patients with acromegaly.

  20. Pharmacological therapy for amblyopia

    Directory of Open Access Journals (Sweden)

    Anupam Singh

    2017-01-01

    Full Text Available Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time, penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

  1. Music therapy improvisation

    Directory of Open Access Journals (Sweden)

    Mira Kuzma

    2001-09-01

    Full Text Available In this article, the technique of music therapy – music therapy improvisation is introduced. In this form of music therapy the improvising partners share meaning through the improvisation: the improvisation is not an end in itself: it portrays meaning that is personal, complex and can be shared with the partner. The therapeutic work, then, is meeting and matching the client's music in order to give the client an experience of "being known", being responded through sounds and being able to express things and communicate meaningfully. Rather than the client playing music, the therapy is about developing the engagement through sustained, joint improvisations. In music therapy, music and emotion share fundamental features: one may represent the other, i.e., we hear the music not as music but as dynamic emotional states. The concept of dynamic structure explains why music makes therapeutic sense.

  2. Accelerators for cancer therapy

    International Nuclear Information System (INIS)

    Lennox, Arlene J.

    2000-01-01

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy

  3. Music therapy in dementia

    DEFF Research Database (Denmark)

    McDermott, Orii; Crellin, Nadia; Ridder, Hanne Mette Ochsner

    2013-01-01

    Objective Recent reviews on music therapy for people with dementia have been limited to attempting to evaluate whether it is effective, but there is a need for a critical assessment of the literature to provide insight into the possible mechanisms of actions of music therapy. This systematic review......, five studies investigated hormonal and physiological changes, and five studies focused on social and relational aspects of music therapy. The musical interventions in the studies were diverse, but singing featured as an important medium for change. Conclusions Evidence for short-term improvement...... in mood and reduction in behavioural disturbance was consistent, but there were no high-quality longitudinal studies that demonstrated long-term benefits of music therapy. Future music therapy studies need to define a theoretical model, include better-focused outcome measures, and discuss how the findings...

  4. Proton therapy physics

    CERN Document Server

    2012-01-01

    Proton Therapy Physics goes beyond current books on proton therapy to provide an in-depth overview of the physics aspects of this radiation therapy modality, eliminating the need to dig through information scattered in the medical physics literature. After tracing the history of proton therapy, the book summarizes the atomic and nuclear physics background necessary for understanding proton interactions with tissue. It describes the physics of proton accelerators, the parameters of clinical proton beams, and the mechanisms to generate a conformal dose distribution in a patient. The text then covers detector systems and measuring techniques for reference dosimetry, outlines basic quality assurance and commissioning guidelines, and gives examples of Monte Carlo simulations in proton therapy. The book moves on to discussions of treatment planning for single- and multiple-field uniform doses, dose calculation concepts and algorithms, and precision and uncertainties for nonmoving and moving targets. It also exami...

  5. Pharmacological therapy for amblyopia

    Science.gov (United States)

    Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

    2017-01-01

    Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

  6. Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report

    Directory of Open Access Journals (Sweden)

    A. Despotovic

    2016-01-01

    Full Text Available Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS. The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment.

  7. [Therapy-resistant and therapy-refractory arterial hypertension].

    Science.gov (United States)

    Wallbach, M; Koziolek, M J

    2018-05-02

    Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

  8. Interest of synchrotron radiation for the therapy of brain tumors: methodology and preclinical applications; Interet du rayonnement synchrotron dans la therapie des tumeurs cerebrales: methodologie et applications precliniques

    Energy Technology Data Exchange (ETDEWEB)

    Regnard, P

    2007-12-15

    Microbeam radiation (M.R.T.) and stereotactic synchrotron radiation therapy (S.S.R.T.) are innovative techniques currently developed at the european Synchrotron radiation facility. these techniques led to promising, but rarely reproduced, results. the use of different tumoral models for each techniques limit comparisons. M.R.T. experiments on rats bearing 9L tumors 14 days after implantation displayed a double median survival time ( from 20 to 40 days) with a 200 {mu}m spacing irradiation, while a 100 {mu}m spacing irradiation tripled this median (67 days) but damaged normal tissue. the impact of the device dividing synchrotron beam into micro-beams, named multi sit collimator, was also demonstrated. combination of drugs with M.R.T. irradiation was tested. promising results (median survival time: 40 days and 30% of long term survivors) were obtained with an intratumoral injection of gadolinium coupled with a crossing M.R.T. irradiation at 460 Gy. Moreover, earlier M.R.T. irradiation (tumor at D10) quadrupled the median survival time (79 days) with 30% of long term survivors. A new imaging device to target the tumor before irradiation and an adapted collimator will increase the M.R.T. results. As the differences existing between tumoral models used in M.R.T. (9L models) and in S.S.R.T. (F98 models) are major, M.R.T./S.S.R.T. comparative experiments were realised on these two models. Results showed that the two techniques have the same efficacy on F98 model and that the M.R.T. is more effective on 9L model. This can help to define adapted tumor type for these techniques. (author)

  9. Angiographic Embolization of a Postpartum Vulvovaginal Hematoma in a Patient with Situs Inversus Totalis: An Effective Second-Line Treatment

    Directory of Open Access Journals (Sweden)

    Elias M. Dahdouh

    2013-01-01

    Full Text Available Situs inversus totalis is a rare congenital anomaly where asymmetrical positioning of internal organs may affect the surgical and radiological management of certain conditions. Vulvovaginal hematoma is a life-threatening complication of vaginal delivery whose primary treatment usually consists of incision and drainage of the hematoma and ligation of the responsible vessels, followed by wound packing. Failure of these measures to control the bleeding was previously considered as an indication for laparotomy to perform bilateral hypogastric artery ligation and, if needed, a hysterectomy. Relative to major abdominal surgery, selective percutaneous angiographic embolization offers considerable advantages and significant less morbidity. Indeed, angiographic embolization is routinely used as a measure to control refractory pelvic bleeding, though the literature and experience in women with situs inversus totalis are scarce. In this paper, we report a case of postpartum vulvovaginal hematoma in a patient with situs inversus, refractory to conventional treatment, where arteriographic embolization was successfully used to control the bleeding. The management of this obstetrical complication and the use of this minimally invasive technique are also reviewed. To the best of our knowledge, this is the first report in the literature describing the feasibility of this technique in a patient with situs inversus totalis.

  10. Investigation of time dependent stress at crown of second lining concrete of NATM tunnels for mitigating longitudinal cracks

    OpenAIRE

    Rankoth, Chamila Kumara

    2016-01-01

    In recent past, tunnel constructions in Japan have increased mainly due to the construction of revival road network in Tohoku region in northern part of Honshu Island. Many of the mountainous tunnels constructed in this area utilize New Austrian Tunneling method which has a superior versatility and low initial cost compared to many of other methods. These tunnels are comprised of a double shell lining system. The Inner lining is constructed with shotcrete and the outer lining, which is visibl...

  11. Cost-Effectiveness of Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia

    NARCIS (Netherlands)

    Mihajlovic, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomic, Zdenko; Postma, Maarten J.

    2013-01-01

    Background: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had

  12. The Prestige oil spill response in the French coastal waters : setting up a second-line response system

    International Nuclear Information System (INIS)

    Kerambrun, L.; Lavenant, M.; Cariou, G.; Poisson, H.; Goasguen, H.; Peltier, M.

    2005-01-01

    A heavy fuel oil spill from the Prestige oil tanker in early 2003 threatened the coastline of France, particularly the sensitive sandy dunes of the Aquitaine coast. The spill posed a long-term threat to two affected tourist islands that host a rich marine life, including the Marennes-Oleron oysters and juvenile eel fisheries. An oil spill response system was established by the French Maritime Affairs Department. The two-tiered response system was constructed with dynamic and static components and was adapted for strong tidal currents and muddy waters where fuel patches from the spill might not be visible. Local fishermen with knowledge of the waters used their trawlers and eel-fishing boats that were equipped with oil recovery trawls. A local netting device was also tested. The second response line for shallow waters consisted of small boats with net bags. The storage, transfer and treatment of the oily waste were controlled and available oil waste treatment procedures were assessed at local, regional and national levels for each type of oil waste fuel. 2 refs

  13. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  14. Massage therapy research review.

    Science.gov (United States)

    Field, Tiffany

    2016-08-01

    In this review, massage therapy has been shown to have beneficial effects on varying conditions including prenatal depression, preterm infants, full-term infants, autism, skin conditions, pain syndromes including arthritis and fibromyalgia, hypertension, autoimmune conditions including asthma and multiple sclerosis, immune conditions including HIV and breast cancer and aging problems including Parkinson's and dementia. Although many of the studies have involved comparisons between massage therapy and standard treatment control groups, several have compared different forms of massage (e.g. Swedish versus Thai massage), and different active therapies such as massage versus exercise. Typically, the massage therapy groups have experienced more positive effects than the control or comparison groups. This may relate to the massage therapy providing more stimulation of pressure receptors, in turn enhancing vagal activity and reducing cortisol levels. Some of the researchers have assessed physical, physiological and biochemical effects, although most have relied exclusively on self-report measures. Despite these methodological problems and the dearth of research from the U.S., the massage therapy profession has grown significantly and massage therapy is increasingly practiced in traditional medical settings, highlighting the need for more rigorous research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    International Nuclear Information System (INIS)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar; Sahoo, Ranjit Kumar; Seth, Amlesh

    2017-01-01

    The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, 177 Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic 68 Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly 177 Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity. 177 Lu

  16. Medical Therapy of Acromegaly

    Directory of Open Access Journals (Sweden)

    U. Plöckinger

    2012-01-01

    Full Text Available This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs, dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

  17. Collaboration in experiential therapy.

    Science.gov (United States)

    Berdondini, Lucia; Elliott, Robert; Shearer, Joan

    2012-02-01

    We offer a view of the nature and role of client-therapist collaboration in experiential psychotherapy, focusing on Gestalt and emotion-focused therapy (EFT). We distinguish between the necessary condition of mutual trust (the emotional bond between client and therapist) and effective collaboration (regarding the goals and tasks of therapy). Using a case study of experiential therapy for social anxiety, we illustrate how the development of collaboration can be both complex and pivotal for therapeutic success, and how it can involve client and therapist encountering one another through taking risks by openly and nonjudgementally disclosing difficult experiences in order to enrich and advance the work. © 2012 Wiley Periodicals, Inc.

  18. Feminist music therapy pedagogy

    DEFF Research Database (Denmark)

    Hahna, Nicole; Swantes, Melody

    2011-01-01

    This study surveyed 188 music therapy educators regarding their views and use of feminist pedagogy and feminist music therapy. The purpose of this study was two-fold: (a) to determine how many music therapy educators used feminist pedagogy and (b) to determine if there was a relationship between......) participatory learning, (b) validation of personal experience/development of confidence, (c) political/social activism, and (d) critical thinking/ open-mindedness. The results revealed that 46% (n = 32) of participants identified as feminist music therapists and 67% (n = 46) of participants identified as using...

  19. Complications of cancer therapy

    International Nuclear Information System (INIS)

    Moskowitz, P.S.; Parker, B.R.

    1985-01-01

    The purpose of this chapter is to review systematically the toxicity of contemporary chemotherapy and irradiation on normal tissues of growing children. Whenever possible, the separate toxicity of chemotherapy, irradiation, and combination therapy is addressed. However, it is not always possible to quantitate specifically such reactions in the face of multiple drug therapy, which may enhance radiation injury or reactivate prior radiation injury. Prior detailed reviews have provided important sources of information concerning radiation injury for this more general discussion. The information provided will assist both the clinician and the radiologist in the recognition of early and late complications of therapy in pediatric oncology

  20. Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations.

    Science.gov (United States)

    Valli, Piero V; Mertens, Joachim C; Kröger, Arne; Gubler, Christoph; Gutschow, Christian; Schneider, Paul M; Bauerfeind, Peter

    2018-02-01

     Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS).  Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique.  Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred. CONCLUSION : SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results. © Georg Thieme Verlag KG Stuttgart · New York.