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

    DEFF Research Database (Denmark)

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

    2004-01-01

    The increasing prevalence of drug-resistant tuberculosis necessitates rapid and accurate susceptibility testing. The nonradiometric BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT) system for susceptibility testing was evaluated on 222 clinical Mycobacterium tuberculosis complex isolates...... MGIT system is a rapid and reliable alternative for susceptibility testing of M. tuberculosis complex to first-line drugs....

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  3. Levofloxacin-Based First-Line Therapy versus Standard First-Line Therapy for Helicobacter pylori Eradication: Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Peedikayil, Musthafa Chalikandy; AlSohaibani, Fahad Ibrahim; Alkhenizan, Abdullah Hamad

    2014-01-01

    Background First-line levofloxacin-based treatments eradicate Helicobacter pylori with varying success. We examined the efficacy and safety of first-line levofloxacin-based treatment in comparison to standard first-line therapy for H pylori eradication. Materials and Methods We searched literature databases from Medline, EMBASE, and the Cochrane Register of Randomized Controlled Trials through March 2013 for randomized controlled trials comparing first-line levofloxacin and standard therapy. We included randomized controlled trials conducted only on naïve H pylori infected patients in adults. A systematic review was conducted. Meta-analysis was performed with Review Manager 5.2. Treatment effect was determined by relative risk with a random or fixed model by the Mantel-Haenszel method. Results Seven trials were identified with 888 patients receiving 7 days of first-line levofloxacin and 894 treated with standard therapy (Amoxicillin, Clarithromycin and proton pump inhibitor) for 7 days. The overall crude eradication rate in the Levofloxacin group was 79.05% versus 81.4% in the standard group (risk ratio 0.97; 95% CI; 0.93, 1.02). The overall dropout was 46 (5.2%) in the levofloxacin group and 52 (5.8%) for standard therapy. The dizziness was more common among group who took Levofloxacin based treatment and taste disturbance was more common among group who took standard therapy. Meta-analysis of overall adverse events were similar between the two groups with a relative risk of 1.06 (95% CI 0.72, 1.57). Conclusion Helicobacter pylori eradication with 7 days of Levofloxacin-based first line therapy was safe and equal compared to 7 days of standard first-line therapy. PMID:24465624

  4. Three drugs vs two drugs first-line chemotherapy regimen in advanced gastric cancer patients: a retrospective analysis.

    Science.gov (United States)

    Bittoni, Alessandro; Del Prete, Michela; Scartozzi, Mario; Pistelli, Mirco; Giampieri, Riccardo; Faloppi, Luca; Bianconi, Maristella; Cascinu, Stefano

    2015-01-01

    The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients in the clinical practice. Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A = three drugs; group B = two drugs). A total of 425 patients were eligible for our analysis. 216 patients (50.8 %) received three chemotherapeutic agents (group A) and 209 patients (49.2 %) received a two drugs regimen as first-line combination chemotherapy (group B). RR for group A and B was 44 and 29.6 %, respectively (p = 0.0005), median PFS was 7.3 months in group A and 4.5 months in group B (p = 0.0007). No significant difference was found in terms of OS. The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, the use of a sequential approach may represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS.

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

    African Journals Online (AJOL)

    status on the risk of developing adverse events to first line anti-TB therapy. Method: The study was ... used in evaluating adverse drugs events and reactions. 8. In addition ..... drugs on directly observed (DOTs) therapy. Their study showed an ...

  6. Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia

    NARCIS (Netherlands)

    Fibriani, A.; Wisaksana, R.; Indrati, A.; Hartantri, Y.; Vijver, D. van de; Schutten, M.; Alisjahbana, B.; Sudjana, P.; Boucher, C.A.B.; Crevel, R. van; Ven, A. van der

    2013-01-01

    The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of

  7. First-line anti-tubercular drug resistance of Mycobacterium tuberculosis in IRAN: a systematic review

    Directory of Open Access Journals (Sweden)

    Babak Pourakbari

    2016-07-01

    Full Text Available Background: The spread of drug-resistant tuberculosis (TB is one of the major public health problems in the world. Surveillance of anti-TB drug resistance is important for monitoring of TB control strategies. The occurrence of drug resistance, particularly multi-drug resistance Mycobacterium tuberculosis (MDR, defined as resistance to at least rifampicin (RIF and isoniazid (INH, has become a significant public health dilemma. However, the status of drug-resistance TB in Iran has been reported inconsistently. Therefore, the aim of this study was to summarize reports on first-line anti-tubercular drug resistance of M. tuberculosis in Iran.Material and Methods: We systematically reviewed published studies on drug-resistant M. tuberculosis in Iran. Search terms ̎Mycobacterium tuberculosis susceptibility ̎ and ̎Mycobacterium tuberculosis resistant ̎ were used in PubMed, Google Scholar, Magiran, IrMedex and SID. Results: Fifty- two eligible articles, published during 1998-2014, were included in this review. Most studies were conducted in Tehran. The most common laboratory method was used for anti-drug resistant of M. tuberculosis was Agar proportion. The average prevalence of resistant against INH in Tehran was 26%, RIF 23%, streptomycin (SM 22.5% and ethambotol (EMB 16% by Agar proportion method. In general, resistance to INH was more common than RIF, SM and EMB in Tehran. The average prevalence of resistant against INH in Tabriz was 15%, RIF 5%, SM 19% and EMB 2% by proportion. The highest resistance to first-line drugs was seen in Tehran.Conclusions: In conclusion, this systematic review summarized the prevalence and distribution of first-line anti-tubercular drug resistance of M. tuberculosis in Iran. Our results suggested that effective strategies to minimize the acquired drug resistance, to control the transmission of resistance and improve the diagnosis measures for TB control in Iran.

  8. First-Line Anti-Tubercular Drug Resistance of Mycobacterium tuberculosis in IRAN: A Systematic Review.

    Science.gov (United States)

    Pourakbari, Babak; Mamishi, Setareh; Mohammadzadeh, Mona; Mahmoudi, Shima

    2016-01-01

    The spread of drug-resistant tuberculosis (TB) is one of the major public health problems through the world. Surveillance of anti-TB drug resistance is essential for monitoring of TB control strategies. The occurrence of drug resistance, particularly multi-drug resistance Mycobacterium tuberculosis (MDR), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), has become a significant public health dilemma. The status of drug-resistance TB in Iran, one of the eastern Mediterranean countries locating between Azerbaijan and Armenia and high-TB burden countries (such as Afghanistan and Pakistan) has been reported inconsistently. Therefore, the aim of this study was to summarize reports of first-line anti-tubercular drug resistance in M. tuberculosis in Iran. We systematically reviewed published studies on drug-resistant M. tuberculosis in Iran. The search terms were "Mycobacterium tuberculosis susceptibility" or "Mycobacterium tuberculosis resistant" and Iran. Fifty-two eligible articles, published during 1998-2014, were included in this review. Most of the studies were conducted in Tehran. The most common used laboratory method for detecting M. tuberculosis drug resistant was Agar proportion. The highest resistance to first-line drugs was seen in Tehran, the capital city of Iran. The average prevalence of isoniazid (INH), rifampin (RIF), streptomycin (SM), and ethambotol (EMB) resistance via Agar proportion method in Tehran was 26, 23, 22.5, and 16%, respectively. In general, resistance to INH was more common than RIF, SM, and EMB in Tehran Conclusions: In conclusion, this systematic review summarized the prevalence and distribution of first-line anti-tubercular drug resistance of M. tuberculosis in Iran. Our results suggested that effective strategies to minimize the acquired drug resistance, to control the transmission of resistance and improve the diagnosis measures for TB control in Iran.

  9. Effectiveness and Safety of Concurrent Use of First-Line Antiretroviral and Antituberculous Drugs in Rwanda

    Directory of Open Access Journals (Sweden)

    Justin Ntokamunda Kadima

    2014-01-01

    Full Text Available Background. Overlapping toxicity between drugs used for HIV and TB could complicate the management of HIV/TB coinfected patients, particularly those carrying multiple opportunistic infections. This study aimed to evaluate the clinical outcomes and adverse drug events in HIV patients managed with first-line antiretroviral and first-line anti-TB drugs. Methods. This is a retrospective study utilizing medical dossiers from single-HIV infected and HIV/TB coinfected patients already initiated on ART. Predictors of outcomes included changes in CD4 cells/mm3, body weight, physical improvement, death rate, and adverse drug reactions. Results. Records from 60 HIV patients and 60 HIV/TB patients aged between 20 and 58 years showed that all clinical indicators of effectiveness were better in single-HIV infected than in HIV/TB coinfected patients: higher CD4 cell counts, better physical improvement, and low prevalence of adverse drug events. The most frequently prescribed regimen was TDF/3TC/EFV+RHZE. The mortality rate was 20% in HIV/TB patients compared to 8.3% in the single-HIV group. Conclusion. Treatment regimens applied are efficient in controlling the progression of the infection. However, attention should be paid to adjust dosing when combining nonnucleoside antiretrovirals (EFV and NVR with anti-TB drugs to minimize the risk of death by drug intoxication.

  10. Is Resistance to Dolutegravir Possible When This Drug Is Used in First-Line Therapy?

    Directory of Open Access Journals (Sweden)

    Thibault Mesplède

    2014-08-01

    Full Text Available Dolutegravir (DTG is an HIV integrase inhibitor that was recently approved for therapy by the Food and Drug Administration in the United States. When used as part of first-line therapy, DTG is the only HIV drug that has not selected for resistance mutations in the clinic. We believe that this is due to the long binding time of DTG to the integrase enzyme as well as greatly diminished replication capacity on the part of viruses that might become resistant to DTG. We further speculate that DTG might be able to be used in strategies aimed at HIV eradication.

  11. Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic review and meta-analysis.

    Science.gov (United States)

    Gegia, Medea; Winters, Nicholas; Benedetti, Andrea; van Soolingen, Dick; Menzies, Dick

    2017-02-01

    The results of some reports have suggested that treatment of isoniazid-resistant tuberculosis with the recommended regimens of first-line drugs might be suboptimal. We updated a previous systematic review of treatment outcomes associated with use of first-line drugs in patients with tuberculosis resistant to isoniazid but not rifampicin. In this systematic review, we updated the results of a previous review to include randomised trials and cohort studies published in English, French, or Spanish to March 31, 2015, containing results of standardised treatment of patients with bacteriologically confirmed isoniazid-resistant tuberculosis (but not multidrug-resistant tuberculosis-ie, not resistant to rifampicin) in whom failure and relapse were bacteriologically confirmed. Results in patients with drug-sensitive tuberculosis included in the same studies were also analysed. We pooled treatment outcomes with random-effects meta-analysis. We identified 19 cohort studies and 33 trials with 3744 patients with isoniazid-resistant tuberculosis and 19 012 patients with drug-sensitive disease. The pooled rates of failure or relapse, or both, and acquired drug resistance with all drug regimens were 15% (95% CI 12-18) and 3·6% (2-5), respectively, in patients with isoniazid-resistant tuberculosis and 4% (3-5) and 0·6% (0·3-0·9) in those with drug-sensitive tuberculosis. Of patients with initial isoniazid-resistant tuberculosis with acquired drug resistance, 96% (93-99) had acquired multidrug-resistant disease. Treatment of isoniazid-resistant tuberculosis with the WHO standard regimen for new patients resulted in treatment failure, relapse, and acquired multidrug resistance in 11% (6-17), 10% (5-15) and 8% (3-13), respectively; treatment with the standard WHO regimen for previously treated patients resulted in treatment failure in 6% (2-10), relapse in 5% (2-8), and acquisition of multidrug resistance in 3% (0-6). For patients with drug-sensitive disease treated with the

  12. Resistance to first-line antituberculosis drugs in Spain, 2010-2011. RETUBES Study.

    Science.gov (United States)

    Blanquer, Rafael; Rodrigo, Teresa; Casals, Martí; Ruiz Manzano, Juan; García-García, José María; Calpe, José Luís; Valencia, Eulalia; Pascual, Teresa; Mir, Isabel; Jiménez, María Ángeles; Cañas, Fernando; Vidal, Rafael; Penas, Antón; Caylà, Joan A

    2015-01-01

    The magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. Prospective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. A total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR=2.3; 95%CI: .98-5.67 and OR=2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03). The rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance. Copyright © 2014. Published by Elsevier Espana.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6...... for baseline characteristics and clinical status at 2, 4 and 6 months after the initiation of treatment. At a 1 year follow-up, therapy failure was defined as death or a relapse of tuberculosis. RESULTS: Plasma concentrations below the normal ranges were frequently observed: isoniazid in 71%, rifampicin in 58......%, ethambutol in 46%, pyrazinamide in 10% and both isoniazid and rifampicin in 45% of the patients. The plasma concentrations of isoniazid correlated inversely with the C-reactive protein level at the time of sampling (P = 0.001). During 1 year of follow-up, therapy failure occurred in five patients. Therapy...

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

    Science.gov (United States)

    Franco, Antonia Mr; Grafova, Iryna; Soares, Fabiane V; Gentile, Gennaro; Wyrepkowski, Claudia Dc; Bolson, Marcos A; Sargentini, Ézio; Carfagna, Cosimo; Leskelä, Markku; Grafov, Andriy

    Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V) complexes are commercialized as sodium stibogluconate (Pentostam(®)) and meglumine antimoniate (MA) (Glucantime(®)). Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb(5+) toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V) concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5·nH2O nanoparticles (NPs), instead of molecular drugs. Sb2O5·nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5·nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V) NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35-45 nm. In vitro tests demonstrated a 2.5-3 times higher antiparasitic activity of Sb (V) nanohybrid hydrosols, when compared to MA solution. A similar comparison for in vivo treatment of experimental cutaneous leishmaniasis with Sb(5+) nanohybrids showed a 1.75-1.85 times more effective decrease in the lesions. Microimages of tissue fragments confirmed the presence of NPs inside the cytoplasm of infected macrophages. Sb2O5·nH2O hydrosols are proposed as a new form of treatment for cutaneous leishmaniasis caused by Leishmania amazonensis. The NPs penetrate directly into the affected cells, creating a high local concentration of the drug, a precondition to overcoming the parasite resistance to molecular forms of pentavalent antimonials. The nanohybrids are more effective at a lower dose, when compared to MA, the molecular drug. Our data suggest that the new form of treatment has the potential to

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

    Science.gov (United States)

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

    2016-06-28

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

  16. Underreporting of side effects of standard first-line ART in the routine setting in Blantyre, Malawi.

    Science.gov (United States)

    Tapsfield, Julia; Mathews, Teena; Lungu, Molly; van Oosterhout, Joep J

    2011-12-01

    In the Malawi ART programme, 92% of 250,000 patients are using the standard first-line regime of stavudine-lamivudine-nevaripine. National ART reports indicate side effects, much less than expected from literature. We interviewed adult patients on standard first-line ART for at least one year, after routine visits to an urban clinic in Blantyre, Malawi. We determined the prevalence of symptoms that are common side-effects, described discrepancies between symptoms that patients reported to us and those that had been recorded by attending staff as side-effects in the point-of-care electronic monitoring system, and studied factors associated with such discrepancies. Of 170 participants, 75 (44%) reported at least one symptom, most common were symptoms suggesting peripheral neuropathy (n=57) and lipodystrophy (n=16). Forty-six (66%) symptomatic patients said they reported symptoms to attending ART staff. Side-effects were recorded in the clinic database for just 4 patients. Toxicity recording was too low for meaningful analysis of factors associated with discrepancies between reporting and recording of side-effects. The prevalence of symptoms indicating characteristic side-effects of the standard first-line regimen was 39% based on interviews, and 2% in the electronic monitoring system. There was gross under-recording of side-effects in this setting, mainly due to not recording by ART staff. Pressure of work and insufficient perceived benefit of side-effect recording are suspected causes. Local and national ART reports do not reflect the true toxicity of the standard first line regimen.

  17. First-Line Anti-Tubercular Drug Resistance of Mycobacterium tuberculosis in IRAN: A Systematic Review

    OpenAIRE

    Babak Pourakbari; Setareh Mamishi; Mona Mohammadzadeh; Shima Mahmoudi

    2016-01-01

    Background: The spread of drug-resistant tuberculosis (TB) is one of the major public health problems through the world. Surveillance of anti-TB drug resistance is essential for monitoring of TB control strategies. The occurrence of drug resistance, particularly multi-drug resistance Mycobacterium tuberculosis (MDR), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), has become a significant public health dilemma. The status of drug-resistance TB in Iran, one of the easte...

  18. First-line antituberculosis drugs disrupt endocrine balance and induce ovarian and uterine oxidative stress in rats.

    Science.gov (United States)

    Adebayo, Olayinka A; Adesanoye, Omolola A; Abolaji, Olalekan A; Kehinde, Aderemi O; Adaramoye, Oluwatosin A

    2017-11-08

    The first-line antituberculosis (anti-TB) drugs, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA), are effective in the treatment of pulmonary tuberculosis. However, the toxicity of these drugs in the clinical setting limits their use. Here, we evaluated the effects of anti-TB drugs on the reproductive system in female rats. Thirty-five female Wistar rats were assigned into five groups of seven animals each. The control group received normal saline, whereas others received INH (5 mg/kg), RIF (10 mg/kg), EMB (15 mg/kg), and PZA (15 mg/kg) through gavage thrice a week for 8 consecutive weeks. Administration of anti-TB drugs significantly (pline anti-TB drugs elicited reproductive toxicity in the uterus and ovaries of rats through mechanisms that involved oxidative stress.

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

    African Journals Online (AJOL)

    seropositive patients: report on six cases. East Afr Med J 1991;68(1):64-66. 25. Gulbay BE, Gurkan OU, Yildiz OA, et al. Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis.

  20. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Comparing the effects of first-line antiepileptic drugs on the gait of dogs with idiopathic epilepsy.

    Science.gov (United States)

    Suiter, E J; Packer, R M A; Volk, H A

    2016-06-25

    Idiopathic epilepsy (IE) is a common chronic neurological disease of the dog. Previous studies of anti-epileptic drug (AED) treatment have indicated that acceptable AED adverse effects are as important to owners as reductions in seizure frequency. AEDs in both dogs and human beings are frequently associated with the adverse-effect ataxia. The aim of this study was to compare ataxia levels in dogs with IE treated chronically with phenobarbitone or imepitoin, the two currently available first-line AED treatments. The gait of 6 imepitoin-treated dogs, 8 phenobarbitone-treated dogs and 10 age-matched healthy control dogs were compared. Fifty strides from a walking gait were analysed for each dog, quantifying ataxia via the variability in six established gait parameters. Three variables differed significantly between groups: lateral distance between (i) pelvic paw placements, (ii) thoracic paw placements and (iii) stance time, which were significantly more variable in the phenobarbitone-treated dogs than imepitoin-treated or control dogs. These results indicate that dogs treated with phenobarbitone experience ataxia compared with controls and imepitoin-treated dogs. Conversely, there was no difference between imepitoin-treated dogs and controls. These results along with further research are needed to quantify AEDs adverse effects, to help vets and owners make more informed drug-choices. British Veterinary Association.

  3. Detection of First-Line Drug Resistance Mutations and Drug-Protein Interaction Dynamics from Tuberculosis Patients in South India.

    Science.gov (United States)

    Nachappa, Somanna Ajjamada; Neelambike, Sumana M; Amruthavalli, Chokkanna; Ramachandra, Nallur B

    2017-08-16

    Diagnosis of drug-resistant tuberculosis predominantly relies on culture-based drug susceptibility testing, which take weeks to produce a result and a more time-efficient alternative method is multiplex allele-specific PCR (MAS-PCR). Also, understanding the role of mutations in causing resistance helps better drug designing. To evaluate the ability of MAS-PCR in the detection of drug resistance and to understand the mechanism of interaction of drugs with mutant proteins in Mycobacterium tuberculosis. Detection of drug-resistant mutations using MAS-PCR and validation through DNA sequencing. MAS-PCR targeted five loci on three genes, katG 315 and inhA -15 for the drug isoniazid (INH), and rpoB 516, 526, and 531 for rifampicin (RIF). Furthermore, the sequence data were analyzed to study the effect on interaction of the anti-TB drug molecule with the target protein using in silico docking. We identified drug-resistant mutations in 8 out of 114 isolates with 2 of them as multidrug-resistant TB using MAS-PCR. DNA sequencing confirmed only six of these, recording a sensitivity of 85.7% and specificity of 99.3% for MAS-PCR. Molecular docking showed estimated free energy of binding (ΔG) being higher for RIF binding with RpoB S531L mutant. Codon 315 in KatG does not directly interact with INH but blocks the drug access to active site. We propose DNA sequencing-based drug resistance detection for TB, which is more accurate than MAS-PCR. Understanding the action of resistant mutations in disrupting the normal drug-protein interaction aids in designing effective drug alternatives.

  4. 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

  5. Pattern of drug resistance of Mycobacterium tuberculosis clinical isolates to first-line antituberculosis drugs in pulmonary cases

    Science.gov (United States)

    Kalo, Deepika; Kant, Surya; Srivastava, Kanchan; Sharma, Ajay K.

    2015-01-01

    Context: Mycobacterium tuberculosis (MTB), the human pathogen causes Tuberculosis (TB). It is a highly infectious and globally pandemic disease. The severity increases when the MTB becomes resistant to antituberculosis drugs. India is reported to be in the second place, with the highest number of drug-resistant TB cases. The treatment of drug-resistant TB is even more complicated. Materials and Methods: The present study comprises of 159 TB patients, in which 88 are reported to have drug-resistant TB (55.3%). All the patients are in the age group of 18–70 years. Patients having extrapulmonary TB and diabetes were excluded from the study. The collected samples were processed and stained for acid fastness and smear positivity. They were subjected to inoculation on Lowenstein–Jensen (LJ) slants. Results: The results showed that out of the four drugs — Streptomycin, Isoniazid, Rifampicin, and Ethambutol — the resistant cases reported in Streptomycin were 45 (24.9%), whereas, in Isoniazid, Rifampicin, and Ethambutol, the resistant cases were 62 (34.2%), 27 (14.9%), and 47 (26.0%), respectively. Isoniazid showed the highest percentage of resistance among the patients. Conclusion: Effective measures such as convincing the patients to take the prescribed drugs and follow the five major strategies under the Directly Observed Treatment, Short Course (DOTS), could help in managing such cases. PMID:26180382

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

    Science.gov (United States)

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

    2017-01-03

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

  7. Transmission of multi-drug resistant tuberculosis in Mongolia is driven by Beijing strains of Mycobacterium tuberculosis resistant to all first-line drugs.

    Science.gov (United States)

    Gurjav, Ulziijargal; Erkhembayar, Baasansuren; Burneebaatar, Buyankhishig; Narmandakh, Erdenegerel; Tumenbayar, Oyuntuya; Hill-Cawthorne, Grant A; Marais, Ben J; Sintchenko, Vitali

    2016-12-01

    Mongolia has high and rising rates of multi-drug resistant tuberculosis (MDR-TB). Spatio-temporal and programmatic evidence suggests a major contribution from MDR-TB transmission, but genotypic evidence has not been assessed. All MDR-TB cases identified during 2012 were examined. Demographic and bacteriological data were obtained from the National Tuberculosis Reference Laboratory. Isolates of Mycobacterium tuberculosis from culture-confirmed category 1 treatment failures were genotyped using 24-loci mycobacterium interspersed repetitive unit (MIRU-24) analysis. Of the 210 MDR-TB cases identified, 115 (54.8%) were treatment failures (34.8% category 1; 20.0% category 2). Streptomycin resistance was present in 156 (74.3%) cases; including 55/73 (75.3%) category 1 treatment failures who had never been exposed to streptomycin. Among category 1 treatment failures, Beijing lineage strains predominated (88.0%; 59/67 of genotyped isolates). MIRU-24 clustering was documented in 62.7% (42/67) of strains; 55.2% (37/67) remained clustered when drug susceptibility test results were considered. In total 59.5% (25/42) of clustered strains were Beijing lineage and demonstrated in-vitro resistance to all first-line drugs tested. The MDR-TB epidemic in Mongolia appears to be driven by primary transmission of Beijing lineage strains resistant to all first-line drugs. Enhanced infection control strategies together with early MDR-TB case detection and appropriate treatment are necessary to limit escalation of the MDR-TB epidemic. Copyright © 2016. Published by Elsevier Ltd.

  8. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12)

    DEFF Research Database (Denmark)

    du Bois, Andreas; Kristensen, Gunnar; Ray-Coquard, Isabelle

    2016-01-01

    ; and one due to peritonitis) and in one patient in the placebo group (cause unknown). INTERPRETATION: Nintedanib in combination with carboplatin and paclitaxel is an active first-line treatment that significantly increases progression-free survival for women with advanced ovarian cancer, but is associated......BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated......) and paclitaxel (175 mg/m(2)) in addition to either 200 mg of nintedanib (nintedanib group) or placebo (placebo group) twice daily on days 2-21 of every 3-week cycle for up to 120 weeks. Patients, investigators, and independent radiological reviewers were masked to treatment allocation. The primary endpoint...

  9. HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa.

    Science.gov (United States)

    Kityo, Cissy; Thompson, Jennifer; Nankya, Immaculate; Hoppe, Anne; Ndashimye, Emmanuel; Warambwa, Colin; Mambule, Ivan; van Oosterhout, Joep J; Wools-Kaloustian, Kara; Bertagnolio, Silvia; Easterbrook, Philippa J; Mugyenyi, Peter; Walker, A Sarah; Paton, Nicholas I

    2017-06-01

    To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed. Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate-/high-level resistance and factors including REGA subtype, first-line antiretroviral therapy drugs, CD4, and VL at failure. The median first-line treatment duration was 4 years (interquartile range 30-43 months); 42% of participants had VL ≥100,000 copies/mL and 63% participants had CD4 reverse transcriptase inhibitor mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, and H221Y). The presence of tenofovir resistance was similar between subtypes [P (adjusted) = 0.32], but resistance to zidovudine, abacavir, etravirine, or rilpivirine was more common in subtype-C than in subtype-D/subtype-A [P (adjusted) reverse transcriptase inhibitor and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens.

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

    Science.gov (United States)

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

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) 2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy. PMID:25141905

  11. Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug

    Directory of Open Access Journals (Sweden)

    Gonzalez-Block Miguel A

    2005-10-01

    Full Text Available Abstract Introduction Research is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research evidence into drug policy action in Tanzania is often constrained by poor communication between researchers and policy decision-makers, individual perceptions or attitudes towards the drug and hesitation by some policy decision-makers to approve change when they anticipate possible undesirable repercussions should the policy change as proposed. Internationally, literature on the role of researchers on national antimalarial drug policy change is limited. Objectives To describe the (a role of researchers in producing evidence that influenced the Tanzanian government replace chloroquine (CQ with sulfadoxine-pyrimethamine (SP as the first-line drug and the challenges faced in convincing policy-makers, general practitioners, pharmaceutical industry and the general public on the need for change (b challenges ahead before a new drug combination treatment policy is introduced in Tanzania. Methods In-depth interviews were held with national-level policy-makers, malaria control programme managers, pharmaceutical officers, general medical practitioners, medical research library and publications officers, university academicians, heads of medical research institutions and district and regional medical officers. Additional data were obtained through a review of malaria drug policy documents and participant observations were also done. Results In year 2001, the Tanzanian Government officially changed its malaria treatment policy guidelines whereby CQ – the first-line drug for a long time was replaced with SP. This policy decision was supported by research evidence indicating parasite resistance to CQ and clinical CQ treatment failure rates to have reached intolerable levels as compared to SP and amodiaquine (AQ. Research also indicated that since SP was also facing

  12. High Levels of Dual-Class Drug Resistance in HIV-Infected Children Failing First-Line Antiretroviral Therapy in Southern Ethiopia.

    Science.gov (United States)

    Tadesse, Birkneh Tilahun; Kinloch, Natalie N; Baraki, Bemuluyigza; Lapointe, Hope R; Cobarrubias, Kyle D; Brockman, Mark A; Brumme, Chanson J; Foster, Byron A; Jerene, Degu; Makonnen, Eyasu; Aklillu, Eleni; Brumme, Zabrina L

    2018-02-01

    Clinical monitoring of pediatric HIV treatment remains a major challenge in settings where drug resistance genotyping is not routinely available. As a result, our understanding of drug resistance, and its impact on subsequent therapeutic regimens available in these settings, remains limited. We investigate the prevalence and correlates of HIV-1 drug resistance among 94 participants of the Ethiopia Pediatric HIV Cohort failing first-line combination antiretroviral therapy (cART) using dried blood spot-based genotyping. Overall, 81% (73/90) of successfully genotyped participants harbored resistance mutations, including 69% (62/90) who harbored resistance to both Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs). Strikingly, 42% of resistant participants harbored resistance to all four NRTIs recommended for second-line use in this setting, meaning that there are effectively no remaining cART options for these children. Longer cART duration and prior regimen changes were significantly associated with detection of drug resistance mutations. Replicate genotyping increased the breadth of drug resistance detected in 34% of cases, and thus is recommended for consideration when typing from blood spots. Implementation of timely drug resistance testing and access to newer antiretrovirals and drug classes are urgently needed to guide clinical decision-making and improve outcomes for HIV-infected children on first-line cART in Ethiopia.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  14. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

    DEFF Research Database (Denmark)

    Hofstra, L Marije; Sauvageot, Nicolas; Albert, Jan

    2016-01-01

    BACKGROUND:  Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management......, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS:  Demographic, clinical, and virological data from 4140 antiretroviral-naive human...... immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002...

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

    Science.gov (United States)

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

    2012-10-01

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

  16. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  17. The preparation of core/shell structured microsphere of multi first-line anti-tuberculosis drugs and evaluation of biological safety.

    Science.gov (United States)

    Zeng, Hao; Pang, Xiaoyang; Wang, Shuo; Xu, Zhengquan; Peng, Wei; Zhang, Penghui; Zhang, Yupeng; Liu, Zheng; Luo, Chengke; Wang, Xiyang; Nie, Hemin

    2015-01-01

    To introduce a modified method, namely coaxial electrohydrodynamic atomization for the fabrication of distinct core/shell structured microspheres of four first-line ant-tuberculosis drugs with different characteristics in hydrophilic properties in one single step. In group B, we prepared microspheres in which the core and the shell contain hydrophobic and hydrophilic drugs, respectively. In contrast, in group C, the opposite is prepared. The detection of encapsulation efficiency and in vitro release test were performed to confirm the feasibility of the drug-loaded core/shell structured microspheres. Moreover, cell culture experiments and animal experiments have been carried out to evaluate the biological safety of different microspheres in cell growth, cell viability, osteogenesis and migration of BMSCs in vitro and the bone fusion in a bone deficits model in SD rat. Meanwhile, the distribution of drugs and liver and kidney toxicity were monitored. The release patterns of the two groups are significantly different. The release of drugs from Group B microspheres is rather sequential, whereas group C microspheres release drugs in a parallel (co-release) manner. And various concentrations of carrier materials produces core/shell structured microspheres with different appearance. Moreover, the biological safety of core/shell structured microspheres was testified to be satisfactory. These findings present the advantages and possible application of this kind of multi-drug release system in treating skeletal tuberculosis. Moreover, the characteristic sequential release of multi-drugs can be controlled and adjusted based on treatment need and used in treating other disorders.

  18. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial.

    Science.gov (United States)

    du Bois, Andreas; Kristensen, Gunnar; Ray-Coquard, Isabelle; Reuss, Alexander; Pignata, Sandro; Colombo, Nicoletta; Denison, Ursula; Vergote, Ignace; Del Campo, Jose M; Ottevanger, Petronella; Heubner, Martin; Minarik, Thomas; Sevin, Emmanuel; de Gregorio, Nikolaus; Bidziński, Mariusz; Pfisterer, Jacobus; Malander, Susanne; Hilpert, Felix; Mirza, Mansoor R; Scambia, Giovanni; Meier, Werner; Nicoletto, Maria O; Bjørge, Line; Lortholary, Alain; Sailer, Martin Oliver; Merger, Michael; Harter, Philipp

    2016-01-01

    : nintedanib group 191 [21%] of 902 grade 3 and three [nintedanib group 180 [20%] grade 3 and 200 (22%) grade 4 vs placebo group 90 [20%] grade 3 and 72 [16%] grade 4; thrombocytopenia: 105 [12%] and 55 [6%] vs 21 [5%] and eight [2%]; anaemia: 108 [12%] and 13 [1%] vs 26 [6%] and five [1%]). Serious adverse events were reported in 376 (42%) of 902 patients in the nintedanib group and 155 (34%) of 450 in the placebo group. 29 (3%) of 902 patients in the nintedanib group experienced serious adverse events associated with death compared with 16 (4%) of 450 in the placebo group, including 12 (1%) in the nintedanib group and six (1%) in the placebo group with a malignant neoplasm progression classified as an adverse event by the investigator. Drug-related adverse events leading to death occurred in three patients in the nintedanib group (one without diagnosis of cause; one due to non-drug-related sepsis associated with drug-related diarrhoea and renal failure; and one due to peritonitis) and in one patient in the placebo group (cause unknown). Nintedanib in combination with carboplatin and paclitaxel is an active first-line treatment that significantly increases progression-free survival for women with advanced ovarian cancer, but is associated with more gastrointestinal adverse events. Future studies should focus on improving patient selection and optimisation of tolerability. Boehringer Ingelheim. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Mycobacterium tuberculosis Genotypes Determined by Spoligotyping to Be Circulating in Colombia between 1999 and 2012 and Their Possible Associations with Transmission and Susceptibility to First-Line Drugs.

    Directory of Open Access Journals (Sweden)

    Gloria Puerto

    Full Text Available Tuberculosis (TB remains a primary public health problem worldwide. The number of multidrug-resistant tuberculosis (MDR TB cases has increased in recent years in Colombia. Knowledge of M. tuberculosis genotypes defined by spoligotyping can help determine the circulation of genotypes that must be controlled to prevent the spread of TB.To describe the genotypes of M. tuberculosis using spoligotyping in resistant and drug-sensitive isolates and their possible associations with susceptibility to first-line drugs.An analytical observational study was conducted that included 741 isolates of M. tuberculosis from patients. The isolates originated from 31 departments and were obtained by systematic surveillance between 1999 and 2012.In total 61.94% of the isolates were resistant to 1 or more drugs, and 147 isolates were MDR. In total, 170 genotypes were found in the population structure of Colombian M. tuberculosis isolates. The isolates were mainly represented by four families: LAM (39.9%, Haarlem (19%, Orphan (17% and T (9%. The SIT42 (LAM 9 was the most common genotype and contained 24.7% of the isolates, followed by the genotypes SIT62 (Haarlem1, SIT53 (T1, and SIT50 (H3. A high clustering of isolates was evident with 79.8% of the isolates classified into 32 groups. The Beijing family was associated with resistant isolates, whereas the Haarlem and T families were associated with sensitive isolates. The Haarlem family was also associated with grouped isolates (p = 0.031.A high proportion (approximately 80% of isolates was found in clusters; these clusters were not associated with resistance to first-line drugs. The Beijing family was associated with drug resistance, whereas the T and Haarlem families were associated with susceptibility in the Colombian isolates studied.

  20. Mycobacterium tuberculosis Genotypes Determined by Spoligotyping to Be Circulating in Colombia between 1999 and 2012 and Their Possible Associations with Transmission and Susceptibility to First-Line Drugs

    Science.gov (United States)

    Puerto, Gloria; Erazo, Lina; Wintaco, Maira; Castro, Claudia; Ribón, Wellman; Guerrero, Martha Inírida

    2015-01-01

    Introduction Tuberculosis (TB) remains a primary public health problem worldwide. The number of multidrug-resistant tuberculosis (MDR TB) cases has increased in recent years in Colombia. Knowledge of M. tuberculosis genotypes defined by spoligotyping can help determine the circulation of genotypes that must be controlled to prevent the spread of TB. Objective To describe the genotypes of M. tuberculosis using spoligotyping in resistant and drug-sensitive isolates and their possible associations with susceptibility to first-line drugs. Methods An analytical observational study was conducted that included 741 isolates of M. tuberculosis from patients. The isolates originated from 31 departments and were obtained by systematic surveillance between 1999 and 2012. Results In total 61.94% of the isolates were resistant to 1 or more drugs, and 147 isolates were MDR. In total, 170 genotypes were found in the population structure of Colombian M. tuberculosis isolates. The isolates were mainly represented by four families: LAM (39.9%), Haarlem (19%), Orphan (17%) and T (9%). The SIT42 (LAM 9) was the most common genotype and contained 24.7% of the isolates, followed by the genotypes SIT62 (Haarlem1), SIT53 (T1), and SIT50 (H3). A high clustering of isolates was evident with 79.8% of the isolates classified into 32 groups. The Beijing family was associated with resistant isolates, whereas the Haarlem and T families were associated with sensitive isolates. The Haarlem family was also associated with grouped isolates (p = 0.031). Conclusions A high proportion (approximately 80%) of isolates was found in clusters; these clusters were not associated with resistance to first-line drugs. The Beijing family was associated with drug resistance, whereas the T and Haarlem families were associated with susceptibility in the Colombian isolates studied. PMID:26066494

  1. Genetic diversity of Mycobacterium tuberculosis and transmission associated with first-line drug resistance: a first analysis in Jalisco, Mexico.

    Science.gov (United States)

    Lopez-Avalos, Gladys; Gonzalez-Palomar, Guadalupe; Lopez-Rodriguez, Martín; Vazquez-Chacon, Carlos Arturo; Mora-Aguilera, Gustavo; Gonzalez-Barrios, Juan Antonio; Villanueva-Arias, Juan Carlos; Sandoval-Diaz, Manuel; Miranda-Hernández, Ulises; Alvarez-Maya, Ikuri

    2017-12-01

    The objectives of this study were to analyse the frequency of gene mutations associated with antitubercular drug resistance in clinical samples from the population of Jalisco State (Mexico) and to evaluate the genetic variability of Mycobacterium tuberculosis and multidrug-resistant (MDR) M. tuberculosis strains to describe the frequency of various families. Clinical isolates of M. tuberculosis obtained from Jalisco State were analysed. Isolates were subjected to drug susceptibility testing, and mutations were characterised by sequencing, followed by genotyping using spoligotyping and mycobacterial interspersed repetitive units-variable-number of tandem repeats (MIRU-VNTR). Moreover, the prevalence of mutations was analysed by phylogenetic lineages. Resistant strains were analysed by sequencing of katG, inhA and rpoB genes to determine the presence of mutations associated with isoniazid and rifampicin resistance. In MDR, monoresistant and polyresistant isolates, mutations were found in 17 (54.84%) of 31 strains. Spoligotyping identified six different strain lineages [T1 (25.40%), H3 (7.94%), MANU (4.76%), X1 (3.17%), EAI5 (1.59%) and LAM1 (1.59%)], with the remaining strains identified as orphans. In additional tree-based identification, a dendrogram of spoligotype patterns generated five different similarity clusters. When combining 24-loci MIRU-VNTR and spoligotyping approaches, the results shows that there is no cluster formation, indicating low transmission of the samples. This study using spoligotyping and MIRU-VNTR showed that the analysed strains were not related to each other since no two identical strains were found. Families with the highest prevalence in the study were orphans followed by T family. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. A Variant PfCRT Isoform Can Contribute to Plasmodium falciparum Resistance to the First-Line Partner Drug Piperaquine

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    Satish K. Dhingra

    2017-05-01

    Full Text Available Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC90 or 50% parasite killing (50% lethal dose [LD50]. This mutation also reversed Dd2-mediated CQ resistance, sensitized parasites to amodiaquine, quinine, and artemisinin, and conferred amantadine and blasticidin resistance. Using heme fractionation assays, we demonstrate that PPQ causes a buildup of reactive free heme and inhibits the formation of chemically inert hemozoin crystals. Our data evoke inhibition of heme detoxification in the parasite’s acidic digestive vacuole as the primary mode of both the bis-aminoquinoline PPQ and the related 4-aminoquinoline CQ. Both drugs also inhibit hemoglobin proteolysis at elevated concentrations, suggesting an additional mode of action. Isogenic lines differing in their pfmdr1 copy number showed equivalent PPQ susceptibilities. We propose that mutations in PfCRT could contribute to a multifactorial basis of PPQ resistance in field isolates.

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

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    Li-li ZHANG

    2013-09-01

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

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

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    Zu Knyphausen, Fabia; Scheufele, Ramona; Kücherer, Claudia; Jansen, Klaus; Somogyi, Sybille; Dupke, Stephan; Jessen, Heiko; Schürmann, Dirk; Hamouda, Osamah; Meixenberger, Karolin; Bartmeyer, Barbara

    2014-01-01

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

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

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    Fabia Zu Knyphausen

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

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

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    Miriam Bobadilla-del Valle

    2015-09-01

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

  7. 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.

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    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.

  8. Triple Drug Combination of Zidovudine, Efavirenz and Lamivudine Loaded Lactoferrin Nanoparticles: an Effective Nano First-Line Regimen for HIV Therapy.

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    Kumar, Prashant; Lakshmi, Yeruva Samrajya; Kondapi, Anand K

    2017-02-01

    To enhance efficacy, bioavailability and reduce toxicity of first-line highly active anti-retroviral regimen, zidovudine + efavirenz + lamivudine loaded lactoferrin nanoparticles were prepared (FLART-NP) and characterized for physicochemical properties, bioactivity and pharmacokinetic profile. Nanoparticles were prepared using sol-oil protocol and characterized using different sources such as FE-SEM, AFM, NanoSight, and FT-IR. In-vitro and in-vivo studies have been done to access the encapsulation-efficiency, cellular localization, release kinetics, safety analysis, biodistribution and pharmacokinetics. FLART-NP with a mean diameter of 67 nm (FE-SEM) and an encapsulation efficiency of >58% for each drug were prepared. In-vitro studies suggest that FLART-NP deliver the maximum of its payload at pH5 with a minimum burst release throughout the study period with negligible toxicity to the erythrocytes plus improved in-vitro anti-HIV activity. FLART-NP has improved the in-vivo pharmacokinetics (PK) profiles over the free drugs; an average of >4fold increase in AUC and AUMC, 30% increase in the Cmax, >2fold in the half-life of each drug. Biodistribution data suggest that FLART-NP has improved the bioavailability of all drugs with less tissue-related inflammation as suggested with histopathological evaluation CONCLUSIONS: The triple-drug loaded nanoparticles have various advantages against soluble (free) drug combination in terms of enhanced bioavailability, improved PK profile and diminished drug-associated toxicity.

  9. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

    Science.gov (United States)

    Vandenhende, Marie-Anne; Bellecave, Pantxika; Recordon-Pinson, Patricia; Reigadas, Sandrine; Bidet, Yannick; Bruyand, Mathias; Bonnet, Fabrice; Lazaro, Estibaliz; Neau, Didier; Fleury, Hervé; Dabis, François; Morlat, Philippe; Masquelier, Bernard

    2014-01-01

    Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs) is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS) before antiretroviral therapy (ART) and at virological failure (VF), in HIV-1 infected patients experiencing VF on first-line ART. Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL) >500 copies/ml or one VL >1000 copies/ml) were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS) and UDS at baseline (before ART initiation) and VF. Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (p<0.0001) compared to SS. These low-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  10. Prevalence and evolution of low frequency HIV drug resistance mutations detected by ultra deep sequencing in patients experiencing first line antiretroviral therapy failure.

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    Marie-Anne Vandenhende

    Full Text Available OBJECTIVES: Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS before antiretroviral therapy (ART and at virological failure (VF, in HIV-1 infected patients experiencing VF on first-line ART. METHODS: Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL >500 copies/ml or one VL >1000 copies/ml were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS and UDS at baseline (before ART initiation and VF. RESULTS: Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (p<0.0001 compared to SS. These low-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. CONCLUSION: Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI.

  11. Adherence to drug-refill is a useful early warning indicator of virologic and immunologic failure among HIV patients on first-line ART in South Africa.

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    Ziad El-Khatib

    2011-03-01

    Full Text Available Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml and immunologic failure (as defined by WHO.After a median of 15 months on ART, 19% (n = 88 and 19% (n = 87 had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01. In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7, and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9, adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02.One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure.

  12. 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.

  13. Managing first-line failure

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    David A Cooper

    2014-11-01

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

  14. Managing first-line failure.

    Science.gov (United States)

    Cooper, David A

    2014-01-01

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

  15. Mechanisms of first-line antimicrobial resistance in multi-drug and extensively drug resistant strains of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa

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    Navisha Dookie

    2016-10-01

    Full Text Available Abstract Background In South Africa, drug resistant tuberculosis is a major public health crisis in the face of the colossal HIV pandemic. Methods In an attempt to understand the distribution of drug resistance in our setting, we analysed the rpoB, katG, inhA, pncA and embB genes associated with resistance to key drugs used in the treatment of tuberculosis in clinical isolates of Mycobacterium tuberculosis in the KwaZulu-Natal province. Results Classical mutations were detected in the katG, inhA and embB genes associated with resistance to isoniazid and ethambutol. Diverse mutations were recorded in the multidrug resistant (MDR and extensively drug resistant (XDR isolates for the rpoB and pncA gene associated with resistance to rifampicin and pyrazinamide. Conclusions M.tuberculosis strains circulating in our setting display a combination of previously observed mutations, each mediating resistance to a different drug. The MDR and XDR TB isolates analysed in this study displayed classical mutations linked to INH and EMB resistance, whilst diverse mutations were linked to RIF and PZA resistance. The similarity of the XDR strains confirms reports of the clonality of the XDR epidemic. The successful dissemination of the drug resistant strains in the province underscores the need for rapid diagnostics to effectively diagnose drug resistance and guide treatment.

  16. First line management in the public sector

    DEFF Research Database (Denmark)

    Voxted, Søren

    first-line managers’ work and to illuminate differences between first-line managers from different occupational groups. The second question relates to current debate about the degree of professionalized management among the municipal first-line managers. In both the international and Danish management......, in some examples, explicit standards are set for what share of the manager’s working time should be used on management and what share should be used on participation in operational tasks. The main question is how the division between exercising leadership and participating in operational task is evident......The paper will examines and discusses the results from a structured observational study, wherein 50 first-line managers from the public sector in Denmark in five areas of employment where observed. These observational studies are a key contribution in the ‘greenhouse for management’ project...

  17. Clinical practice format for choosing a second-line disease modifying anti-rheumatic drug in early rheumatoid arthritis after failure of 6 months' first-line DMARD therapy.

    Science.gov (United States)

    Meyer, Olivier; de Bandt, Michel; Berthelot, Jean-Marie; Cantagrel, Alain; Combe, Bernard; Fautrel, Bruno; Flipo, René-Marc; Lioté, Frédéric; Maillefert, Jean-Francis; Saraux, Alain; Wendling, Daniel; Guillemin, Francis; Le Loët, Xavier

    2007-01-01

    The objective was to develop a clinical practice format for choosing a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month course of a first-line DMARD in patients with early RA. A panel of 34 experts selected treatment option from various scenarios using the Thurstone pairwise method. The experts had to choose between two proposed DMARDs without proposing other options. The scenarios were obtained using the three items: DAS28, rheumatoid factor status and radiographic structural damage. A sample of 240 among 480 scenarios for each expert was taken at random. Responses given by at least 20% of the experts were considered pertinent. Recommendations for choosing a second DMARD for early RA after failure of a 6-month course of a first-line DMARD were established according to 4 parameters: type of first-line DMARD, activity, RF status and radiographic joint damage. The results of this study suggest that in patients with early RA who fail a 6-month course of first-line DMARD therapy, the best options may be addition of corticosteroid when disease activity is moderate to high and switching to a biologic agent when further radiographic joint damage occurs, particularly in patients with positive tests for RF. Although our scenarios did not include step-up (add instead of substitute) strategies, except for corticosteroids, we feel that the format presented here can optimise the management of patients with early RA seen in clinical practice.

  18. Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Goldberg, Lawrence D D; Edwards, Natalie C; Fincher, Contessa; Doan, Quan V; Al-Sabbagh, Ahmad; Meletiche, Dennis M

    2009-09-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered

  19. The Differential Gene Expression Pattern of Mycobacterium tuberculosis in Response to Capreomycin and PA-824 versus First-Line TB Drugs Reveals Stress- and PE/PPE-Related Drug Targets

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    Li M. Fu

    2009-01-01

    Full Text Available Tuberculosis is a leading infectious disease causing millions of deaths each year. How to eradicate mycobacterial persistence has become a central research focus for developing next-generation TB drugs. Yet, the knowledge in this area is fundamentally limited and only a few drugs, notably capreomycin and PA-824, have been shown to be active against non-replicating persistent TB bacilli. In this study, we performed a new bioinformatics analysis on microarray-based gene expression data obtained from the public domain to explore genes that were differentially induced by drugs between the group of capreomycin and PA-824 and the group of mainly the first-line TB drugs. Our study has identified 42 genes specifically induced by capreomycin and PA-824. Many of these genes are related to stress responses. In terms of the distribution of identified genes in a specific category relative to the whole genome, only the categories of PE/PPE and conserved hypotheticals have statistical significance. Six among the 42 genes identified in this study are on the list of the top 100 persistence targets selected by the TB Structural Genomics Consortium. Further biological elucidation of their roles in mycobacterial persistence is warranted.

  20. High prevalence of pfdhfr-pfdhps triple mutations associated with anti-malarial drugs resistance in Plasmodium falciparum isolates seven years after the adoption of sulfadoxine-pyrimethamine in combination with artesunate as first-line treatment in Iran.

    Science.gov (United States)

    Rouhani, Maryam; Zakeri, Sedigheh; Pirahmadi, Sakineh; Raeisi, Ahmad; Djadid, Navid Dinparast

    2015-04-01

    The spread of anti-malarial drug resistance will challenge any malaria control and elimination strategies, and routine monitoring of resistance-associated molecular markers of commonly used anti-malarial drugs is very important. Therefore, in the present investigation, the extent of mutations/haplotypes in dhfr and dhps genes of Plasmodium falciparum isolates (n=72) was analyzed seven years after the introduction of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) as first-line anti-malarial treatment in Iran using PCR-RFLP methods. The results showed that the majority of the patients (97.2%) carried both 59R and 108N mutations in pure form with wild-type genotype at positions N51 and I164. Additionally, a significant increase (Pdrug for treatment of falciparum patients in these malaria-endemic areas of Iran. However, no quintuple mutations associated with treatment failure were detected. In conclusion, the present results along with in vivo assays suggest that seven years after the adoption of SP-AS as the first-line treatment in Iran, this drug remains efficacious for treatment of uncomplicated falciparum malaria, as a partner drug with AS in these malaria-endemic areas. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Changes in first-line injectable disease-modifying therapy for multiple sclerosis: predictors of non-adherence, switching, discontinuation, and interruption of drugs.

    Science.gov (United States)

    Degli Esposti, Luca; Piccinni, Carlo; Sangiorgi, Diego; Perrone, Valentina; Aledda, Lucia; Marrosu, Maria Giovanna; Lombardo, Fabio

    2017-04-01

    This study was aimed to describe changes of Disease-Modifying Treatments (DMT) in an Italian cohort of patients with multiple sclerosis (MS) and to identify predictors of therapeutic modifications. Patients with MS and treated with the first-line injectable DMT (interferons-IFNs or glatiramer) between 1/7/2009 and 31/10/2012 were selected from administrative databases of the MS Center of Cagliari (Sardinia, Italy). Socio-demographic, therapeutic, and clinical information was collected in the 6 months preceding the index date. All patients were followed for 36 months to evaluate therapeutic changes in terms of non-adherence, switch, temporary discontinuation, and permanent interruption. Predictors of changes were estimated by multivariable regression models. Data on 1698 patients were collected: glatiramer was prescribed in 27% of cases, IFNβ-1b in 22%, IFNβ-1a-im in 20%, IFNβ-1a-sc-44mcg in 19%, and IFNβ-1a-sc-22mcg in 12%. Non-adherence was observed in 25% of cases, therapeutic switch in 30%, discontinuation in 37%, and permanent interruption in 28%. The risk of non-adherence was higher for IFNβ-1b, compared with IFNβ-1a-im (adjOR = 1.73). Therapeutic switch occurred especially in patients recently diagnosed (each year from diagnosis causes a decrease of this risk adjHR = 0.97); the risk of discontinuation was higher with EDSS = 4-6 and 7-9 (adjHR = 1.52 and 4.42, respectively). The risk of permanent interruption increased with the augmentation of disability (adjHR = 1.67 and 5.43 for EDSS 4-6 and 7-9). This study mirrored a detailed framework of DMT prescription and identified factors related to changes in the MS therapy. These findings could support healthcare providers in the evaluation and maximization of benefits associated with a long-term DMT.

  2. Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey.

    Science.gov (United States)

    Ávila-Ríos, Santiago; García-Morales, Claudia; Matías-Florentino, Margarita; Romero-Mora, Karla A; Tapia-Trejo, Daniela; Quiroz-Morales, Verónica S; Reyes-Gopar, Helena; Ji, Hezhao; Sandstrom, Paul; Casillas-Rodríguez, Jesús; Sierra-Madero, Juan; León-Juárez, Eddie A; Valenzuela-Lara, Marisol; Magis-Rodríguez, Carlos; Uribe-Zuñiga, Patricia; Reyes-Terán, Gustavo

    2016-12-01

    WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods. Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9·4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression. Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15·5%, 95% CI 11·4-20·5) had pretreatment resistance to any antiretroviral drug and 28 (10·6%, 7·2-15·0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score ≥15) was noted in 13 (4 · 9%) of participants to efavirenz and in 23 (8·7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14·4%, 95% CI 10·4-19·2) had pretreatment resistance to any antiretroviral drug and 26 (9·8%, 6·5

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

    Science.gov (United States)

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

    2017-09-22

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

  4. Determinants of immunological failure among clients on the first line treatment with highly active antiretroviral drugs in Dar es Salaam, Tanzania

    Directory of Open Access Journals (Sweden)

    Anthony Kapesa

    2014-07-01

    Conclusions: HAART-IF in Dar es Salaam is associated with ART programmatic and patients' centered challenges. There is a need to review the approaches on ensuring ART adherence, clients follow up and referral system so as to reduce the incidence of IF as we move to a more decentralized peripheral drug picks clinical initiative.

  5. Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case–control study using centralized ultrasensitive 454 pyrosequencing

    Science.gov (United States)

    Cozzi-Lepri, Alessandro; Noguera-Julian, Marc; Di Giallonardo, Francesca; Schuurman, Rob; Däumer, Martin; Aitken, Sue; Ceccherini-Silberstein, Francesca; D'Arminio Monforte, Antonella; Geretti, Anna Maria; Booth, Clare L.; Kaiser, Rolf; Michalik, Claudia; Jansen, Klaus; Masquelier, Bernard; Bellecave, Pantxika; Kouyos, Roger D.; Castro, Erika; Furrer, Hansjakob; Schultze, Anna; Günthard, Huldrych F.; Brun-Vezinet, Francoise; Paredes, Roger; Metzner, Karin J.; Paredes, Roger; Metzner, Karin J.; Cozzi-Lepri, Alessandro; Schuurman, Rob; Brun-Vezinet, Francoise; Günthard, Huldrych; Ceccherini-Silberstein, Francesca; Kaiser, Rolf; Geretti, Anna Maria; Brockmeyer, Norbert; Masquelier, Bernard; Dabis, F.; Bruyand, M.; Chêne, G.; Dabis, F.; Lawson-Ayayi, S.; Thiébaut, R.; Wittkop, L.; André, K.; Bonnal, F.; Bonnet, F.; Bernard, N.; Caunègre, L.; Cazanave, C.; Ceccaldi, J.; Chossat, I.; Courtaud, K.; Dauchy, F. A.; De Witte, S.; Dupon, M.; Dupont, A.; Duffau, P.; Dutronc, H.; Farbos, S.; Gaborieau, V.; Gemain, M. C.; Gerard, Y.; Greib, C.; Hessamfar, M.; Lacoste, D.; Lataste, P.; Lazaro, E.; Longy-Boursier, M.; Malvy, D.; Meraud, J. P.; Mercié, P.; Monlun, E.; Morlat, P.; Neau, D.; Ochoa, A.; Pellegrin, J. L.; Pistone, T.; Receveur, M. C.; Schmeltz, J. Roger; Tchamgoué, S.; Vandenhende, M. A.; Vareil, M.O.; Viallard, J. F.; Moreau, J. F.; Pellegrin, I.; Fleury, H.; Lafon, M. E.; Masquelier, B.; Reigadas, S.; Trimoulet, P.; Bouchet, S.; Breilh, D.; Molimard, M.; Titier, K.; Haramburu, F.; Miremont-Salamé., G.; Blaizeau, M. J.; Decoin, M.; Delaune, J.; Delveaux, S.; D'Ivernois, C.; Hanapier, C.; Leleux, O.; Lenaud, E.; Uwamaliya-Nziyumvira, B.; Sicard, X.; Geffard, S.; Le Marec, F.; Conte, V.; Frosch, A.; Leray, J.; Palmer, G.; Touchard, D.; Bonnet, F.; Breilh, D.; Chêne, G.; Dabis, F.; Dupon, M.; Fleury, H.; Malvy, D.; Mercié, P.; Morlat, P.; Neau, D.; Pellegrin, I.; Pellegrin, J. L.; Bouchet, S.; Gaborieau, V.; Lacoste, D.; Tchamgoué, S.; Thiébaut, R.; Losso, M.; Kundro, M.; Ramos Mejia, J. M.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J. P.; Girard, P. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Duvivier, C.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Bickel, M.; Bogner, J.; Fätkenheuer, G.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Sambatakou, H.; Banhegyi, D.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; HassounRambam, G.; Elinav, H.; HaouziHadassah, M.; EspositoI, R.; Mazzotta, F.; Vullo, V.; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Monforte, A. D'Arminio; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Antinori, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Puoti, M.; Quiros Roldan, E.; Rusconi, S.; Cozzi-Lepri, A.; Cicconi, P.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Carletti, F.; Carrara, S.; Castrogiovanni, A.; Di Caro, A.; Petrone, F.; Prota, G.; Quartu, S.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Vanino, E.; Verucchi, G.; Castelli, F.; Quiros Roldan, E.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Lo Caputo, S.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Bonfanti, P.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Puoti, M.; D'Arminio Monforte, A.; Ridolfo, A. L.; Piolini, R.; Castagna, A.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Marchetti, G.; Mussini, C.; Puzzolante, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Cauda, R.; Andreoni, M.; Antinori, A.; Vullo, V.; Cingolani, A.; d'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Sasset, L.; Mura, M. S.; Madeddu, G.; De Luca, A.; Rossetti, B.; Caramello, P.; Di Perri, G.; Orofino, G. C.; Bonora, S.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.; Brockmeyer, N. H.; Skaletz-Rorowski, A.; Dupke, S.; Baumgarten, A.; Carganico, A.; Köppe, S.; Kreckel, P.; Lauenroth-Mai, E.; Freiwald-Rausch, M.; Gölz, J.; Moll, A.; Zeitz, M.; Hower, M.; Reuter, S.; Jensen, B.; Harrer, T.; Esser, S.; Brodt, H. R.; Plettenberg, A.; Stöhr, A.; Buhk, T.; Stellbrink, H. J.; Stoll, M.; Schmidt, R.; Kuhlmann, B.; Mosthaf, F. A.; Rieke, A.; Becker, W.; Volkert, R.; Jäger, H.; Hartl, H.; Mutz, A.; Ulmer, A.; Müller, M.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Kouyos, R.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Staehelin, C.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

    2015-01-01

    Objectives It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. Methods This Europe-wide case–control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%–25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Results Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35–5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76–6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12–5.18, P = 0.024). A dose–effect relationship between virological failure and mutational load was found. Conclusions Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART. PMID:25336166

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

    Directory of Open Access Journals (Sweden)

    Daniele Armenia

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

  7. Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in Côte d'Ivoire

    Directory of Open Access Journals (Sweden)

    Offianan AT

    2011-11-01

    Full Text Available Andre T Offianan1, Serge B Assi2, Aristide MA Coulibaly1, Landry T N'guessan1, Aristide A Ako1, Florence K Kadjo2, Moïse K San2, Louis K Penali2 1Malariology Department, Institut Pasteur de Côte d'Ivoire, Abidjan, Côte d'Ivoire; 2National Malaria Control Programme, Abidjan, Côte d'Ivoire Background: The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. Artesunate + amodiaquine (ASAQ and artemether-lumefantrine (AL are respectively the first- and second-line treatments for uncomplicated falciparum malaria in Côte d'Ivoire. A comparison of the efficacy and safety of these two drug combinations was necessary to make evidence-based drug treatment policies. Methods: In an open-label, non inferiority, randomized, controlled clinical trial, children aged 6–59 months were randomized to receive ASAQ or AL. Both drug regimens were given for 3 days, and follow-up was for 28 days. The primary endpoint was the 28-day cure rates and was defined as proportion of patients with polymerase chain reaction (PCR-corrected cure rate after 28 days of follow-up. Findings: A total of 251 patients who were attending the Ayame and Dabakala hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive ASAQ (128 and AL (123. The intention-to-treat analysis showed effectiveness rates of 94.5% and 93.5% for ASAQ and AL, respectively on day 28. After adjustment for PCR results, these rates were 96.1% and 96.8%, respectively. On day 28, the per-protocol analysis showed effectiveness rates of 98.4% and 96.6% for ASAQ and AL, respectively. After adjustment by PCR for reinfection, these rates were 100% for each drug, and both regimens were well tolerated. Conclusion: ASAQ and AL remain efficacious treatments of uncomplicated falciparum malaria in Ivorian children 5 years after adoption. The efficacy of ASAQ and AL in Côte d'Ivoire requires, therefore, continuous

  8. Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis.

    Science.gov (United States)

    Upadhyay, Seema; Khan, Iliyas; Gothwal, Avinash; Pachouri, Praveen K; Bhaskar, N; Gupta, Umesh D; Chauhan, Devendra S; Gupta, Umesh

    2017-09-01

    First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and 1H-NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC's interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis. Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, -19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p HPMA-PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

  9. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.

    Science.gov (United States)

    Ventura, Andréa M C; Shieh, Huei Hsin; Bousso, Albert; Góes, Patrícia F; de Cássia F O Fernandes, Iracema; de Souza, Daniela C; Paulo, Rodrigo Locatelli Pedro; Chagas, Fabiana; Gilio, Alfredo E

    2015-11-01

    The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. PICU, Hospital Universitário da Universidade de São Paulo, Brazil. Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders. Patients were randomly assigned to receive either dopamine (5-10 μg/kg/min) or epinephrine (0.1-0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine. Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p=0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p=0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p=0.001). The use of epinephrine was associated with a survival odds ratio of 6.49. Dopamine was associated with an increased risk of death and healthcare

  10. High Rates of Transmission of Drug-resistant HIV in Aruba Resulting in Reduced Susceptibility to the WHO Recommended First-line Regimen in Nearly Half of Newly Diagnosed HIV-infected Patients.

    Science.gov (United States)

    Hofstra, L Marije; Sánchez Rivas, Elena; Nijhuis, Monique; Bank, Leonie E A; Wilkinson, Eduan; Kelly, Karina; Mudrikova, Tania; Schuurman, Rob; de Oliveira, Tulio; de Kort, Jaclyn; Wensing, Annemarie M J

    2017-04-15

    In Western countries emergence of human immunodeficiency virus (HIV) drug resistance has tremendously decreased, and transmission of drug resistance has merely stabilized in recent years. However, in many endemic settings with limited resources rates of emerging and transmitted drug resistance are not regularly assessed. We performed a survey including all HIV-infected individuals who received resistance testing in 2010-2015 in Aruba, a highly endemic HIV area in the Caribbean. Transmitted HIV drug resistance was determined using World Health Organization (WHO) criteria. Transmission dynamics were investigated using phylogenetic analyses. In a subset, baseline samples were re-analyzed using next generation sequencing (NGS). Baseline resistance testing was performed in 104 newly diagnosed untreated individuals (54% of all newly diagnosed individuals in 2010-2015): 86% were men, 39% were foreign-born, and 22% had AIDS at diagnosis. And 33% (95% CI: 24-42%) was infected with a drug-resistant HIV variant. The prevalence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) reached 45% (95% CI: 27-64%) in 2015, all based on the prevalence of mutation K103N. NGS did not demonstrate additional minority K103N-variants compared to routine resistance testing. K103N-harboring strains were introduced into the therapy-unexposed population via at least 6 independent transmissions epidemiologically linked to the surrounding countries. Virological failure of the WHO-recommended first-line NNRTI-based regimen was higher in the presence of K103N. The prevalence of resistant HIV in Aruba has increased to alarming levels, compromising the WHO-recommended first-line regimen. As adequate surveillance as advocated by the WHO is limited, the Caribbean region could face an unidentified rise of NNRTI-resistant HIV.

  11. Usage and cost of first-line drugs for patients referred to inpatient anthroposophic integrative care or inpatient conventional care for stress-related mental disorders--a register based study.

    Science.gov (United States)

    Sundberg, Tobias; Hussain-Alkhateeb, Laith; Falkenberg, Torkel

    2015-10-14

    Stress-related mental disorders (SRMD) are common and costly. Rehabilitation strategies, including pharmacotherapy, may be complicated to evaluate. Previous research has indicated increased quality of life and self-rated health for SRMD patients that receive a combination of conventional and complementary therapies, i.e. integrative care. The aim of this retrospective registry study was to explore and contrast the prescription of first-line drugs for SRMD patients referred to hospital inpatient anthroposophic integrative care (AIC) or inpatient conventional care (CC). SRMD patients that had received AIC or CC were identified through high-quality inpatient registry data from Stockholm County Council and matched by available background characteristics including diagnosis (ICD-10: F43), age, gender and socio-economics. General disease load was estimated by analysis of ICD-10 chapter data. The Swedish Prescribed Drug Register was then used to investigate purchased defined daily doses (DDD) and cost of drugs from 90-days before/after, and 180-days before/after, the first visits (index) to AIC and CC respectively. First-line drug categories were Anatomical Therapeutic Chemical classification codes N05A (antipsychotics), N05B (anxiolytics), N05C (hypnotics and sedatives) and N06A (antidepressants). There were no statistically significant differences between the AIC (n = 161) and the CC (n = 1571) cohorts in terms of background characteristics and the overall disease loads were similar between the groups the preceding year. At baseline, the prescription of first-line anxiolytics and antidepressants were not statistically different between groups whereas the prescription of antipsychotics and hypnotics/sedatives were lower for the AIC cohort. The overall change in drug prescriptions and costs during the investigated periods, both for the 90-days before/after and for the 180-days before/after the index visit, showed a general decrease within the AIC cohort with

  12. Pharmaceutical technology can turn a traditional drug, dexamethasone into a first-line ocular medicine. A global perspective and future trends.

    Science.gov (United States)

    Rodríguez Villanueva, Javier; Rodríguez Villanueva, Laura; Guzmán Navarro, Manuel

    2017-01-10

    Dexamethasone is one of the most prescribed glucocorticoids. It is effective and safe in the treatment of a wide variety of ocular conditions, including anterior and posterior segment inflammation. However, its half-life in the vitreous humor is very short, which means that it typically requires frequent administrations, thus reducing patient adherence and causing therapeutic failure. Innovative dexamethasone delivery systems have been designed in an attempt to achieve sustained release and targeting. The FDA has approved dexamethasone implants for the treatment of macular edema secondary to retinal vein occlusion and posterior segment noninfectious uveitis. Lenses, micro- and nanoparticles, liposomes, micelles and dendrimers are also proving to be adequate systems for maintaining optimal dexamethasone levels in the site of action. Pharmaceutical technology is turning a classical drug, dexamethasone, into a fashionable medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia.

    Science.gov (United States)

    Wisaksana, Rudi; Indrati, Agnes K; Fibriani, Azzania; Rogayah, Ega; Sudjana, Primal; Djajakusumah, Tony S; Sumantri, Rachmat; Alisjahbana, Bachti; van der Ven, Andre; van Crevel, Reinout

    2010-06-01

    There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan-Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12-111] cells/mm(3) compared to 84 (IQR, 28-224) cells/mm(3) in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts or =200/mm(3) had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35-1.23], loss to follow-up (HR = 0.85, 95% CI 0.51-1.41) and virological failure (HR = 0.47, 95% CI 0.19-1.13) were not significantly different in IDUs and non-IDUs. Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy.

  14. How sulfadoxine-pyrimethamine (SP was perceived in some rural communities after phasing out chloroquine (CQ as a first-line drug for uncomplicated malaria in Tanzania: lessons to learn towards moving from monotherapy to fixed combination therapy

    Directory of Open Access Journals (Sweden)

    Nsimba Stephen ED

    2006-01-01

    Full Text Available Abstract Malaria is a leading cause of death in Sub-Saharan Africa. Tanzania changed its malaria treatment policy from chloroquine (CQ to Sulphadoxine-Pyrimethamine (SP as first line drug in August 2001. We wanted to assess the perception and behaviour about SP after phasing out chloroquine which was very popular, cheap, available, and was preferred by many people for self-medication in homes as it was considered to have minimal side effects. Focus Group Discussions (FGDs were carried out after one year of the anti-malarial drug treatment policy change in the country. The FGD themes were on malaria for under-five children and other age groups, anti-malarial drug use through self-medications, specific experiences people had about SP drug for both mothers/guardians, men in the communities and health workers. A total of twelve FGDs were performed with mothers/guardians, men and health workers in the selected public health care facilities in the district. In the FGDs people feared adverse reactions from SP; its slow ability of reducing fever and self-treatment in this case was less reported from the mothers/guardians groups. However, SP was reported by health workers to be administered using the direct observation approach under supervision in their health care facilities. This was done in order to increase compliance as there were worries that some mothers were throwing away the drug if they were instructed by health workers to go and administer SP to their sick children at home. Based on this information, it is obvious that fear and negative perceptions about SP drug was common in the study setting. As evidence of this, there was less reported home-stocking and self-medication in the discussions for this particular recommended new first-line anti-malarial. The public has demonstrated a lack of confidence in SP. Furthermore, some health workers expressed obvious fear and negative perceptions towards the drug despite the fact that some FGDs with

  15. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis.

    Science.gov (United States)

    Gupta, Ravindra K; Gregson, John; Parkin, Neil; Haile-Selassie, Hiwot; Tanuri, Amilcar; Andrade Forero, Liliana; Kaleebu, Pontiano; Watera, Christine; Aghokeng, Avelin; Mutenda, Nicholus; Dzangare, Janet; Hone, San; Hang, Zaw Zaw; Garcia, Judith; Garcia, Zully; Marchorro, Paola; Beteta, Enrique; Giron, Amalia; Hamers, Raph; Inzaule, Seth; Frenkel, Lisa M; Chung, Michael H; de Oliveira, Tulio; Pillay, Deenan; Naidoo, Kogie; Kharsany, Ayesha; Kugathasan, Ruthiran; Cutino, Teresa; Hunt, Gillian; Avila Rios, Santiago; Doherty, Meg; Jordan, Michael R; Bertagnolio, Silvia

    2017-12-05

    Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs. This study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions. We identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5-15·9) in southern Africa, 10·1% (5·1-19·4) in eastern Africa, 7·2% (2·9-16·5) in western and central Africa, and 9·4% (6·6-13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly

  16. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Chen JH

    2016-04-01

    Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

  17. Selective Internal Radiation Therapy (SIRT) with yttrium-90 resin microspheres plus standard systemic chemotherapy regimen of FOLFOX versus FOLFOX alone as first-line treatment of non-resectable liver metastases from colorectal cancer: the SIRFLOX study.

    Science.gov (United States)

    Gibbs, Peter; Gebski, Val; Van Buskirk, Mark; Thurston, Kenneth; Cade, David N; Van Hazel, Guy A

    2014-12-01

    In colorectal cancer (CRC), unresectable liver metastases are linked to poor prognosis. Systemic chemotherapy with regimens such as FOLFOX (combination of infusional 5-fluorouracil, leucovorin and oxaliplatin) is the standard first-line treatment. The SIRFLOX trial was designed to assess the efficacy and safety of combining FOLFOX-based chemotherapy with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-SpheresR; Sirtex Medical Limited, North Sydney, Australia). SIRFLOX is a randomised, multicentre trial of mFOLFOX6 chemotherapy+/-SIRT as first-line treatment of patients with liver-only or liver-predominant metastatic CRC (mCRC). The trial aims to recruit adult chemotherapy-naive patients with proven liver metastases with or without limited extra-hepatic disease, a life expectancy of >=3 months and a WHO performance status of 0-1. Patients will be randomised to receive either mFOLFOX6 or SIRT+mFOLFOX6 (with a reduced dose of oxaliplatin in cycles 1-3 following SIRT). Patients in both arms can receive bevacizumab at investigator discretion. Protocol chemotherapy will continue until there is unacceptable toxicity, evidence of tumour progression, complete surgical resection or ablation of cancerous lesions, or the patient requests an end to treatment. The primary endpoint of the SIRFLOX trial is progression-free survival (PFS). Secondary endpoints include: PFS in the liver; tumour response rate (liver and any site); site of tumour progression; health-related quality of life; toxicity and safety; liver resection rate; and overall survival. Assuming an increase in the median PFS from 9.4 months to 12.5 months with the addition of SIRT to mFOLFOX6, recruiting >=450 patients will be sufficient for 80% power and 95% confidence. The SIRFLOX trial will establish the potential role of SIRT+standard systemic chemotherapy in the first-line management of mCRC with non-resectable liver metastases. SIRFLOX Clinical

  18. Prospective evaluation of [11C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer.

    Science.gov (United States)

    Schwarzenböck, Sarah M; Eiber, Matthias; Kundt, Günther; Retz, Margitta; Sakretz, Monique; Kurth, Jens; Treiber, Uwe; Nawroth, Roman; Rummeny, Ernst J; Gschwend, Jürgen E; Schwaiger, Markus; Thalgott, Mark; Krause, Bernd J

    2016-11-01

    The aim of this study was to prospectively evaluate the value of [11C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [11C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [11C] Choline uptake (SUVmax, SUVmean), CT derived Houndsfield units (HUmax, HUmean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUVmax, SUVmean, HUmax, HUmean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUVmax and SUVmean (early and late) and changes of PSAearly and PSAlate were evaluated. Prognostic value of initial SUVmax and SUVmean was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUVmax and SUVmean were statistically significantly higher in nPD (applying clinical criteria). There is no

  19. Prospective evaluation of [{sup 11}C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenboeck, Sarah M.; Krause, Bernd J. [Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Rostock University Medical Centre, Department of Nuclear Medicine, Rostock (Germany); Eiber, Matthias; Schwaiger, Markus [Technical University of Munich, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kundt, Guenther [Rostock University Medical Centre, Department of Biostatistics and Informatics, Rostock (Germany); Retz, Margitta; Treiber, Uwe; Nawroth, Roman; Gschwend, Juergen E.; Thalgott, Mark [Technical University of Munich, Department of Urology, Klinikum rechts der Isar, Munich (Germany); Sakretz, Monique; Kurth, Jens [Rostock University Medical Centre, Department of Nuclear Medicine, Rostock (Germany); Rummeny, Ernst J. [Technical University of Munich, Institute of Radiology, Klinikum rechts der Isar, Munich (Germany)

    2016-11-15

    The aim of this study was to prospectively evaluate the value of [{sup 11}C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients. Thirty-two patients were referred for [{sup 11}C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [{sup 11}C] Choline uptake (SUV{sub max}, SUV{sub mean}), CT derived Houndsfield units (HU{sub max}, HU{sub mean}), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV{sub max}, SUV{sub mean}, HU{sub max}, HU{sub mean,} and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV{sub max} and SUV{sub mean} (early and late) and changes of PSA{sub early} and PSA{sub late} were evaluated. Prognostic value of initial SUV{sub max} and SUV{sub mean} was assessed. Statistical analyses were performed using SPSS. In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV{sub max

  20. Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group

    Science.gov (United States)

    Ray-Coquard, I; Paraiso, D; Guastalla, J-P; Leduc, B; Guichard, F; Martin, C; Chauvenet, L; Haddad-Guichard, Z; Lepillé, D; Orfeuvre, H; Gautier, H; Castera, D; Pujade-Lauraine, É

    2007-01-01

    ICON3 trial results have suggested that CAP and carboplatin–taxol regimens as first-line treatment of advanced ovarian cancer (AOC) yield similar survival. We explored the impact of increased dose of cyclophosphamide in a modified CAP regimen on the disease-free survival (DFS) and overall survival (OS) of AOC patients. From February 1994 to June 1997, 164 patients were randomised to receive six cycles every 3 weeks of either standard CEP (S) combining cyclophosphamide (C), 500 mg m−2, epirubicin (E) 50 mg m−2, and cisplatin (P) 75 mg m−2 or intensive CEP (I) with E and P at the same doses, but with (C) 1800 mg m−2 and filgrastim 5 μg kg−1 per day × 10 days. Response was evaluated at second-look surgery. Patient characteristics were well balanced. Except for grade 3–4 neutropaenia (S: 54%, I: 38% of cycles), Arm1 presented a significantly more important toxicity: infection requiring antibiotics, grade 3–4 thrombocytopaenia, anaemia, nausea-vomiting, diarrhoea, mucositis. Median follow-up was 84 months. DFS (15.9 vs 14.8 months) and OS (33 vs 30 months) were not significantly different between S and I (P>0.05). Increasing cyclophosphamide dose by more than 3 times with filgrastim support in the modified CAP regimen CEP induces more toxicity but not better efficacy in AOC. PMID:17923867

  1. Adherence to On-Time ART Drug Pick-Up and Its Association with CD4 Changes and Clinical Outcomes Amongst HIV Infected Adults on First-Line Antiretroviral Therapy in Nigerian Hospitals.

    Science.gov (United States)

    Anoje, Chukwuemeka; Agu, Kenneth Anene; Oladele, Edward A; Badru, Titilope; Adedokun, Oluwasanmi; Oqua, Dorothy; Khamofu, Hadiza; Adebayo, Olufunso; Torpey, Kwasi; Chabikuli, Otto Nzapfurundi

    2017-02-01

    Medication adherence is a major determinant of antiretroviral treatment (ART) success. Promptness in medication refill pick-ups may give an indication of medication adherence. This study determined medication refill adherence among HIV positive patients on ART and its association with treatment outcomes in HIV treatment centers in Nigeria. This retrospective multi-center cohort study involved a review of ART refill records for 3534 HIV-positive patients aged 18-60 years who initiated first-line ART between January 2008 and December 2009 and were on therapy for ≥18 months after ART initiation. Drug refill records of these patients for 10 consecutive refill visits after ART initiation were analyzed. The first ten consecutive refill appointment-keeping rates after ART initiation ranged from 64.3 % to 76.1 % which decreased with successive visits. Altogether, 743 (21.1 %) patients were deemed adherent, meaning they picked up their drugs within 7 days of the drug refill appointment date on at least nine out of ten refill visits. The adherent group of patients had a mean CD4 cells increase of 206 ± 6.1 cells/dl after 12 months of ART compared to 186 ± 7.1 cells/dl reported among the nonadherent group (p = 0.0145). The proportion of patients in the adherent category who showed no OIs after 12 months on ART (81 %) was significantly higher when compared to the proportion in the non-adherent category (23.5 %), (p = 0.008). The multivariate analysis showed that the odds of being adherent was 2-3 times more in patients who had a baseline CD4 count of less than 200 cells/dl compared to those with a baseline CD4 of >350 cells/dl. (AOR 2.43, 95 % CI 1.62-3.66). In addition, for patients with baseline CD4 cell count of 201-350 cells/dl, the odds of being adherent was found to be 1.9 compared to those with baseline CD4 of greater than 350 cells/dl (AOR 1.93, 95 % CI 1.27-2.94). Pharmacy refill data can serve as an adherence measure. Adherence to on-time drug

  2. The incidence of first-line antiretroviral treatment changes and ...

    African Journals Online (AJOL)

    The review included records of HIV-infected patients aged ≥ 18 years, who received either stavudine or zidovudine or tenofovir disoproxil fumarate-based regimens. Using systematic random sampling, the study selected 1 500 records and censoring targeted the first incident of a drug change from the first-line cART.

  3. Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination with First Line Anti-Tuberculosis Drugs, against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its Multi-Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Leonard Amaral

    2017-01-01

    Full Text Available This review presents the evidence that supports the use of thioridazine (TZ for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR Mtb. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.

  4. Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination with First Line Anti-Tuberculosis Drugs, against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its Multi-Mechanisms of Action.

    Science.gov (United States)

    Amaral, Leonard; Viveiros, Miguel

    2017-01-14

    This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.

  5. Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination with First Line Anti-Tuberculosis Drugs, against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its Multi-Mechanisms of Action

    OpenAIRE

    Leonard Amaral; Miguel Viveiros

    2017-01-01

    This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infecte...

  6. Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha Antituberculosis drugs: drug interactions, adverse effects, and use in special situations - part 1: first-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. Revisamos sucintamente o novo tratamento farmacológico da tuberculose introduzido pelo Ministério da Saúde do Brasil em 2009 e mostramos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no esquema básico. 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. Também descrevemos os mecanismos pelos quais as interações das drogas antituberculose do esquema básico podem causar hepatite medicamentosa e as possíveis alternativas nessa situação.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 briefly review the new guidelines for the pharmacological treatment of tuberculosis, introduced by the Brazilian National Ministry of Health in 2009, and describe the general mechanism of action, absorption, metabolization, and excretion of the first-line drugs used in the basic regimen. 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. We also describe the mechanisms by which the interactions among the antituberculosis drugs used in the basic regimen

  7. Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer.

    Science.gov (United States)

    Yamaue, Hiroki; Shimizu, Atsushi; Hagiwara, Yasuhiro; Sho, Masayuki; Yanagimoto, Hiroaki; Nakamori, Shoji; Ueno, Hideki; Ishii, Hiroshi; Kitano, Masayuki; Sugimori, Kazuya; Maguchi, Hiroyuki; Ohkawa, Shinichi; Imaoka, Hiroshi; Hashimoto, Daisuke; Ueda, Kazuki; Nebiki, Hiroko; Nagakawa, Tatsuya; Isayama, Hiroyuki; Yokota, Isao; Ohashi, Yasuo; Shirasaka, Tetsuhiko

    2017-04-01

    Non-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604). Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety. A total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20-2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment. S-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.

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

    Directory of Open Access Journals (Sweden)

    Rafiyath Shamudheen

    2010-11-01

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

  9. An open-label safety study of first-line bevacizumab in combination with standard chemotherapy in Chinese patients with metastatic colorectal cancer treated in an expanded access program in Taiwan.

    Science.gov (United States)

    Lee, Kuan-Der; Chen, Hong-Hwa; Wang, Hwei-Ming; Tsao, Chao-Jung; Hsu, Tzu-Chi; Chiu, Chang-Fang; Su, Wu-Chou; Wang, Jeng-Yi

    2013-01-01

    An increased risk of serious adverse effects related to bevacizumab has been observed in many Western studies for metastatic colorectal cancer. To evaluate the safety of bevacizumab in Chinese patients, a safety study was conducted in Taiwan. Bevacizumab was provided by the Expanded Access Program in combination with first-line chemotherapy per investigator's choice. The primary objective is the safety profile, particularly the targeted adverse events such as proteinuria, bowel perforation, hypertension, wound healing complication, thromboembolism and bleeding. The second objectives include time to disease progression and overall survival time. Patients with major surgical procedure performed within the 28 days of bevacizumab were excluded from this study. Forty patients were eligible for intent-to-treat analysis. The overall rate of objective response and disease control was 55.2 and 81.6%. The median time to disease progression and overall survival were 11.9 and 22.9 months. The actuarial 2-year survival was 46.6%. Regarding toxicity, 7 subjects (17.5%) had serious adverse effects related to study treatment. None of the patients in this cohort had arterial thrombotic events and bowel perforation. Bevacizumab demonstrates a similar activity and safety profile in Chinese patients. Life-threatening bowel complications were avoided in this study by excluding patients with major surgery within the first 28 days. Copyright © 2013 S. Karger AG, Basel.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    for isoniazid, rifampin, and ethambutol. Fifty-seven of the isolates were tested for pyrazinamide. Results were compared to those of radiometric BACTEC 460 system and discrepancies were resolved by the agar proportion method. We found an overall agreement of 99.0% for isoniazid, 99.5% for rifampin, 98.......2% for ethambutol, and 100% for pyrazinamide. After resolution of discrepancies, MGIT yielded no false susceptibility for rifampin and isoniazid. Although turnaround times were comparable, MGIT provides an advantage as inoculation can be done on any weekday as the growth is monitored automatically. The automated...

  11. The First-Line Supervisor: Literature Review

    Science.gov (United States)

    1984-01-01

    form (because of the presumably adverse effects upon the principle of unity of command), Taylor’s writings, along with those of Fayol , Mooney, Urwick...Journal of Business of the University of Chicago, 1957, 30, 202-211. Taylor, F. W. The principles of scientific management . New York: Harper and...mry and Idontlty by block numbor) Supervisor First-line supervisor Foreman Leadership Management 20. ABSTRACT (Contlnu» on r»v»r»» »Id» II

  12. Flecainide as first-line treatment for fetal supraventricular tachycardia.

    Science.gov (United States)

    Ekiz, Ali; Kaya, Basak; Bornaun, Helen; Acar, Deniz Kanber; Avci, Muhittin Eftal; Bestel, Aysegul; Yildirim, Gokhan

    2018-02-01

    The aim of this study was to evaluate utilization, efficacy, and side effects of flecainide treatment as first-line agent in patients with fetal supraventricular tachycardia (SVT). This retrospective review was conducted on 23 consecutive fetal tachyarrhythmia cases that met inclusion criteria. If the treatment was necessary, then flecainide was used as first-line treatment in all cases. Among the study group, there were 21 (91.3%) cases of SVT and 2 (8.6%) cases of Atrial Flutter (AF). Sixteen fetuses had persistent SVT and five fetuses had intermittent SVT. We treated 17 fetuses with flecainide monotherapy and 15 of them converted to sinus rhythm and remaining two fetuses were refractory to monotherapy. The median time to conversion to sinus rhythm was 3.8 ± 1.6 days. Only one fetus (20%) among the intermittent SVT cases required anti-arrhythmic treatment. Our study has demonstrated that flecainide is an effective first-line treatment for fetal SVT with high success rate (88.2%), low side effect profile and relatively easy utilization. Based on the current study and recently published article results, flecainide can be recommended as the drug of first choice for treatment of fetal SVT cases.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International m...

  14. Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Nielsen, Jens Cosedis; Johannessen, Arne; Raatikainen, Pekka

    2016-01-01

    OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint...

  15. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

    NARCIS (Netherlands)

    Gupta, Ravindra K.; Gregson, John; Parkin, Neil; Haile-Selassie, Hiwot; Tanuri, Amilcar; Andrade Forero, Liliana; Kaleebu, Pontiano; Watera, Christine; Aghokeng, Avelin; Mutenda, Nicholus; Dzangare, Janet; Hone, San; Hang, Zaw Zaw; Garcia, Judith; Garcia, Zully; Marchorro, Paola; Beteta, Enrique; Giron, Amalia; Hamers, Raph; Inzaule, Seth; Frenkel, Lisa M.; Chung, Michael H.; de Oliveira, Tulio; Pillay, Deenan; Naidoo, Kogie; Kharsany, Ayesha; Kugathasan, Ruthiran; Cutino, Teresa; Hunt, Gillian; Avila Rios, Santiago; Doherty, Meg; Jordan, Michael R.; Bertagnolio, Silvia

    2017-01-01

    Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether

  16. Standardization Study of Antifertility Drug - Pippalyadiyoga

    Directory of Open Access Journals (Sweden)

    D. Shaila

    2005-01-01

    Full Text Available The present paper deals with the standardization study of pippalyadiyoga powder. It is used as a long acting contraceptive. The standardization of compound drug has been achieved by physico-chemical analysis and high performance liquid chromatography (HPLC fingerprint studies. Quantitative evaluation of borax in pippalyadiyoga showed 19.08% as sodium borate. RP-HPLC was performed using methanol and water as mobile phase. The detection and quantification was performed at a wavelength of 345 nm. Linearity of detector response for piperine was between the concentrations 0.005% to 0.1%. The correlation coefficient obtained for the linearity was 0.998. The recovery value of standard piperine was 99.4%. Low value of standard deviation and coefficient of variation are indicative of high precision of the method. Quantitative evaluation of piperine in pippalyadiyoga was found to be 0.339%.

  17. Triple therapy versus sequential therapy for the first-line Helicobacter pylori eradication.

    Science.gov (United States)

    Chang, Ji Young; Shim, Ki-Nam; Tae, Chung Hyun; Lee, Ko Eun; Lee, Jihyun; Lee, Kang Hoon; Moon, Chang Mo; Kim, Seong-Eun; Jung, Hye-Kyung; Jung, Sung-Ae

    2017-01-21

    The eradication rate of Helicobacter pylori (H. pylori) with triple therapy which was considered as standard first-line treatment has decreased to 70-85%. The aim of this study is to compare 7-day triple therapy versus 10-day sequential therapy as the first line treatment. Data of 1240 H. pylori positive patients treated with triple therapy or sequential therapy from January 2013 to December 2015 were analyzed retrospectively. The patients who had undertaken previous H. pylori eradication therapy or gastric surgery were excluded. There were 872 (74.3%) patients in the triple therapy group, and 302 (25.7%) patients in the sequential therapy group. There was no significant difference between the two groups regarding age, residence, comorbidities or drug compliance, but several differences were noted in endoscopic characteristics and indication for the treatment. The eradication rate of H. pylori by intention to treat analysis was 64.3% in the triple therapy group, and 81.9% in the sequential therapy group (P = 0.001). In per protocol analysis, H. pylori eradication rate in the triple therapy and sequential therapy group was 81.9 and 90.3%, respectively (P = 0.002). There was no significant difference in overall adverse events between the two groups (P = 0.706). For the rescue therapy, bismuth-containing quadruple therapy showed comparable treatment efficacy after sequential therapy, as following triple therapy. The eradication rate of triple therapy was below the recommended threshold. Sequential therapy could be effective and tolerable candidate for the first-line H. pylori eradication therapy.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. Meryem Aitelhaj, Siham Lkhoyaali, Ghizlane Rais, Saber Boutayeb, Hassan Errihani ...

  20. HELOISE: Phase IIIb Randomized Multicenter Study Comparing Standard-of-Care and Higher-Dose Trastuzumab Regimens Combined With Chemotherapy as First-Line Therapy in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma.

    Science.gov (United States)

    Shah, Manish A; Xu, Rui-Hua; Bang, Yung-Jue; Hoff, Paulo M; Liu, Tianshu; Herráez-Baranda, Luis A; Xia, Fan; Garg, Amit; Shing, Mona; Tabernero, Josep

    2017-08-01

    Purpose To compare standard-of-care (SoC) trastuzumab plus chemotherapy with higher-dose (HD) trastuzumab plus chemotherapy to investigate whether HD trastuzumab increases trastuzumab serum trough concentration (Ctrough) levels and increases overall survival (OS) in first-line human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. Patients and Methods Patients with Eastern Cooperative Oncology Group performance status 2, no prior gastrectomy, and ≥ two metastatic sites were randomly assigned at a one-to-one ratio to loading-dose trastuzumab 8 mg/kg followed by SoC trastuzumab maintenance 6 mg/kg every 3 weeks or loading-dose trastuzumab 8 mg/kg followed by HD trastuzumab maintenance 10 mg/kg every 3 weeks until progression; treatment in each arm was combined with cisplatin 80 mg/m(2) plus capecitabine 800 mg/m(2) twice per day in cycles 1 to 6. The primary objective was HD trastuzumab OS superiority (all randomly assigned patients [full-analysis set]). Final results are from an interim analysis for futility (boundary hazard ratio [HR] ≥ 0.95) at 125 deaths. Results At clinical cutoff, 248 patients had been randomly assigned. A marked increase in mean trastuzumab Ctrough was observed after the first HD trastuzumab cycle versus SoC trastuzumab. In the full-analysis set, median OS was 12.5 months in the SoC trastuzumab arm and 10.6 months in the HD trastuzumab arm (stratified HR, 1.24; 95% CI, 0.86 to 1.78; P = .2401). Results were similar in the per-protocol set (cycle 1 trastuzumab Ctrough trastuzumab maintenance dosing was associated with higher trastuzumab concentrations, no increased efficacy, and no new safety signals. HELOISE confirms standard-dose trastuzumab (loading dose of 8 mg/kg followed by 6 mg/kg maintenance dose every 3 weeks) with chemotherapy as the SoC for first-line treatment of human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction

  1. Should capecitabine replace 5-fluorouracil in the first-line treatment of metastatic colorectal cancer?

    Science.gov (United States)

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

    2014-01-01

    Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient alternative to 5-fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either as a monotherapy or in combination with oxaliplatin, irinotecan, or biological drugs-and has been found to have comparable efficacy and safety profiles. Furthermore, pharmacoeconomic data and patients’ preferences for oral chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an effective and safe alternative to fluorouracil in the first-line treatment of metastatic colorectal cancer. PMID:24876731

  2. A first-line nurse manager's goal-profile.

    Science.gov (United States)

    Johansson, Gunilla; Pörn, Ingmar; Theorell, Töres; Gustafsson, Barbro

    2007-01-01

    The aim of this case study was to acquire understanding concerning the first-line nurse manager's goal-profile, i.e. prioritization of goals in her work as a first-line nurse manager, through use of an action-theoretic and confirmatory theory. The first-line nurse manager's pivotal role regarding quality of care and development in relation to on-going changes in the health care sector is stressed by many researchers and the transition from nurse to manager is described as a demanding challenge for the first-line nurse manager. The case study described in this paper concerns a first-line nurse manager in an actual working environment in care of older people. Data collection comprised interviews, observations, a job description and policy documents. A hermeneutic interpretation was used for data analysis. The results showed that the first-line nurse manager had three goals in her goal-profile, in the following order of priority: (i) a nurse goal that she had strongly accepted and in which she had excellent control, (ii) an administrator goal that she had accepted and in which she had control, (iii) a leadership goal that she had not accepted and in which she did not have control. Both the administrator and leadership goals were based on her job description, but the nurse goal was a personally chosen goal based on her own self-relation/goal-fulfillment. The first-line nurse manager's prioritized self-identity, based on successful realization of goals in her goal-profile, was decisive in the manifestation of her work. This study contributes to a new understanding of the first-line nurse manager's self-identity related to work in terms of goal acceptance and goal control of prioritized goals. This action-theoretic approach could be a valuable 'key' for understanding leadership (or lack of leadership) in clinical practice.

  3. DETERMINACIÓN DE LA SUSCEPTIBILIDAD A DROGAS DE PRIMERA LÍNEA EN AISLAMIENTOS DE MYCOBACTERIUM TUBERCULOSIS POR LA TÉCNICA DEL TUBO INDICADOR DE CRECIMIENTO MICOBACTERIANO Determining the susceptibility to first-line drugs in M. tuberculosis isolates using the mycobacteria growth indicator tube method

    Directory of Open Access Journals (Sweden)

    Claudia Rocío Sierra Parada

    2008-03-01

    etambutol.Background. The appearance of Mycobacterium tuberculosis isolates resistant to drugs has triggered the search for quicker and more reliable methods to determine the susceptibility to anti-tuberculosis drugs. Objective. To evaluate the susceptibility of M. tuberculosis isolates to anti-tuberculosis first line drugs by Mycobacterium growth indicator tube method (MGIT. Materials and methods. Forty-nine isolates of M. tuberculosis were tested, coming from the Mycobacteriology Laboratory of Microbiology Department of the Universidad Nacional de Colombia. The MGIT method was evaluated and compared in order to determine resistance or susceptibility to rifampicin, isoniazid, ethambutol and streptomycin with the gold standard method, the multiple proportion method (PM. Results. With the PM method, of 49 isolates, 26 (53.0% were sensitive to all four antibiotics, 12 (24.5% were resistant to one antibiotic and 11 (22.5% to more than one antibiotic. Using the MGIT method, of 49 isolates, 31 (63.3% were sensitive to all four antibiotics, 8 (16.3% were resistant to one antibiotic and 10 (20.6% were resistant to more than one antibiotic. The concordance percentages observed oscillated between 83.7% and 97.9% and the kappa index was between 0.61 and 0.83 for the different antibiotics analyzed. The sensitivity of the MGIT method to the rifampicin, isoniazid, ethambutol and streptomycin was of 88.9, 95.2, 62.5 and 58% respectively and specifity was of 97.7, 92.3, 98.8 y 98.4% respectively. Using the MGIT method, isolates resistant to M. tuberculosis were determined in an average time of 7.85 days. Conclusions. The MGIT method permits obtaining reliable results in less time than conventional methods with isoniazid and rifampicin which are the antibiotics that determine the multi-resistance of M tuberculosis and to a lesser degree to streptomycin and ethambutol.

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

    Science.gov (United States)

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

    2017-09-01

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

  5. Nanomaterials potentiating standard chemotherapy drugs' effect

    Science.gov (United States)

    Kazantsev, S. O.; Korovin, M. S.

    2017-09-01

    Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

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

    Science.gov (United States)

    Boudreault, Patrick; Palmer, Christina

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Aronsson, Mattias; Walfridsson, Håkan; Janzon, Magnus

    2014-01-01

    AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model......, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain......-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients. CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy...

  8. 75 FR 15440 - Guidance for Industry on Standards for Securing the Drug Supply Chain-Standardized Numerical...

    Science.gov (United States)

    2010-03-29

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Standards for Securing the Drug... announcing the availability of a guidance for industry entitled ``Standards for Securing the Drug Supply... issued under the Federal Food, Drug, and Cosmetic Act (the act), which requires FDA to develop standards...

  9. Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies

    Directory of Open Access Journals (Sweden)

    Ju Yup Lee

    2016-01-01

    Full Text Available A new treatment strategy is needed, as the efficacy of triple therapy containing clarithromycin—the current standard treatment for Helicobacter pylori infection—is declining. Increasing antibiotic resistance of H. pylori is the most significant factor contributing to eradication failure. Thus, selecting the most appropriate regimen depending on resistance is optimal, but identifying resistance to specific antibiotics is clinically challenging. In a region suspected to have high clarithromycin resistance, bismuth quadruple therapy and so-called nonbismuth quadruple therapies (sequential, concomitant, and sequential-concomitant hybrid are some first-line regimen options. However, more research is needed regarding appropriate second-line treatments after first-line treatment failure. Tailored therapy, which is based on antibiotic sensitivity testing, would be optimal but has several limitations for clinical use, and an alternative technique is required. A novel potassium-competitive acid blocker-based eradication regimen could be a valuable eradication option in the near future.

  10. Pharmacognostic standardization of Homoeopathic drug: Juniperus virginiana L.

    OpenAIRE

    P Padma Rao; P. Subramanian; P Sudhakar; P R Reddy

    2015-01-01

    Background: Juniperus virginiana L., commonly known as ′red cedar′ in English is a well-known evergreen tree belonging to the family Cupressaceae. The leaves and young aerial shoots are used for preparation of medicine in Homoeopathy. Objective: Standardization is the quintessential aspect which ensures purity and quality of drugs. Hence, the pharmacognostic and physico-chemical studies are carried out to facilitate the use of authentic and correct species of raw drug plant material with ...

  11. First-line treatment of advanced ALK-positive non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Gandhi S

    2015-09-01

    Full Text Available Shipra Gandhi,1 Hongbin Chen,2 Yujie Zhao,2 Grace K Dy2 1Department of Internal Medicine, State University of New York, 2Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA Abstract: Non-small-cell lung cancer (NSCLC is one of the leading causes of cancer deaths, both within the US and worldwide. There have been major treatment advances in NSCLC over the past decade with the discovery of molecular drivers of NSCLC, which has ushered in an era of personalized medicine. There are several actionable genetic aberrations in NSCLC, such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK. In 3%–7% of NSCLC, a chromosomal inversion event in chromosome 2 leads to fusion of a portion of the ALK gene with the echinoderm microtubule–associated protein-like 4 (EML4 gene. The constitutive activation of the ALK fusion oncogene renders it vulnerable to therapeutic intervention. This review focuses on the first-line treatment of advanced ALK-positive NSCLC using ALK inhibitors. Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC. However, acquired resistance inevitably develops. The central nervous system is a sanctuary site that represents a common site for disease progression as well. Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood–brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well. In this review, we provide summary of the clinical experience with these drugs in the treatment of ALK-positive NSCLC. Keywords: non-small-cell lung cancer, ALK, first line, crizotinib, pemetrexed

  12. [Indications for methotrexate in gynecology outside the first-line treatment of ectopic tubal pregnancies].

    Science.gov (United States)

    Misme, H; Agostini, A; Dubernard, G; Tourette, C

    2015-03-01

    The objective of this work is to discuss the indications for methotrexate in gynecology outside the first-line treatment of tubal ectopic pregnancy. In tubal ectopic pregnancy, the prophylactic use of systemic methotrexate can be discussed when performing laparoscopic salpingotomy. In case of failure of salpingotomy, administration seems justified especially if it avoids re-intervention. The combination of methotrexate with other therapies such as mifepristone, potassium chloride or gefitinib is not recommended in the treatment of ectopic pregnancy. For non-tubal ectopic pregnancy, the intramuscular or local administration of methotrexate is an acceptable treatment for uncomplicated interstitial pregnancies. For uncomplicated cervical or cesarean scar pregnancies, the local administration of methotrexate should be considered as a first-line treatment. For ovarian pregnancies, methotrexate should not be a first-line treatment, surgical treatment remains the standard. Asymptomatic women presenting with a pregnancy of unknown location and plateauing serum hCG concentration<2000 UI/L can be managed expectantly: it is recommended to take an additional quantitative hCG serum level after 48 hours. Thus, methotrexate is not recommended in the first intention. Other gynecological indications were discussed: methotrexate is not recommended in the management of first-trimester miscarriages or in the management of placenta accreta. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Pharmacognostic standardization of Homoeopathic drug: Juniperus virginiana L.

    Directory of Open Access Journals (Sweden)

    P Padma Rao

    2015-01-01

    Full Text Available Background: Juniperus virginiana L., commonly known as ′red cedar′ in English is a well-known evergreen tree belonging to the family Cupressaceae. The leaves and young aerial shoots are used for preparation of medicine in Homoeopathy. Objective: Standardization is the quintessential aspect which ensures purity and quality of drugs. Hence, the pharmacognostic and physico-chemical studies are carried out to facilitate the use of authentic and correct species of raw drug plant material with established parametric standards for manufacturing the drug. Materials and Methods: Pharmacognostic studies on leaves and young aerial parts of authentic samples of J. virginiana L. have been carried out; physico-chemical parameters of raw drug viz., extractive values, ash values, formulation, besides weight per mL, total solids, alcohol content along with High Performance Thin Layer Chromatography (HPTLC and ultraviolet visible studies have been worked out for mother tincture. Results: The leaves are needles, narrow and sharp at tips; stems are round with greyish white to brown bark possessing small lenticels and covered by imbricate leaves. Epidermal cells in the surface have polygonal linear sides with pitted walls containing crystals and starch. Stomata exclusively occur on the adaxial surface in linear rows. Hypodermis of leaf in T.S. is marked with 1-2 layered lignified sclerenchyma. 2-4 secretory canals are present with one conspicuously beneath midvein bundle. The young terminal axis is sheathed by two closely surrounding leaves while the mature stem possess four leaf bases attached. Vascular tissue of stem possesses predominant xylem surrounded by phloem containing sphaeraphides, prismatic crystals and starch grains. Uniseriate rays occur in the xylem. Mature stem possess shrivelled cork, followed by the cortex. Physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and

  14. Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.

    Science.gov (United States)

    Eriksen, J; Mwankusye, S; Mduma, S; Kitua, A; Swedberg, G; Tomson, G; Gustafsson, L L; Warsame, M

    2004-06-01

    A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine.

  15. Response to first line chemotherapy regimen is associated with efficacy of nivolumab in non-small-cell lung cancer.

    Science.gov (United States)

    Kaderbhai, Courèche-Guillaume; Richard, Corentin; Fumet, Jean David; Aarnink, Anne; Ortiz-Cuaran, Sandra; Pérol, Maurice; Foucher, Pascal; Coudert, Bruno; Favier, Laure; Lagrange, Aurélie; Limagne, Emeric; Boidot, Romain; Ladoire, Sylvain; Poudenx, Michel; Ilie, Marius; Hofman, Paul; Saintigny, Pierre; Ghiringhelli, François

    2017-01-01

    Nivolumab, an anti PD-1 checkpoint inhibitor has demonstrated efficacy in metastatic non-small-cell lung cancer (NSCLC) patients after failure to standard chemotherapy. Standard chemotherapy agents could promote antitumor immune response. We thus examined whether the response to first line chemotherapy could impact on nivolumab benefit. One hundred and 15 patients with NSCLC were included in this retrospective study from 4 different French centers. Forty-three squamous cell carcinomas (SCC), and 72 non-SCC received nivolumab between 2015 and 2016 (3 mg/kg IV Q2W). Response to first-line chemotherapy and to nivolumab was retrospectively assessed on CT-scan by central review. The association between RECIST response to first-line chemotherapy and nivolumab efficacy were determined using Fisher's exact test and Cox proportional hazard model. Respectively 46 (40%), 44 (38%) and 25 (22%) patients experienced partial response (PR), stable disease (SD), or progressive disease (PD) in response to first-line platinum- based chemotherapy. Twenty 5 (21%), 34 (30%), 56 (49%) respectively experienced PR, SD and PD in response to nivolumab. 60% (54/90) of patients who experienced clinical benefit (PR + SD) after first-line chemotherapy also had clinical benefit after nivolumab, while only 20% (5/25) of patients with initial PD subsequently experienced clinical benefit with nivolumab (Fisher's exact test, P = 0.001). The type of first-line doublet chemotherapy did not influence the response rate to nivolumab. Univariate and multivariate analyses showed that patients with clinical benefit from first-line chemotherapy had higher second-line PFS (P = 0.003) (median PFS on nivolumab of 5, 3.3 and 1.9 months for patients with PR, SD and PD in response to first-line therapy, respectively). Similar results were obtained for OS. Thus this study suggests that the efficacy of first-line chemotherapy may be a valuable surrogate marker of the benefit of nivolumab in terms of PFS and OS.

  16. Pharmacognostic and physicochemical standardization of homoeopathic drug: Rumex crispus L.

    Directory of Open Access Journals (Sweden)

    Subramanian Palani

    2016-01-01

    Full Text Available Background: Rumex crispus L., commonly called as "yellow dock" in English, "patience frisee" in French, and "Ampfer" in German, and ′aceda de culebra′ in Spanish is a well-known herb belonging to Polygonaceae. Roots of the herb are used as medicine in homoeopathy. Objective: The pharmacognostic and physicochemical studies on roots have been carried out to enable the use of correct species and standardize the raw material. Materials and Methods: Pharmacognostic studies on roots of authentic raw drug have been carried out; physicochemical parameters, namely, extractive value, ash values, formulation besides weight per mL, total solids, alcohol content along with high-performance thin layer chromatography (HPTLC and ultraviolet studies for mother tincture have been worked out. Results: Roots are blackish-brown, wiry, rounded with irregular striations, tortuous; internally, it is softwood, light-yellow, and fracture fibrous. Phellem is 8-10 layered, discontinuous, and tanniniferous. Phellogen is two-layered and contains inulin crystals in few. Outer phelloderm is 12-16 layered often containing spherocrystals and associated with stone cells. Secondary phloem is up to 25 layered. Xylem is in the form of strips. The physicochemical properties and HPTLC values of the drug are standardized and presented. Conclusion: The powder microscopic features and organoleptic characters along with anatomical and physicochemical studies are diagnostic to establish standards for the drug.

  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

    DEA clinical centres in five West-African countries. We estimated the incidence of switch (at least one a drug class change) within 24 months of ART and associated factors were identified in a multinomial logistic regression. Among children with clinical-immunological failure, we estimated the 24-month...... 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....... Of these children, 21 (7%) switched to second-line after a median time of 21 weeks in failure. This was associated with older age [subdistribution hazard ratio (sHR) 1.21, 95% confidence interval (95% CI) 1.10-1.33] and longer time on ART (sHR 1.16, 95% CI 1.07-1.25). CONCLUSION: Switches for clinical failure were...

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

    Directory of Open Access Journals (Sweden)

    Carmen Diana Schweighofer

    2010-03-01

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

  19. Comparison of gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer.

    Science.gov (United States)

    Park, Kwonoh; Kim, Kyu-Pyo; Park, Seongjoon; Chang, Heung-Moon

    2017-02-01

    It remains unclear whether capecitabine combined with cisplatin would show similar effects compared with standard therapy using gemcitabine and cisplatin in advanced biliary tract cancer (BTC). Patients with advanced BTC who were treated with first-line chemotherapy at Asan Medical Center were retrospectively analyzed. All patients received either cisplatin followed by gemcitabine on days 1 and 8 every 3 weeks (GP group), or capecitabine on days 1-14 with cisplatin on day 1 every 3 weeks (XP group). Of the 134 patients who met the inclusion criteria, 78 received XP and 56 were treated with GP. After a median follow-up of 26.2 months, the progression-free survival was 5.7 months for XP versus 4.1 months for GP (hazard ratio [HR] = 0.81, P = 0.31). The overall survival (OS) was 11.0 months for XP versus 9.8 months for GP (HR = 0.84, P = 0.36). In the multivariate analysis, there were no significant differences in PFS and OS between the two groups. XP seems to be as effective as GP in patients with advanced BTC. The XP regimen is feasible and might offer increased convenience regarding the schedule of drug administration. © 2016 John Wiley & Sons Australia, Ltd.

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

    Science.gov (United States)

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

    2014-04-21

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

  1. High efficacy of first-line ART in a West African cohort, assessed by dried blood spot virological and pharmacological measurements.

    Science.gov (United States)

    de Truchis, Pierre; Lê, Minh Patrick; Daou, Mamane; Madougou, Boubacar; Nouhou, Yacouba; Moussa Saley, Sahada; Sani, Achirou; Adehossi, Eric; Rouveix, Elisabeth; Saidou, Mamadou; Peytavin, Gilles; Delaugerre, Constance

    2016-11-01

    The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification 100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented. Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3; 81% had VL ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infected patients in low-income countries. © 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.

  2. 75 FR 70011 - Guidance for Industry, Mammography Quality Standards Act Inspectors, and Food and Drug...

    Science.gov (United States)

    2010-11-16

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry, Mammography Quality Standards Act Inspectors, and Food and Drug Administration Staff; The Mammography Quality Standards Act Final Regulations.... Quality control testing of computer controlled compression devices; 12. Mammography equipment evaluations...

  3. 21 CFR 70.10 - Color additives in standardized foods and new drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Color additives in standardized foods and new drugs. 70.10 Section 70.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVES General Provisions § 70.10 Color additives in standardized foods and new...

  4. 78 FR 42084 - Electronic Study Data Submission; Data Standard Support; Availability of the Center for Drug...

    Science.gov (United States)

    2013-07-15

    ... HUMAN SERVICES Food and Drug Administration Electronic Study Data Submission; Data Standard Support... Drug Administration, HHS. ACTION: Notice. SUMMARY: The Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA) is announcing the availability of the CDER Data Standards...

  5. First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma.

    Science.gov (United States)

    Fujimoto, Eriko; Kijima, Takashi; Kuribayashi, Kozo; Negi, Yoshiki; Kanemura, Shingo; Mikami, Koji; Doi, Hiroshi; Kitajima, Kazuhiro; Nakano, Takashi

    2017-09-01

    Mesothelioma of peritoneal origin has wider variation in treatment outcomes than mesothelioma of pleural origin, likely because peritoneal mesothelioma comprises borderline malignant variants and aggressive malignant peritoneal mesothelioma (MPeM). This study retrospectively evaluates the efficacy of first-line systemic pemetrexed and cisplatin chemotherapy in MPeM. Twenty-four patients with histologically proven MPeM were treated with pemetrexed plus cisplatin as a first-line systemic chemotherapy. The response was evaluated radiologically according to standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Twenty-two patients underwent 18 F-fluorodeoxyglucose positron emission tomography/(FDG-PET)/computed tomography(CT) at baseline, and 13 were eligible for metabolic assessment. Two complete responses and 9 partial responses were achieved. Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively. Wet- type MPeM had significantly longer survival (40.9 months median) than other clinical types (15.5 months) (P = 0.045). The baseline maximum standardized uptake value in 22 patients was 8.93 (range, 2.5-16.77). Systemic pemetrexed plus cisplatin is active for MPeM. Disparity with the outcome of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) needs to receive more emphasis, since peritoneal mesothelioma has a 5-year survival rate of 50%.

  6. Use of Low Dose Ziconotide as First-Line Intrathecal Monotherapy.

    Science.gov (United States)

    Prusik, Julia; Argoff, Charles; Peng, Sophia; Pilitsis, Julie G

    2017-06-01

    Ziconotide use in intrathecal drug therapy (IDT) has been limited by dosing related side effects. We examine our experience with ziconotide as a first line IDT monotherapy in patients with chronic pain and present our low and slow dosing algorithm aimed at reducing these patient experienced side effects while adequately managing pain. We retrospectively reviewed demographics, dosing, and outcomes of 15 consecutive patients with complete three-month data sets implanted with intrathecal pain pumps more than three years utilizing ziconotide as a first-line monotherapy. Ziconotide response was assessed at visit 5 (69 ± 10 days) and responders were characterized by having 30% or greater improvement in numerical rating scale scores (n = 7), or activities of daily living (ADL) (n = 7). Eight of our patients had a response in at least one measure (53%). In our eight responders, NRS score decreased from 8.4 ± 0.7 at baseline (consult visit) to 2.4 ± 1.0 at 2.6 months and 4.0 ± 1.3 at most recent follow-up, mean of 12.9 months after implant. We noted that our responders tended to have neuropathic pain with an objective etiology. Initial dosing in 12 patients was 1.2 mcg/day (range for the other three patients was 0.6-1.4). Following initial dosing, visits were at 2-4 week intervals with mean titration doses between 1.1 and 2.8 mcg/day. Slight dizziness in two patients and transient urinary retention in one patient occurred, all resolving with dose reduction. No patients had discontinued use at three-month follow-up. We present our experience with low and slow ziconotide IDT as a first-line monotherapy, which showed no side effects resulting in discontinuation of the medication at three-month follow-up. Using a conservative dosing strategy, we were able to effectively treat 53% of patients. © 2016 International Neuromodulation Society.

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

    Science.gov (United States)

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

    2017-09-01

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

  8. Should radioiodine be the first-line treatment for paediatric Graves' disease?

    Science.gov (United States)

    West, James D; Cheetham, Timothy D; Dane, Carole; Natarajan, Anuja

    2015-07-01

    Debate exists regarding the optimal treatment strategy for paediatric Graves' disease with radioiodine (RAI), and surgery, usually reserved for failure of medical therapy. We present our own experience to introduce a review of the published literature focussing on the predictors of remission after antithyroid drug (ATD) therapy from diagnosis, and discuss whether RAI should be considered as a first-line therapy. A retrospective analysis of all diagnosed cases of paediatric Graves' disease presenting to a large District General Hospital. Thirteen patients were diagnosed with Graves' disease between February 2004 and May 2013. The median age at diagnosis was 13.7 years (range 7.2-17.1 years) with a female:male ratio of 11:2. Some nine patients completed a 2-year course of carbimazole out of which 8 relapsed after a mean duration of 0.82 years (range 0.08-1.42 years); the ninth currently remains in remission. Of the eight patients who relapsed, three have undergone RAI treatment. Two patients failed to tolerate carbimazole treatment, one of whom received RAI treatment because surgery was contraindicated and one patient with severe autism proceeded to RAI treatment due to poor compliance and persistent hyperthyroidism. Prognostic factors at presentation predicting a low likelihood of remission following ATD treatment include younger age, non-Caucasian ethnicity, and severe clinical and/or biochemical markers of hyperthyroidism. Psycho-social factors including compliance also influence management decisions. In specifically selected patients presenting with paediatric Graves' disease, the benefits and risks of radioactive iodine as a potential first-line therapy should be communicated allowing families to make informed decisions.

  9. First-line Nurse Managers' Preconditions for Practise : The Important Interplay between Person and Organization

    OpenAIRE

    Skytt, Bernice

    2007-01-01

    The aim was to study personal and organizational conditions for first-line nurse managers and to identify and assess the skills and abilities important for leadership and management. Interviews were conducted with 5 first-line nurse managers, 5 registered nurses, 5 assistant nurses and one head of department delineating their perceptions of current and ideal roles of first-line nurse managers. Factor analysis was conducted to estimate validity and reliability of the Leadership and Management ...

  10. Delayed pressure urticaria - dapsone heading for first-line therapy?

    Science.gov (United States)

    Grundmann, Sonja Alexandra; Kiefer, Sabine; Luger, Thomas Anton; Brehler, Randolf

    2011-11-01

    Pressure urticaria as a subform of physical urticaria is rare and treatment is often difficult. Established therapeutic regimes include antihistamines (generally exceeding approved dosages in order to achieve a therapeutic benefit) or antihistamines combined with montelukast. Complete relief of symptoms is difficult. We used dapsone as an early therapeutic alternative in the event of treatment failure and established a standardized therapeutic regime at our clinic. We surveyed 31 patients retrospectively who had received dapsone between 2003-2009. In 74 % of patients in whom symptoms persisted despite established therapies, the results of treatment with dapsone were good or very good. Longer-term pressure urticaria and the co-existence of a chronic spontaneous urticaria were associated with a smaller benefit (pdapsone in patients with pressure urticaria has such a good risk-benefit ratio that we support early treatment initiation. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

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

    Science.gov (United States)

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

    2014-11-01

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

  12. 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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevaci......The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined...

  14. Intratympanic Methylprednisolone Injection as First Line Therapy for Idiopathic Sudden Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Mukul Patar

    2017-08-01

    Full Text Available Introduction Steroid therapy is considered to be the gold standard for sudden sensorineural hearing loss (SSNHL. Delivering steroids by intratympanic injection is more efficient than systemic injections with minimum or no side effects. The present study was aimed to evaluate the efficacy and safety of intratympanic methylprednisolone injections as initial first line therapy for unilateral idiopathic SSNHL and the ease of giving it by otoendoscopy. Materials and Methods A prospective analysis was performed for the patients diagnosed as unilateral idiopathic SSNHL from April 2014 to April 2016 and receiving intratympanic steroids injections as first line therapy. Patients with unilateral sensorineural hearing loss of at least 30 dB at 3 contiguous frequencies occurring within a period of not more than 3 days are only included. All of the intratympanic steroid (ITS injections were administered as OPD procedures. Each patient was treated by 3 injections given at 3 days interval.  Results A total of 22 patients who underwent primary intratympanic steroid (ITS injection for unilateral SSNHL during the study period were included in the study. The mean age was 42.22 years (+ 9.79 and age ranged from 27 to 68 years. Patients included in our study came within 2nd to 27th day of occurrence of deafness and the mean duration (days from onset of disease to start of ITS was 7.86 days. The average hearing gain in our study was 44.22 dB. In the present study 11 patients (50% showed complete hearing improvement and 10 cases (45.45% had partial and one (4.54% showed no hearing recovery at 3 weeks follow up period. Conclusion Minimal systemic absorption with minimum or no systemic effects and high percentage of success rate encouraged the surgeons to prefer ITS as primary therapy for idiopathic unilateral SSNHL. It is effective, cheap, well-tolerated and can be performed as OPD procedure.

  15. 75 FR 34452 - Center for Drug Evaluation and Research Data Standards Plan; Availability for Comment

    Science.gov (United States)

    2010-06-17

    ... HUMAN SERVICES Food and Drug Administration Center for Drug Evaluation and Research Data Standards Plan... development of a comprehensive data standards program in the Center for Drug Evaluation and Research (CDER... Administration (FDA) is announcing the availability for public comment of the draft document entitled ``CDER Data...

  16. Concurrent Specialized Palliative Care Upon Initiation of First-Line Chemotherapy for Cancer Progression: Is It Early Enough?

    Science.gov (United States)

    Nakajima, Nobuhisa; Abe, Yasushi

    2016-05-01

    To evaluate the effectiveness of specialized palliative care (PC) administered at the time of administration of first-line chemotherapy for cancer progression. Patients who received regular specialist PC concomitantly with first-line chemotherapy after being diagnosed with progressive disease assigned to PC group. Patients transferred to palliative care unit (PCU) after discontinuation of chemotherapy were assigned to standard care (SC) group. We evaluated quality of palliative care using Support Team Assessment Schedule, quality of life (QOL) using Good Death Inventory, and short-term mortality in PCU. A total of 28 and 63 patients patients were assigned to PC and SC groups, respectively. Physical symptoms, anxiety, communication scores, and QOL scores were significantly higher in the PC group (P < .001). Short-term mortality (<14 days) was significantly higher in the SC group (P = .0005). This approach may facilitate high quality of PC. © The Author(s) 2014.

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  18. Chemometrics: A new scenario in herbal drug standardization

    Directory of Open Access Journals (Sweden)

    Ankit Bansal

    2014-08-01

    Full Text Available Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency. Key words: Chemometrics, HELP, Herbal drugs, PCA, OPA

  19. [A study of leadership training program demands of first-line nurse managers in university hospitals].

    Science.gov (United States)

    Koh, M S

    1998-01-01

    There is an important concern regarding the First-line nurse manager's leadership because of the recognition that effectiveness of Leadership in this position results in benefits for the whole health care organization. So knowledge and practice of effective leadership behavior are now more essential to nursing than ever before. First-line Nurse Managers must be effective leaders to meet today's challenge because staff nurse, patient are affected by them. So the purpose of this study was to identify and to analyse the need for Leadership program of First Line nurse managers in university hospitals. There were three major purposes of this study. First, identify First-line nurse managers general characteristic, second, identify their experience of leadership training, third, identify and analysis their demands for leadership training program. The subjects for this study was 167 First-line nurse manager randomly from 18 university hospitals in Korea. The data were collected through questionnaires from Oct. 13th to Nov. 20th, 1997, data was analysed using frequencies and percentages. Especially the steps of analysis of descriptions were as follows: Initial analysis centered on the identification of the demands of first-line nurse managers. Later analysis collapsed the demands into broad categories. From the collect data, 283 demands of first-line nurse managers were identified. These demands were then sorted into 3 broad categories that included: Self development as first-line nurse managers, relationship with others, and practice The result of the study were as follows: 1) Most of nurse managers (79.6%) had leadership training course and had good experience to improve self leadership. 2) Their demands of leadership training course are as follows: First, for self as first-line nurse managers, they want to learn leadership theory, identify their leadership style and then develop their leadership skill. Second, for others as first-line nurse managers, they want to improve

  20. Neutropenia-related costs in patients treated with first-line chemotherapy for advanced non-small cell lung cancer.

    Science.gov (United States)

    Stokes, Michael E; Muehlenbein, Catherine E; Marciniak, Martin D; Faries, Douglas E; Motabar, Saeed; Gillespie, Theresa W; Lipscomb, Joseph; Knopf, Kevin B; Buesching, Don P

    2009-10-01

    agent. Costs were summed for 2 main types of cost measures: neutropenia-related costs, defined as costs for claims with either a primary or secondary diagnosis of neutropenia, and costs unrelated to neutropenia. Costs were classified using ICD-9-CM diagnosis and procedure codes appearing on the claims, with confidence intervals [CIs] for cost measures estimated by using nonparametric bootstrapping methods. Group comparisons of patient characteristics, medical utilization, and cost study measures were made using 2-sided Pearson chi-square and t-test statistics for categorical and continuous measures, respectively. The no neutropenia group was used as the reference category for comparisons involving patient characteristic, medical utilization, and total all-cause health care cost study measures. For total neutropenia-related costs, afebrile and febrile neutropenia study groups were compared. Among elderly patients treated first-line for advanced NSCLC, 5,138 met inclusion criteria, of whom 1,228 (23.9%) developed afebrile (n = 740, 14.4%) or febrile neutropenia (n = 488, 9.5%) while on first-line chemotherapy. Mean per patient costs for treating neutropenia during first-line chemotherapy were $12,148 (standard deviation [SD] = $15,432, 95% confidence interval [CI] = $10,915-$13,607) for patients with febrile neutropenia and $3,099 (SD = $4,541, 95% CI = $2,796-$3,431) for patients with afebrile neutropenia (Pchemotherapy) of 4.5 (4.8) and 5.5 (7.0) months, respectively. Expressed as a percentage of total all-cause health care costs during first-line chemotherapy, neutropenia-related costs accounted for 32.2% of total costs for patients with febrile neutropenia (mean [SD] = $37,694 [$26,078]) and 9.1% of total costs for patients with afebrile neutropenia (mean [SD] = $34,204 [$26,317]). Mean neutropenia-related costs per patient per month (PPPM) during first-line chemotherapy were $2,700 for patients with febrile neutropenia and $563 for patients with afebrile neutropenia

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

    Science.gov (United States)

    Peng, Xiao; Liu, Yilan; Zeng, Qingsong

    2015-12-01

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

  2. Non-cross resistant sequential single agent chemotherapy in first-line advanced non-small cell lung cancer patients: Results of a phase II study

    NARCIS (Netherlands)

    V. Surmont; J.G.J.V. Aerts (Joachim); K.Y. Tan; F.M.N.H. Schramel (Franz); R. Vernhout (Rene); H.C. Hoogsteden (Henk); R.J. van Klaveren (Rob)

    2009-01-01

    textabstractBackground. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Orietta Zaniolo

    2013-06-01

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

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

    African Journals Online (AJOL)

    test to compare continuous and categorical data where appropriate. Since the survey obtained information that is part of routine ART practice and data were collected in an anonymized fashion, we did not obtain informed consent from patients.

  6. Breast enlargement in Malawian males on the standard first-line ...

    African Journals Online (AJOL)

    induced breast enlargement. Testosterone deficiency can occur in HIV infection. Causes of excess oestrogen include β-hCG-producing ... P450 2B6 and other liver enzymes involved in the metabolism of efavirenz, are well-documented in African ...

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

    Science.gov (United States)

    Acorn, S; Crawford, M

    1996-01-01

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

  8. Elderly onset rheumatoid arthritis: differential diagnosis and choice of first-line and subsequent therapy.

    Science.gov (United States)

    Villa-Blanco, Juan Ignacio; Calvo-Alén, Jaime

    2009-01-01

    Elderly onset rheumatoid arthritis (EORA) has been considered a benign form of rheumatoid arthritis (RA). However, it most probably encompasses different subsets of patients with distinct outcomes. According to data reported in the most recent studies directly comparing older and younger RA patients, it seems that, overall, the prognosis of EORA patients is not very different from that of other patients with this disease. However, some cases with negative rheumatoid factor and polymyalgia-like symptoms appear to be a distinct subset with a different genetic basis and a more benign course. The differential diagnosis of EORA from other rheumatological disorders that are prevalent in this stratum of the population, such as polymyalgia rheumatica, crystal-induced arthritis or osteoarthritis, may be complicated because these disorders can present with signs and symptoms similar to those of RA in some circumstances. A prompt diagnosis of true RA is important because early treatment should be implemented. It is recommended that therapy of EORA be tailored according to disease activity, with the aim of achieving clinical remission or the lowest possible level of disease activity in order to minimize potential functional sequelae. Co-morbidities and drug toxicity profiles are major considerations when choosing the most suitable therapy for EORA patients. Prudent use and careful follow-up of all treatments are also required because of the increased risk of adverse events in elderly patients. However, no special contraindications to the use of disease-modifying antirheumatic drugs in this age group apply, and use of biological therapies currently used in younger RA patients has also been described in these patients. Therefore, a therapeutic strategy for first-line and subsequent treatment that is in accordance with the disease activity of patients with EORA is suggested.

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

    Science.gov (United States)

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

    2017-07-01

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

  10. High dose amoxicillin-based first line regimen is equivalent to sequential therapy in the eradication of H. pylori infection.

    Science.gov (United States)

    Franceschi, F; Ojetti, V; Gabrielli, M; Petruzziello, C; Tortora, A; Gasbarrini, G; Lopetuso, L R; Scaldaferri, F; Gasbarrini, A

    2016-01-01

    Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin-resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy. We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed. Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (pamoxicillin based eradicating treatment is superior to standard triple therapy and equivalent to sequential therapy; compared to the latter, the shorter duration may represent an advantage.

  11. Vacuum-assisted closure for sternal wounds: a first-line therapeutic management approach.

    Science.gov (United States)

    Agarwal, Jayant P; Ogilvie, Michael; Wu, Liza C; Lohman, Robert F; Gottlieb, Lawrence J; Franczyk, Mietka; Song, David H

    2005-09-15

    . The authors report the largest series of patients treated with this therapy for post-sternotomy sternal wounds and believe it is safe and effective as a first-line therapy in the management of sternal wounds. The mortality rate from their study represents the patients' underlying disease process and comorbidities and is not a reflection of complications associated with the therapy. Vacuum-assisted closure therapy has been shown to decrease wound edema, decrease the time to definitive closure, and reduce wound bacterial colony counts. The authors have implemented the therapy for most patients with sternal wounds/mediastinitis at their institution, and believe it should be a standard protocol in the first-line management of these types of wounds.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    intervention (II), aimed to improve the adherence to recommendations on first-line antibiotics in patients with respiratory tract infections (RTIs). Methods: General practitioners (GPs) from different regions of Spain were offered two different interventions on antibiotic prescribing. They registered all.......8-26%), respectively. Conclusion: Multifaceted interventions targeting GPs can improve adherence to recommendations for first-line antibiotic prescribing in patients with RTI, with intensive interventions that include point-of-care testing being more effective....

  14. [Dimethyl fumarate (tecfidera) is the first line treatment choice in patients with remitting multiple sclerosis].

    Science.gov (United States)

    Shmidt, T E

    2017-01-01

    Dimethyl fumarate (DMF) is a new oral option for disease-modifying therapy (DMT) in patients with remitting multiple sclerosis as a first line treatment. The results of international randomized studies comparing DMF with placebo and other DMTs are presented. DMF is a DMT with promised efficacy and favorable safety profile that could be a treatment option for patients with suboptimal response for other first line DMTs and used as initial therapy for treatment-naive patients with unfavorable prognostic factors.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    The aim of this study was to investigate first-line nursing home managers’ views on their leadership and related to that, palliative care. Previous research reveals insufficient palliation, and a number of barriers towards implementation of palliative care in nursing homes. Among those barriers are issues related to leadership quality. First-line managers play a pivotal role, as they influence working conditions and quality of care. Nine first-line managers, from different nursing homes in Sweden participated in the study. Semi-structured interviews were conducted and analysed using qualitative descriptive content analysis. In the results, two categories were identified: embracing the role of leader and being a victim of circumstances, illuminating how the first-line managers handle expectations and challenges linked to the leadership role and responsibility for palliative care. The results reveal views corresponding to committed leaders, acting upon demands and expectations, but also to leaders appearing to have resigned from the leadership role, and who express powerlessness with little possibility to influence care. The first line managers reported their own limited knowledge about palliative care to limit their possibilities of taking full leadership responsibility for implementing palliative care principles in their nursing homes. The study stresses that for the provision of high quality palliative care in nursing homes, first-line managers need to be knowledgeable about palliative care, and they need supportive organizations with clear expectations and goals about palliative care. Future action and learning oriented research projects for the implementation of palliative care principles, in which first line managers actively participate, are suggested. PMID:25628769

  18. Long-term efficacy of first line antiretroviral therapy in Indian HIV-1 infected patients: a longitudinal cohort study.

    Directory of Open Access Journals (Sweden)

    Ujjwal Neogi

    Full Text Available Short term efficacy of combination antiretroviral therapy (cART in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings.A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression 2000 copies/mL. Adherence and treatment interruptions (>48 h were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs. Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations.Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines.

  19. Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.

    Science.gov (United States)

    Prithviraj, G K; Baksh, K; Fulp, W; Meredith, K; Hoffe, S; Shridhar, R; Almhanna, K

    2015-01-01

    Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we retrospectively present our single center experience. Between 1998 and 2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly area under the curve 5 and paclitaxel predominantly 175 mg/m(2)) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from diagnosis to death or last follow up, and progression-free survival was defined at time from cycle 1 to, progression or last follow up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Of the 134 patients evaluated, the median age at diagnosis was 65 years. Disease control rate was 62.6% (complete response: 11%, partial response: 28%, stable disease: 33%). Median overall survival from date of initial diagnosis was 15.5 months (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 5.3 months (95% CI 0.34-0.5). Grade III or greater toxicity occurred in 26.1% of patients. The most common grade III toxicities were neutropenia and neuropathy, present in 14.2% and 3.7% of the total study population, respectively. In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population. © 2014 International Society for Diseases of the Esophagus.

  20. Laparoscopic sleeve gastrectomy as first-line surgical treatment for morbid obesity among adolescents.

    Science.gov (United States)

    Ejaz, Aslam; Patel, Pankti; Gonzalez-Heredia, Raquel; Holterman, Mark; Elli, Enrique F; Kanard, Robert

    2017-04-01

    The increasing prevalence of obesity has necessitated the increasing use of bariatric surgery in the adolescent population. Outcomes following laparoscopic sleeve gastrectomy (LSG) among adolescents, however, have not been well-studied. We report outcomes following LSG as a first-line surgical therapy in patients under 21years of age. All patients who underwent LSG as a primary surgical option for morbid obesity were identified at the University of Illinois at Chicago between 2006 and 2014. Standard clinicopathologic and outcomes data were recorded. We identified 18 patients (13 females, 5 males) who underwent LSG. Mean patient age was 17.8±1.7years. Mean BMI among all patients was 48.6±7.2kg/m2 and did not differ by gender (P=0.68). One patient (5.6%) experienced a 30-day perioperative complication (pulmonary embolism). Median LOS following LSG was 3days (IQR: 2, 3). 2 patients (11.1%) were readmitted within 30-days because of feeding intolerance that resolved without invasive intervention. At a median follow-up of 10.6 (range: 0-38) months, percent excess weight loss (%EWL) among all patients was 35.6%. Among patients with at least 2years follow-up (n=3), %EWL was 50.2%. Laparoscopic sleeve gastrectomy in morbidly obese adolescents is a safe and feasible option. Short- and long-term weight loss appears to be successful following LSG. As such, LSG should be strongly considered as a primary surgical treatment option for all morbidly obese adolescents. Level IV. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shernan G Holtan

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

  2. Risk factors for the development of non-response to first-line treatment for tuberculosis in southern Vietnam.

    Science.gov (United States)

    Keane, V P; de Klerk, N; Krieng, T; Hammond, G; Musk, A W

    1997-10-01

    Acquired resistance to standard chemotherapy for tuberculosis (TB) is an increasing problem worldwide. Vietnam has one of the highest incidences of TB and also has a large population of potential migrants to other countries. Since 1979 the International Organisation for Migration (IOM) has been running a supervised programme of TB treatment for intending migrants from Vietnam where few facilities for bacteriological culture and sensitivity testing exist. This study aimed to assess the most important factors for predicting non-response to first-line treatment as treatment starts and whether any further indicators occur during the course of treatment which may enable more accurate prediction of non-response. In all, 130 subjects failing to respond to first-line therapy (cases) between 1990 and 1995 were compared with 673 subjects who responded to therapy (controls) on various demographic and clinical characteristics using logistic regression to create a prognostic index. Variables analysed included the patient history of past TB treatment, weight, age, sex and radiological and bacteriological findings. All subjects also tested negative for HIV status. The chief markers of successful response were x-ray signs and degree of sputum smear positivity. These markers provided a prognostic index with an optimal cutoff providing about 70% sensitivity and 80% specificity. Incorporating further measures obtained through the first 3 months of treatment improved the sensitivity to 80%. While this study enabled prediction of the majority of subjects failing to respond to first-line therapy, other factors need to be assessed before recommendations for altering treatment regimens can be made. The prognostic index could be useful in assessing subjects for closer supervision.

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

    Science.gov (United States)

    Rohr, Julia K; Ive, Prudence; Horsburgh, C Robert; Berhanu, Rebecca; Shearer, Kate; Maskew, Mhairi; Long, Lawrence; Sanne, Ian; Bassett, Jean; Ebrahim, Osman; Fox, Matthew P

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

  4. Pharmacognostic and physicochemical standardization of homoeopathic drug: Rumex crispus L.

    OpenAIRE

    Subramanian Palani; Padma Rao Pogaku; Sudhakar Penthala; P. S. Narayana

    2016-01-01

    Background: Rumex crispus L., commonly called as "yellow dock" in English, "patience frisee" in French, and "Ampfer" in German, and ′aceda de culebra′ in Spanish is a well-known herb belonging to Polygonaceae. Roots of the herb are used as medicine in homoeopathy. Objective: The pharmacognostic and physicochemical studies on roots have been carried out to enable the use of correct species and standardize the raw material. Materials and Methods: Pharmacognostic studies on roots of auth...

  5. Checklist for standardized reporting of drug-drug interaction management guidelines

    NARCIS (Netherlands)

    Floor-Schreudering, A.; Geerts, A.F.; Aronson, J.K.; Bouvy, M.L.; Ferner, R.E.; Smet, P.A.G.M. de

    2014-01-01

    PURPOSE: Inconsistencies and omissions in drug-drug interaction (DDI) management guidelines may lead to harm and suboptimal therapy. The purpose of this study was to define a checklist for DDI management guidelines to help developers produce high-quality guidelines that will support healthcare

  6. Male first-line managers' experiences of the work situation in elderly care: an empowerment perspective.

    Science.gov (United States)

    Hagerman, Heidi; Engström, Maria; Häggström, Elisabeth; Wadensten, Barbro; Skytt, Bernice

    2015-09-01

    To describe male first-line managers' experiences of their work situation in elderly care. First-line managers' work is challenging. However, less attention has been paid to male managers' work situation in health care. Knowledge is needed to empower male managers. Fourteen male first-line managers were interviewed. The interview text was subjected to qualitative content analysis. Work situations were described as complex and challenging; challenges were the driving force. They talked about 'Being on one's own but not feeling left alone', 'Having freedom within set boundaries', 'Feeling a sense of satisfaction and stimulation', 'Feeling a sense of frustration' and 'Having a feeling of dejection and resignation'. Although the male managers report deficiencies in the support structure, they largely experience their work as a positive challenge. To meet increasing challenges, male first-line managers need better access to supportive structural conditions. Better access to resources is needed in particular, allowing managers to be more visible for staff and to work with development and quality issues instead of administrative tasks. Regarding organisational changes and the scrutiny of management and the media, they lack and thus need support and information from superiors. © 2013 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2017-11-16

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

  8. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Carbone, D. P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M. M.; Ciuleanu, T. -E.; Badin, F.; Ready, N.; Hiltermann, T. J. N.; Nair, S; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J. M.; Rodriguez-Abreu, D.; Borghaei, H.; Blumenschein, G. R.; Villaruz, L. C.; Havel, L.; Krejci, J.; Corral Jaime, J.; Chang, C. -H.; Geese, W. J.; Bhagavatheeswaran, P.; Chen, Alexander C.; Socinski, M. A.

    2017-01-01

    BACKGROUND Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  9. A decade of Anti-Retroviral Therapy in Nigeria: Efficacy of First Line ...

    African Journals Online (AJOL)

    Alasia Datonye

    treatment-naive patients following widespread use of ART after a significant period of time. In this study, we evaluated the efficacy of the commonly used first line ARVs in treatment-naive HIV infected patients following widespread use of ARVs. Our primary measures were body mass index (BMI), CD4+ cell counts and viral ...

  10. Comparing the Efficacy of Concomitant Therapy with Sequential Therapy as the First-Line Therapy of Helicobacter pylori Eradication

    Directory of Open Access Journals (Sweden)

    Sung Min Jung

    2016-01-01

    Full Text Available Background. The decline of Helicobacter pylori (H. pylori eradication rates with standard triple therapy resulted in a search for novel therapies for first-line therapy of H. pylori infection. Aim. The aim of the study is to compare the efficacy of concomitant therapy with sequential therapy as the first-line therapy of H. pylori eradication. Methods. We reviewed medical records of patients who were confirmed to have H. pylori infection and received eradication treatment from September 2012 to March 2015. The concomitant group was treated with rabeprazole, amoxicillin, clarithromycin, and metronidazole for 7 days. The sequential group was treated with rabeprazole and amoxicillin for 5 days and then rabeprazole, clarithromycin, and metronidazole for an additional 5 days. Six weeks after the treatment period, patients in both groups underwent 13C-Urea breath test (UBT to confirm H. pylori eradication. Results. The eradication rate was 90.3% in the concomitant group and 85.5% in the sequential group. However, the eradication rates between the two groups showed no statistical difference (P=0.343. Conclusion. No statistical difference was found in eradication rates between the two groups. However, in areas where antibiotic resistance is high, concomitant therapy may be more effective than sequential therapy for H. pylori eradication.

  11. 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

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

    Science.gov (United States)

    Rodela, E S

    1991-04-01

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

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

    Science.gov (United States)

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

    2017-10-24

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

  14. The management of first-line biologic therapy failures in rheumatoid arthritis: Current practice and future perspectives.

    Science.gov (United States)

    Favalli, Ennio Giulio; Raimondo, Maria Gabriella; Becciolini, Andrea; Crotti, Chiara; Biggioggero, Martina; Caporali, Roberto

    2017-10-14

    The introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs) has dramatically changed the management of rheumatoid arthritis (RA). However, in a real-life setting about 30-40% of bDMARD treated patients experience drug discontinuation because of either inefficacy or adverse events. According to international recommendations, to date the best strategy for managing first-line bDMARD failures has not been defined yet and available data (especially on TNF inhibitors [TNFis]) seem to drive toward a personalized approach for the individual patient. Some TNFi partial responders may benefit from optimization of concomitant methotrexate therapy or from switching to a different concomitant sDMARD such as leflunomide. Conversely, apart from infliximab, TNFi dose escalation seems to be poor efficacious and poor cost-effective compared with alternative strategies. Albeit counterintuitive, the use of a second TNFi after the failure of the first-one (cycling strategy) is supported by clear evidences and has become widespread in the 2000s as the result of the limited alternative options till the introduction of bDMARDs with a mechanism of action other than TNF blockade. Nowadays, the use of abatacept, rituximab, tocilizumab, or JAK inhibitors as second-line agent (swapping strategy) is strongly supported by RCTs and real-life experiences. In the absence of head-to-head trials directly comparing these two strategies, meta-analyses of separated RCTs failed to find significant differences in favor of one or another choice. However, results from most observational studies, including well designed prospective pragmatic randomised analyses, demonstrated the superiority of swapping over cycling approach, whereas only few studies reported a comparable effectiveness. In this review, we aimed to critically analyze all the potential therapeutic options for the treatment of first-line bDMARD failures in order to provide a comprehensive overview of available strategies to be

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    -analysis. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients with an objective response, and toxicity. Statistical analyses were by intention-to-treat, stratified by trial. Overall survival and progression-free survival were compared by log-rank test......BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare....... The proportion of patients with an objective response was compared with a Mantel-Haenszel test. Prespecified analyses explored effect variations by trial and patient characteristics. FINDINGS: Five eligible trials were identified; individual patient data could be collected from four of these trials, which...

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

    Directory of Open Access Journals (Sweden)

    Soo-Yon Rhee

    2017-04-01

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

  17. Clinical Impact of the Number of Treatment Cycles in First-Line Docetaxel for Patients With Metastatic Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

    BACKGROUND: We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. PATIENTS AND METHODS: Charts from 421 consecutive patients who initiated standard treatment with doc......BACKGROUND: We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. PATIENTS AND METHODS: Charts from 421 consecutive patients who initiated standard treatment......, respectively). Reasons for treatment discontinuation and postdocetaxel treatments were registered. Prostate-specific antigen (PSA) responses were defined as a confirmed ≥ 50% decrease in baseline PSA levels. Overall survival (OS) was calculated from start of therapy using the Kaplan-Meier method. Cox...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    Science.gov (United States)

    Isosaari, Ulla

    2011-01-01

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

  20. Systematic review: What is the best first-line approach for cesarean section ectopic pregnancy?

    Directory of Open Access Journals (Sweden)

    Mine Kanat-Pektas

    2016-04-01

    Hysteroscopy and laparoscopic hysterotomy are safe and efficient surgical procedures that can be adopted as primary treatment modalities for CSEP. Uterine artery embolization should be reserved for cases with significant bleeding and/or a high suspicion index for arteriovenous malformation. Systemic methotrexate and D&C are not recommended as first-line approaches for CSEP, as these procedures are associated with high complication and hysterectomy rates.

  1. [Benzodiazepines should still be first-line treatment for alcohol withdrawal].

    Science.gov (United States)

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

    2017-01-16

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

  2. Systematic derivation of an Australian standard for Tall Man lettering to distinguish similar drug names.

    Science.gov (United States)

    Emmerton, Lynne; Rizk, Mariam F S; Bedford, Graham; Lalor, Daniel

    2015-02-01

    Confusion between similar drug names can cause harmful medication errors. Similar drug names can be visually differentiated using a typographical technique known as Tall Man lettering. While international conventions exist to derive Tall Man representation for drug names, there has been no national standard developed in Australia. This paper describes the derivation of a risk-based, standardized approach for use of Tall Man lettering in Australia, and known as National Tall Man Lettering. A three-stage approach was applied. An Australian list of similar drug names was systematically compiled from the literature and clinical error reports. Secondly, drug name pairs were prioritized using a risk matrix based on the likelihood of name confusion (a four-component score) vs. consensus ratings of the potential severity of the confusion by 31 expert reviewers. The mid-type Tall Man convention was then applied to derive the typography for the highest priority drug pair names. Of 250 pairs of confusable Australian drug names, comprising 341 discrete names, 35 pairs were identified by the matrix as an 'extreme' risk if confused. The mid-type Tall Man convention was successfully applied to the majority of the prioritized drugs; some adaption of the convention was required. This systematic process for identification of confusable drug names and associated risk, followed by application of a convention for Tall Man lettering, has produced a standard now endorsed for use in clinical settings in Australia. Periodic updating is recommended to accommodate new drug names and error reports. © 2014 John Wiley & Sons, Ltd.

  3. Cost-Effectiveness of an Individualized First-Line Treatment Strategy Offering Erlotinib Based on EGFR Mutation Testing in Advanced Lung Adenocarcinoma Patients in Germany.

    Science.gov (United States)

    Schremser, Katharina; Rogowski, Wolf H; Adler-Reichel, Sigrid; Tufman, Amanda L H; Huber, Rudolf M; Stollenwerk, Björn

    2015-11-01

    Lung cancer is among the top causes of cancer-related deaths. Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors can increase progression-free survival compared with standard chemotherapy in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). The aim of the study was to evaluate the cost-effectiveness of EGFR mutation analysis and first-line therapy with erlotinib for mutation-positive patients compared with non-individualized standard chemotherapy from the perspective of German statutory health insurance. A state transition model was developed for a time horizon of 10 years (reference year 2014). Data sources were published data from the European Tarceva versus Chemotherapy (EURTAC) randomized trial for drug efficacy and safety and German cost data. We additionally performed deterministic, probabilistic and structural sensitivity analyses. The individualized strategy incurred 0.013 additional quality-adjusted life-years (QALYs) and additional costs of € 200, yielding an incremental cost-effectiveness ratio (ICER) of € 15,577/QALY. Results were most sensitive to uncertainty in survival curves and changes in utility values. Cross-validating health utility estimates with recent German data increased the ICER to about € 58,000/QALY. The probabilistic sensitivity analysis indicated that the individualized strategy is cost-effective, with a probability exceeding 50 % for a range of possible willingness-to-pay thresholds. The uncertainty of the predicted survival curves is substantial, particularly for overall survival, which was not a primary endpoint in the EURTAC study. Also, there is limited data on quality of life in metastatic lung cancer patients. Individualized therapy based on EGFR mutation status has the potential to provide a cost-effective alternative to non-individualized care for patients with advanced adenocarcinoma. Further clinical research is needed to confirm these results.

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

    Science.gov (United States)

    Kim, Miyoung; Windsor, Carol

    2015-03-01

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

  5. Surgical decortication as the first-line treatment for pleural empyema.

    Science.gov (United States)

    Shin, Jung Ar; Chang, Yoon Soo; Kim, Tae Hoon; Haam, Seok Jin; Kim, Hyung Jung; Ahn, Chul Min; Byun, Min Kwang

    2013-04-01

    The study objective was to evaluate the clinical outcomes of surgical decortication as the first line of treatment for pleural empyema. We analyzed the medical records of 111 patients who presented with empyema and were treated with simple drainage or surgical decortication as the first line of treatment at Gangnam Severance Hospital, a tertiary referral medical center in Seoul, Korea. Of 111 patients with empyema, 27 underwent surgical decortication as the first intervention. Surgical decortication showed a better treatment success rate in all study subjects (96.3%, 26/27 patients) compared with simple drainage (58.3%, 49/84 patients; P decortication resulted in a better outcome (95.0%, 19/20 patients) versus drainage (56.7%, 17/30 patients; P = .003). Surgical decortication as the first line of treatment for empyema was the best predictor of treatment success after adjustment for compounding factors (odds ratio, 14.529; 95% confidence interval, 1.715-123.074; P = .014). The first treatment choice for pleural empyema is a critical determinant of ultimate therapeutic success. After adjusting for confounding variables, surgical decortication is the optimal first treatment choice for advanced empyema. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  6. Efficacy and tolerability of vildagliptin as first line treatment in patients with diabetes type 2 in an outpatient setting.

    Science.gov (United States)

    Yavropoulou, M P; Pikilidou, M; Kotsa, K; Michopoulos, A; Papakonstantinou, E; Yovos, J G

    2015-01-01

    Inhibitors of dipeptidyl-peptidase IV are recommended as second-line therapy in type 2 diabetes (DT2), but data, as a first-line treatment in everyday clinical practice are scarce. To address this issue we conducted a 12-month, clinical study in an outpatient setting, using vildagliptin as the first-line treatment. Ninety-one drug naïve patients with DT2 started with vildagliptin monotherapy (100 mg daily) for 4 months and were scheduled to regular 4-monthly visits for 1 year. Patients received add-on treatment with metformin or metformin and glimepiride according to their glycosylated hemoglobin (HbA1c) at each study-visit. HbA1c was significantly decreased with vildagliptin monotherapy from 8.16 % ± 1.60 to 7.52 % ± 1.60, p < 0.001. Only 39 % of the patients achieved the target of HbA1c ≤ 7.0 % at the end of the 4th month. Mean change in HbA1c was significantly correlated with baseline HbA1c values (r = -0.51, p < 0.001). At the end of the study only 35 % of the patients remained on vildagliptin monotherapy while the rest required add-on treatment with metformin or metformin and sulfonylurea. Vildagliptin is well tolerated either as monotherapy or in combination but the majority of patients require add-on therapy shortly after the beginning of treatment.

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

    Science.gov (United States)

    Chuckpaiwong, Bavornrit; Phoompoung, Saravut

    2014-09-01

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

  8. Phase I/II Trial of Sorafenib in Combination with Vinorelbine as First-Line Chemotherapy for Metastatic Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Cristiano Ferrario

    Full Text Available Preclinical models have reported a synergistic interaction between sorafenib and vinorelbine. We investigated the toxicity, efficacy, and pharmacokinetics interaction of this combination as first-line treatment for patients with metastatic breast cancer.Patients were HER2-negative and treated with vinorelbine 30 mg/m2 IV days 1,8 every 21 plus daily oral sorafenib. In the phase I portion (3+3 design patients received sorafenib 200 mg BID (cohort 1 or 400 mg BID (cohort 2. In the phase II expansion, 21 more evaluable patients were planned to receive the maximum tolerated dose (MTD. Pharmacokinetic analysis was performed in 6 patients: blood concentrations were compared for each drug in the presence or absence of the other drug.In cohort 1, one patient experienced a dose-limiting toxicity (DLT (grade 3 pancreatitis, requiring the expansion of this cohort to 6 patients, without further documented DLTs. In cohort 2, one patient of six experienced a grade 4 DLT (asymptomatic rise in amylase not requiring drug discontinuation, establishing this dose level as the MTD (sorafenib 400 mg BID. After expansion at the MTD, a total of 27 patients (median age 57 were treated for a median of 8 cycles. One grade 5 febrile neutropenia occurred. With repeated cycles, 52% of patients required at least 1 dose reduction of either drug. One patient experienced a sustained grade 3 fatigue resulting in treatment discontinuation. The response rate was 30%. Median PFS was 5.7 months (95% CI 4.4-7.6, and clinical benefit (absence of disease progression at 6 months was 48%. PK analysis showed a significant interaction between the two drugs, resulting in a higher Cmax of vinorelbine in the presence of sorafenib.The combination of sorafenib and vinorelbine at full doses is feasible but not devoid of toxicity, likely also due to a significant PK interaction.ClinicalTrials.gov NCT00764972.

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

    Directory of Open Access Journals (Sweden)

    Gisele W. B. Colleoni

    2007-03-01

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

  10. Progress, innovation and regulatory science in drug development: the politics of international standard-setting.

    Science.gov (United States)

    Abraham, John; Reed, Tim

    2002-06-01

    This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and 'progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of 'technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the 'technical trajectories' of regulatory science.

  11. Updated European Association of Urology Guidelines Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer.

    Science.gov (United States)

    Powles, Thomas; Albiges, Laurence; Staehler, Michael; Bensalah, Karim; Dabestani, Saeed; Giles, Rachel H; Hofmann, Fabian; Hora, Milan; Kuczyk, Markus A; Lam, Thomas B; Marconi, Lorenzo; Merseburger, Axel S; Fernández-Pello, Sergio; Tahbaz, Rana; Volpe, Alessandro; Ljungberg, Börje; Bex, Axel

    2017-12-06

    The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline standard of care for this disease and have implications for the selection of subsequent therapies. For this reason the European Association of Urology RCC guidelines have been updated. The European Association of Urology guidelines will be updated based on the results of the phase III Checkmate-214 clinical trial. The trial showed superior survival for a combination of ipilimumab and nivolumab (IN), compared with the previous standard of care, in intermediate- and poor-risk patients with metastatic clear cell renal cell carcinoma. When IN is not safe or feasible, alternative agents such as sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at present, the data from the trial are immature in favourable-risk patients. Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of patients. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  12. Quadruple, sequential, and concomitant first-line therapies for H. pylori eradication: a prospective, randomized study.

    Science.gov (United States)

    De Francesco, Vincenzo; Pontone, Stefano; Bellesia, Annamaria; Serviddio, Gaetano; Panetta, Cristina; Palma, Rossella; Zullo, Angelo

    2017-10-18

    Current Italian guidelines recommend 10-day bismuth-based or bismuth-free (sequential and concomitant) regimens for first-line H. pylori eradication. However, comparison among these regimens is lacking in our country. To perform a 'head-to-head' comparison among these three therapies as first-line treatment for H. pylori eradication in clinical practice. This was a prospective, open-label randomized study enrolling consecutive patients diagnosed with H. pylori infection never previously treated. Patients were randomized to receive one of the following 10-day therapies: (a) Bismuth-based therapy: esomeprazole 20mg b.i.d and Pylera 3 tablets q.i.d; (b) Concomitant therapy: esomeprazole 20mg plus amoxicyllin 1,000mg, clarithromycin 500mg and tinidazole 500mg (all b.i.d.), and (c) Sequential therapy: esomeprazole 20mg plus amoxicyllin 1,000mg for 5days followed by esomeprazole 20mg plus clarithromycin 500mg and tinidazole 500mg for 5days (all b.i.d). H. pylori eradication was assessed by using UBT 4-6 weeks after the end of therapy. Overall, 187 patients were enrolled. The eradication rates achieved with Pylera, concomitant and sequential were 85.2%, 95.2%, and 93.6%, respectively, at intention to treat, and 94.5%, 96.7%, and 95.1% at per protocol analyses, without a statistically significant difference. The incidence of severe side-effects was higher with the bismuth-based therapy than with the two bismuth-free regimens (9.8% vs 1.6%; p=0.046). Bismuth-based and bismuth-free therapies are equally effective for first-line H. pylori eradication. However, bismuth therapy was more frequently interrupted for side-effects than bismuth-free therapies. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer.

    Science.gov (United States)

    Lambrechts, Sandrina; Smeets, Dominiek; Moisse, Matthieu; Braicu, Elena Ioana; Vanderstichele, Adriaan; Zhao, Hui; Van Nieuwenhuysen, Els; Berns, Els; Sehouli, Jalid; Zeillinger, Robert; Darb-Esfahani, Silvia; Cacsire Castillo-Tong, Dan; Lambrechts, Diether; Vergote, Ignace

    2016-01-01

    Most high-grade serous ovarian carcinoma (HGSOC) patients benefit from first-line platinum-based chemotherapy, but progressively develop resistance during subsequent lines. Re-activating BRCA1 or MDR1 mutations can underlie platinum resistance in end-stage patients. However, little is known about resistance mechanisms occurring after a single line of platinum, when patients still qualify for other treatments. In 31 patients with primary platinum-sensitive HGSOC, we profiled tumours collected during debulking surgery before and after first-line chemotherapy using whole-exome sequencing and single nucleotide polymorphism profiling. Besides germline BRCA1/2 mutations, we observed frequent loss-of-heterozygosity in homologous recombination (HR) genes and mutation spectra characteristic of HR-deficiency in all tumours. At relapse, tumours differed considerably from their primary counterparts. There was, however, no evidence of events reactivating the HR pathway, also not in tumours resistant to second-line platinum. Instead, a platinum score of 13 copy number regions, among other genes including MECOM, CCNE1 and ERBB2, correlated with platinum-free interval (PFI) after first-line therapy, whereas an increase of this score in recurrent tumours predicted the change in PFI during subsequent therapy. Already after a single line of platinum, there is huge variability between primary and recurrent tumours, advocating that in HGSOC biopsies need to be collected at relapse to tailor treatment options to the underlying genetic profile. Nevertheless, all primary platinum-sensitive HGSOCs remained HR-deficient, irrespective of whether they became resistant to second-line platinum, further suggesting these tumours qualify for second-line Poly APD ribose polymerase (PARP) inhibitor treatment. Finally, chromosomal instability contributes to acquired resistance after a single line of platinum therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2014-08-01

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

  15. Determinants of multidrug-resistant tuberculosis in patients who underwent first-line treatment in Addis Ababa: a case control study.

    Science.gov (United States)

    Hirpa, Selamawit; Medhin, Girmay; Girma, Belaineh; Melese, Muluken; Mekonen, Alemayehu; Suarez, Pedro; Ameni, Gobena

    2013-08-28

    Worldwide, there were 650,000 multidrug-resistant tuberculosis (MDR-TB) cases in 2010, and in 2008 the World Health Organization estimated that 150,000 deaths occurred annually due to MDR-TB. Ethiopia is 15th among the 27 MDR-TB high-burden countries. This study identifies factors associated with the occurrence of MDR-TB in patients who underwent first-line TB treatment in Addis Ababa City. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa from 1 November 2011 to February 30, 2012. Cases were MDR-TB patients who were confirmed with culture and drug-susceptibility testing and were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009- 28 February 2010, in five health centers of Addis Ababa City. Accordingly, 134 cases and an equal number of controls were included in this study. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4-34.3); interruption of treatment of at least a day (AOR = 13.1, 95% CI 3.0-56.6); duration of treatment between 2 and 7 months (AOR = 14.8, 95% CI 2.3-96.4); and retreatment with the Category II regimen (P = 0.000). In the current study, HIV infection was not significantly associated with the occurrence of MDR-TB. Patients who were not in strict DOTS programs and did not adhere to first-line TB treatment and patients who experienced side effects during first-line treatment and Category II retreatment were at significantly increased risk of developing MDR-TB. The DOTS program should, therefore, be strengthened to increase

  16. 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

    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......-five patients were included in the dose-escalation study, which defined 40 mg/m(2) as the MTD. Neutropenia of short duration and autonomic neuropathy causing constipation were the most common dose-limiting toxicities. At the 35 mg/m(2) dose-level 60 patients were included in total. Seven (12%; 95% CI 6 to 22...

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

    Directory of Open Access Journals (Sweden)

    Yasemin Altuner Torun

    2011-03-01

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

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

    DEFF Research Database (Denmark)

    Novovic, Srdan; Semb, Synne; Olsen, Henrik

    2012-01-01

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

  19. Mobilizing First-Line Managers as Organizational Strategy Makers: The Case of Environmentally Sustainable Operations

    OpenAIRE

    Gjøsæter, Åge

    2013-01-01

    The purpose of the paper is to investigate how first-line managers are mobilized as organizational strategy makers. The research case is a campaign launched by a Norwegian shipping company servicing the petroleum industry. The strategic idea on which the campaign was based was to operate the company`s fleet of offshore service vessels in an environmentally sustainable way, to be realized by carrying out fuel-saving operations on board the vessels. A strategic idea is supposed to set out a vie...

  20. Recurrent glioblastomas in the elderly after maximal first-line treatment: does preserved overall condition warrant a maximal second-line treatment?

    Science.gov (United States)

    Zanello, Marc; Roux, Alexandre; Ursu, Renata; Peeters, Sophie; Bauchet, Luc; Noel, Georges; Guyotat, Jacques; Le Reste, Pierre-Jean; Faillot, Thierry; Litre, Fabien; Desse, Nicolas; Emery, Evelyne; Petit, Antoine; Peltier, Johann; Voirin, Jimmy; Caire, François; Barat, Jean-Luc; Vignes, Jean-Rodolphe; Menei, Philippe; Langlois, Olivier; Dezamis, Edouard; Carpentier, Antoine; Dam Hieu, Phong; Metellus, Philippe; Pallud, Johan

    2017-11-01

    A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p oncological treatment from recurrence (p patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

  1. First-line bevacizumab-containing therapy for triple-negative breast cancer: analysis of 585 patients treated in the ATHENA study.

    Science.gov (United States)

    Thomssen, Christoph; Pierga, Jean-Yves; Pritchard, Kathleen I; Biganzoli, Laura; Cortes-Funes, Hernan; Petráková, Katarína; Kaufman, Bella; Duenne, Anja; Smith, Ian

    2012-01-01

    The prognosis for patients with triple-negative breast cancer (TNBC) is poor and treatment options are limited. Bevacizumab improves the efficacy of standard first-line therapy in locally recurrent/metastatic breast cancer (LR/mBC). The benefit of bevacizumab seen in patients with TNBC appears similar to that observed in the overall population. We conducted an exploratory analysis of patients with TNBC treated in the single-arm routine oncology practice ATHENA study. Patients with previously untreated LR/mBC received standard first-line chemotherapy combined with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks, until progression, unacceptable toxicity, or patient/physician decision). Of 2,264 patients treated in ATHENA, 585 (26%) had TNBC. Most patients received single-agent taxane with bevacizumab. In the TNBC subgroup, the overall response rate was 49%, including complete responses in 10%; only 16% had primary resistant disease. Median time to progression was 7.2 months (95% CI 6.6-7.8) and median overall survival was 18.3 months (95% CI 16.4-19.7). The 1-year overall survival rate was 60%. The safety profile in TNBC was consistent with results in the overall population. This exploratory subgroup analysis suggests that first-line chemotherapy in combination with bevacizumab is an active regimen in patients with metastatic TNBC. Copyright © 2012 S. Karger AG, Basel.

  2. Safety and efficacy of vinorelbine in combination with pertuzumab and trastuzumab for first-line treatment of patients with HER2-positive locally advanced or metastatic breast cancer

    DEFF Research Database (Denmark)

    Perez, Edith A; López-Vega, José Manuel; Petit, Thierry

    2016-01-01

    BACKGROUND: Pertuzumab, trastuzumab, and docetaxel is standard of care for first-line treatment of HER2-positive metastatic breast cancer (MBC). However, alternative chemotherapy partners are required to align with patient/physician preferences and to increase treatment flexibility. We report.......2% (95% CI 63.8-82.9) in intent-to-treat patients with measurable disease (89/106 [84.0%]). Median PFS was 14.3 months (95% CI 11.2-17.5) in the intent-to-treat population. Treatment was reasonably well tolerated, with no unexpected toxicities. Diarrhea (61/106 patients [57.5%]) and neutropenia (54.......0%) had AEs suggestive of congestive heart failure; however, there were no confirmed cases. CONCLUSIONS: The vinorelbine, pertuzumab, and trastuzumab combination is active and reasonably well tolerated. This regimen offers an alternative for patients who cannot receive docetaxel for first-line treatment...

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

    Directory of Open Access Journals (Sweden)

    Bryan Soh, MBBS, BBiomedSci, PGDipSurgAnat

    2017-05-01

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

  4. Early identification of resistance to first-line single-agent methotrexate in patients with persistent trophoblastic disease.

    NARCIS (Netherlands)

    Trommel, N.E. van; Massuger, L.F.A.G.; Schijf, C.P.T.; Kate-Booij, M.J.; Sweep, C.G.J.; Thomas, C.M.G.

    2006-01-01

    PURPOSE: A generally accepted definition for resistance to first-line single-agent chemotherapy for persistent trophoblastic disease (PTD) is lacking. In the present study, a normogram for serum human chorionic gonadotropin (hCG) from patients with normalization of serum hCG after first-line

  5. High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi.

    Science.gov (United States)

    Bwijo, B; Kaneko, A; Takechi, M; Zungu, I L; Moriyama, Y; Lum, J K; Tsukahara, T; Mita, T; Takahashi, N; Bergqvist, Y; Björkman, A; Kobayakawa, T

    2003-03-01

    Malawi changed its national policy for malaria treatment in 1993, becoming the first country in Africa to replace chloroquine by sulfadoxine and pyrimethamine combination (SP) as the first-line drug for uncomplicated malaria. Seven years after this change, we investigated the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations, known to be associated with decreased sensitivity to SP, in 173 asymptomatic Plasmodium falciparum infections from Salima, Malawi. A high prevalence rate (78%) of parasites with triple Asn-108/Ile-51/Arg-59 dhfr and double Gly-437/Glu-540 dhps mutations was found. This 'quintuple mutant' is considered as a molecular marker for clinical failure of SP treatment of P. falciparum malaria. A total of 11 different dhfr and dhps combinations were detected, 3 of which were not previously reported. Nineteen isolates contained the single Glu-540 mutant dhps, while no isolate contained the single Gly-437 mutant dhps, an unexpected finding since Gly-437 are mostly assumed to be one of the first mutations commonly selected under sulfadoxine pressure. Two isolates contained the dhps single or double mutant coupled with dhfr wild-type. The high prevalence rates of the three dhfr mutations in our study were consistent with a previous survey in 1995 in Karonga, Malawi, whereas the prevalences of dhps mutations had increased, most probably as a result of the wide use of SP. A total of 52 P. falciparum isolates were also investigated for pyrimethamine and sulfadoxine/pyrimethamine activity against parasite growth according to WHO in vitro standard protocol. A pyrimethamine resistant profile was found. When pyrimethamine was combined with sulfadoxine, the mean EC(50) value decreased to less than one tenth of the pyrimethamine alone level. This synergistic activity may be explained by sulfadoxine inhibition of dhps despite the double mutations in the dhps genes, which would interact with pyrimethamine acting to block the

  6. ADEpedia: a scalable and standardized knowledge base of Adverse Drug Events using semantic web technology.

    Science.gov (United States)

    Jiang, Guoqian; Solbrig, Harold R; Chute, Christopher G

    2011-01-01

    A source of semantically coded Adverse Drug Event (ADE) data can be useful for identifying common phenotypes related to ADEs. We proposed a comprehensive framework for building a standardized ADE knowledge base (called ADEpedia) through combining ontology-based approach with semantic web technology. The framework comprises four primary modules: 1) an XML2RDF transformation module; 2) a data normalization module based on NCBO Open Biomedical Annotator; 3) a RDF store based persistence module; and 4) a front-end module based on a Semantic Wiki for the review and curation. A prototype is successfully implemented to demonstrate the capability of the system to integrate multiple drug data and ontology resources and open web services for the ADE data standardization. A preliminary evaluation is performed to demonstrate the usefulness of the system, including the performance of the NCBO annotator. In conclusion, the semantic web technology provides a highly scalable framework for ADE data source integration and standard query service.

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

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Alain; Girish, Baragur V.; de Baere, Thierry [Service de Radiologie Interventionnelle, Institut Gustave Roussy, rue Camille Desmoulins 39, 94805 Villejuif Cedex (France); Baudin, Eric; Schlumberger, Martin [Service de Medecine Nucleaire, Institut Gustave Roussy, rue Camille Desmoulins 39, 94805 Villejuif Cedex (France); Boige, Valerie; Ducreux, Michel [Service d' Oncologie Digestive, Institut Gustave Roussy, rue Camille Desmoulins 39, 94805 Villejuif Cedex (France); Elias, Dominique; Lasser, Philippe [Service de Chirurgie Digestive, Institut Gustave Roussy, rue Camille Desmoulins 39, 94805 Villejuif Cedex (France)

    2003-01-01

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

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

    Science.gov (United States)

    Macphee, Maura; Suryaprakash, Nitya

    2012-03-01

    To examine nurse leaders' change management projects within British Columbia, Canada. British Columbia Nursing Leadership Institute 2007-10 attendees worked on year-long change management initiatives/projects of importance to their respective health-care institutions. Most leaders were in first-line positions with leaders' project reports (N = 133) were content analysed for specific themes: types of projects; scope of projects (e.g. unit or local level, departmental, institutional); influence targets or key stakeholder groups targeted by the projects; leadership successes and challenges. Of study participants, 77% successfully completed their projects. Staff tool and resource development and existing services improvement were major project types. Care delivery teams were the major influence targets. Only 25% of projects were at the unit level. Many projects had broader scopes, such as institutional levels. Participants cited multiple leadership successes, including enhanced leadership styles and organizational skills. First-line nurse leaders were able to successfully manage projects beyond their traditional scope of responsibilities. The majority of projects dealt with staff needs and healthcare restructuring initiatives. Constant change is a global reality. Change management, a universal competency, must be included in leadership development programmes. © 2011 Blackwell Publishing Ltd.

  9. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2009-08-01

    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  10. No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

    Science.gov (United States)

    Perrier, Marine; Visseaux, Benoit; Landman, Roland; Joly, Véronique; Todesco, Eve; Yazdanpanah, Yazdan; Calvez, Vincent; Marcelin, Anne-Geneviève; Descamps, Diane; Charpentier, Charlotte

    2018-01-01

    To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen. In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list). Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40). This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

  11. Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

    Science.gov (United States)

    Kräenbring, Jona; Monzon Penza, Tika; Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

    2014-01-01

    The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

  12. Accuracy and Completeness of Drug Information in Wikipedia: A Comparison with Standard Textbooks of Pharmacology

    Science.gov (United States)

    Gutmann, Joanna; Muehlich, Susanne; Zolk, Oliver; Wojnowski, Leszek; Maas, Renke; Engelhardt, Stefan; Sarikas, Antonio

    2014-01-01

    The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7%±0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8±1.5% (p<0.001). Completeness varied in-between categories, and was lowest in the category “pharmacokinetics” (68.0%±4.2%; p<0.001) and highest in the category “indication” (91.3%±2.0%) when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6±1.6 references and 262.8±37.4 edits performed by 142.7±17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education. PMID:25250889

  13. Accuracy and completeness of drug information in Wikipedia: a comparison with standard textbooks of pharmacology.

    Directory of Open Access Journals (Sweden)

    Jona Kräenbring

    Full Text Available The online resource Wikipedia is increasingly used by students for knowledge acquisition and learning. However, the lack of a formal editorial review and the heterogeneous expertise of contributors often results in skepticism by educators whether Wikipedia should be recommended to students as an information source. In this study we systematically analyzed the accuracy and completeness of drug information in the German and English language versions of Wikipedia in comparison to standard textbooks of pharmacology. In addition, references, revision history and readability were evaluated. Analysis of readability was performed using the Amstad readability index and the Erste Wiener Sachtextformel. The data on indication, mechanism of action, pharmacokinetics, adverse effects and contraindications for 100 curricular drugs were retrieved from standard German textbooks of general pharmacology and compared with the corresponding articles in the German language version of Wikipedia. Quantitative analysis revealed that accuracy of drug information in Wikipedia was 99.7% ± 0.2% when compared to the textbook data. The overall completeness of drug information in Wikipedia was 83.8 ± 1.5% (p < 0.001. Completeness varied in-between categories, and was lowest in the category "pharmacokinetics" (68.0% ± 4.2%; p < 0.001 and highest in the category "indication" (91.3% ± 2.0% when compared to the textbook data overlap. Similar results were obtained for the English language version of Wikipedia. Of the drug information missing in Wikipedia, 62.5% was rated as didactically non-relevant in a qualitative re-evaluation study. Drug articles in Wikipedia had an average of 14.6 ± 1.6 references and 262.8 ± 37.4 edits performed by 142.7 ± 17.6 editors. Both Wikipedia and textbooks samples had comparable, low readability. Our study suggests that Wikipedia is an accurate and comprehensive source of drug-related information for undergraduate medical education.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Beck JT

    2015-12-01

    Full Text Available J Thaddeus Beck Highlands Oncology Group, Fayetteville, AR, USA Abstract: Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year ­survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2 study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. Keywords: mammalian target of rapamycin, everolimus, hormone receptor–positive breast cancer, first-line

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

    DEFF Research Database (Denmark)

    Marthin, J K; Nielsen, K G

    2011-01-01

    . 282 subjects, 117 consecutive referrals, 59 PCDs, 49 CF patients and 57 healthy subjects, were included. All methods separated significantly between PCD and non-PCD, including CF with reliability, in ranking order BH-nNO>OE-R-nNO>TB-nNO. Acceptability in children ranked in reverse order. A problematic...... high fraction (39%) of false positive TB-nNO was found in young children. An unexpected large fraction (6.8%) of PCDs had nNO values above cut-off. nNO is a helpful first-line tool in real-life PCD work-up in all age groups if the sampling method is chosen according to age. nNO can be misleading...

  17. Human african trypanosomiasis diagnosis in first-line health services of endemic countries, a systematic review.

    Directory of Open Access Journals (Sweden)

    Patrick Mitashi

    Full Text Available While the incidence of Human African Trypanosomiasis (HAT is decreasing, the control approach is shifting from active population screening by mobile teams to passive case detection in primary care centers. We conducted a systematic review of the literature between 1970 and 2011 to assess which diagnostic tools are most suitable for use in first-line health facilities in endemic countries. Our search retrieved 16 different screening and confirmation tests for HAT. The thermostable format of the Card Agglutination Test for Trypanosomiasis (CATT test was the most appropriate screening test. Lateral flow antibody detection tests could become alternative screening tests in the near future. Confirmation of HAT diagnosis still depends on visualizing the parasite in direct microscopy. All other currently available confirmation tests are either technically too demanding and/or lack sensitivity and thus rather inappropriate for use at health center level. Novel applications of molecular tests may have potential for use at district hospital level.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  19. First-line Bismuth-containing Five-day Concomitant Quintuple Therapy for Helicobacter Pylori Eradication.

    Science.gov (United States)

    Dolapcioglu, Can; Sayiner, Mehmet; Akkus, Esra Elif; Kural, Abdulaziz; Dolapcioglu, Hatice; Dabak, Resat; Ahishali, Emel

    2016-04-01

    Widespread use of antibiotics has resulted in increased rates of antibiotic resistance and decreased rates of Helicobacter pylori (H. pylori) eradication, leading to a search for newer therapeutic options. This study aimed to examine the efficacy, tolerability, and patient compliance of a first-line bismuth-containing 5-day concomitant quintuple therapy. This prospective study included 144 eradication treatment naïve H. pylori positive patients with dyspeptic complaints. Patients received the following concomitant quintuple therapy for 5 days: bismuth subcitrate 300 mg q.i.d, omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. Eradication was assessed with H. pylori stool antigen test or urea-breath test 6 weeks after the completion of therapy. Treatment compliance rate in this study was 97.2%. Intention to treat and per-protocol eradication rates were 134/144 (93.1%, 95% CI, 88.9-97.2) and 134/140 (95.7%, 95% CI, 92.2-98.6), respectively. Side effect was reported by 8.5% of the patients that attended follow-up visits, including epigastric pain (2.8%), nausea/vomiting (2.1%), diarrhea (1.4%), taste disturbance (1.4%), and fatigue (0.7%). Bismuth-containing, short course, quintuple concomitant therapy appears to be an effective and safe therapeutic option for the first-line H. pylori eradication, particularly in populations with high resistance. © 2015 John Wiley & Sons Ltd.

  20. Systematic review: What is the best first-line approach for cesarean section ectopic pregnancy?

    Science.gov (United States)

    Kanat-Pektas, Mine; Bodur, Serkan; Dundar, Ozgur; Bakır, Vuslat Lale

    2016-04-01

    This systematic review aims to analyze the case reports, case series, or clinical studies describing the women with cesarean scar ectopic pregnancy (CSEP), and thus, to determine the efficacy and safety of different primary treatment modalities in the management of CSEP. A thorough search of electronic databases showed that 274 articles on CSEP were published between January 1978 and April 2014. Systemic methotrexate, uterine artery embolization, dilatation and curettage (D&C), hysterotomy, and hysteroscopy were the most frequently adopted first-line approaches. The success rates of systemic methotrexate, uterine artery embolization, hysteroscopy, D&C, and hysterotomy were 8.7%, 18.3%, 39.1%, 61.6%, and 92.1%, respectively. The hysterectomy rates were 3.6%, 1.1%, 0.0%, 7.3%, and 1.7% in CSEP cases that were treated by systemic methotrexate, uterine artery embolization, hysteroscopy, D&C, and hysterotomy, respectively. The ability to achieve a subsequent term pregnancy is related to successful systemic methotrexate treatment (p = 0.001) or hysterotomy (p = 0.009). Future term pregnancy was significantly more frequent in the hysterotomy group (p = 0.001). Hysteroscopy and laparoscopic hysterotomy are safe and efficient surgical procedures that can be adopted as primary treatment modalities for CSEP. Uterine artery embolization should be reserved for cases with significant bleeding and/or a high suspicion index for arteriovenous malformation. Systemic methotrexate and D&C are not recommended as first-line approaches for CSEP, as these procedures are associated with high complication and hysterectomy rates. Copyright © 2016. Published by Elsevier B.V.

  1. Physical therapists as first-line diagnosticians for traumatic acute rotator cuff tears: a prospective study.

    Science.gov (United States)

    Aagaard, Knut E; Hänninen, Jonas; Abu-Zidan, Fikri M; Lunsjö, Karl

    2017-11-29

    Early diagnosis of traumatic acute full-thickness rotator cuff tears (FTRCT) is important to offer early surgical repair. Late repairs following fatty infiltration of the rotator cuff muscles have less favorable results. We think that physical therapists are valuable diagnosticians in a screening process. The objective of this study was to evaluate the usefulness of physical therapists as first-line diagnosticians in detecting acute traumatic FTRCT. Between November 2010 and January 2014, 394 consecutive patients having an age between 18 and 75 years who sought medical care because of acute shoulder trauma with acute onset of pain, limited abduction and negative plain radiographs were included in the study. A clinical assessment was conducted by a physical therapist 1 week after the trauma. The patients were divided into three groups by the physical therapist according to the findings: FTRCT (Group I, n = 122); sprain (Group II, n = 62); or other specific diagnoses (Group III, n = 210). Group III patients were discharged and excluded from the study. Magnetic Resonance Imaging shoulder was performed for all Group I patients and for all patients with persistent symptoms in Group II. 79/184 patients had FTRCTs documented by MRI in groups I and II. The clinical assessment of the physical therapist had a sensitivity of 85%, specificity of 68%, and usefulness index of 0.45 (> 0.35 considered useful) for diagnosing FTRCT. Physical therapists can be useful as first-line diagnosticians in detecting traumatic FTRCT.

  2. First-line sunitinib or pazopanib in metastatic renal cell carcinoma: The Canadian experience.

    Science.gov (United States)

    Lalani, Aly-Khan A; Li, Haocheng; Heng, Daniel Y C; Wood, Lori; Kalirai, Austin; Bjarnason, Georg A; Sim, Hao-Wen; Kollmannsberger, Christian K; Kapoor, Anil; Hotte, Sebastien J; Vanhuyse, Marie; Czaykowski, Piotr; Reaume, M Neil; Soulieres, Denis; Venner, Peter; North, Scott; Basappa, Naveen S

    2017-01-01

    Clinical trial data has shown pazopanib to be non-inferior in overall survival (OS) compared to sunitinib as first-line treatment for metastatic renal cell carcinoma (mRCC). The purpose of this study was to evaluate outcomes and compare dose-modifying toxicities of mRCC patients treated with suntinib or pazopanib in the real-world setting. Data were collected on mRCC patients using the prospective Canadian Kidney Cancer Information System (CKCis) database from January 2011 to November 2015. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method. We identified 670 patients treated with sunitinib (n=577) and pazopanib (n=93). There were no significant differences in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups (p=0.807). Patients treated with sunitinib had improved OS compared with pazopanib (median 31.7 vs. 20.6 months, p=0.028; adjusted hazard ratio [aHR] 0.60; 95% confidence interval [CI] 0.38-0.94). Time to treatment failure (TTF) was numerically, but not statistically, improved with sunitinib (medians 11.0 vs. 8.4 months, p=0.130; aHR 0.87; 95% CI 0.59-1.28). Outcomes with individualized dosing on sunitinib were unavailable for this analysis. Patients treated with sunitinib had a higher incidence of mucositis, hand-foot syndrome, and gastroesophageal reflux disease; patients treated with pazopanib had a higher incidence of hepatotoxicity. In Canadian patients with mRCC, treatment with sunitinib appears to be associated with an improved OS compared to pazopanib in the first-line setting. Patient selection factors and the contemporary practice of individualized dosing with sunitinib may contribute to these real-world outcomes and warrant further investigation.

  3. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  4. Spanish Compliance With Guidelines for Prescribing Four Drugs in the Intensive Phase of Standard Tuberculosis Treatment.

    Science.gov (United States)

    García-García, José-María; Rodrigo, Teresa; Casals, Martí; Ruiz-Manzano, Juan; Pascual-Pascual, Teresa; Caylà, Joan A

    2016-05-01

    International and Spanish guidelines recommend a 4-drug regimen in the intensive treatment of tuberculosis (TB). The aim of our study was to determine if these recommendations are followed in Spain, and the factors associated with the use of 3 drugs (standard regimen without ethambutol). Observational, multicenter, retrospective analysis of data from patients diagnosed with TB in practically all Spanish Autonomous Communities between 2007 and 2102. Factors associated with the use of 3 drugs were analyzed using logistic regression, and odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. A total of 3,189 patients were included, 1,413 (44.3%) of whom received 3 drugs. The percentage of 3-drug users among patients with positive sputum smear was 41.2%; among patients with resistance to at least 1 drug, 36.1%; among HIV-infected patients, 31.4%; and among immigrants, 24.8%. Factors associated with the use of 3 drugs were: female sex (OR=1.18; CI: 1.00-1.39); native Spanish (OR=3.09; CI: 2.58-3.70); retired (OR=1.42; CI: 1.14-1.77); homeless (OR=3.10; CI: 1.52-6.43); living alone (OR=1.62; CI: 1.11-2.36); living in a family (OR=1.97; CI: 1.48-2.65); seen by specialists in the region (OR=1.37; CI: 1.10;1.70); no HIV infection (OR=1.63; CI: 1.09-2.48); and negative sputum smear with positive culture (OR=1.59; CI: 1.25-2.02). A large proportion of TB patients receive intensive treatment with 3 drugs. TB treatment recommendations should be followed, both in routine clinical practice and by the National Plan for Prevention and Control of Tuberculosis in Spain. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

  5. Oral Teicoplanin as an Alternative First-Line Regimen in Clostridium difficile Infection in Elderly Patients: A Case Series.

    Science.gov (United States)

    Davido, Benjamin; Leplay, Céline; Bouchand, Frédérique; Dinh, Aurélien; Villart, Maryvonne; Le Quintrec, Jean-Laurent; Teillet, Laurent; Salomon, Jérôme; Michelon, Hugues

    2017-07-01

    Elderly patients are more susceptible to Clostridium difficile infections (CDIs). Despite existing guidelines, there is no specific treatment for CDI in geriatrics. Vancomycin is commonly used in the treatment of CDI. Teicoplanin is an alternative glycopeptide which recently received marketing authorization approval for CDI in Europe. Evaluate the potential interest of oral teicoplanin and assess whether such treatment could potentially become an alternative treatment in mild to severe CDIs in elderly patients. A prospective monocentric study was conducted over 10 months (from December 2015 to October 2016) in a geriatric unit (Sainte Périne, AP-HP, Paris, France). According to the remote infectious disease specialist, some hospitalized patients suffering from CDI and aged over 65 years received oral teicoplanin 200 mg twice a day (highest dose recommended). The clinical response to teicoplanin and relapses after treatment were evaluated. Patients were monitored up to 90 days after teicoplanin administration, and analyzed in non-responder imputation analysis. Eleven patients received teicoplanin among 19 CDIs during the study time period. In non-responder imputation analysis, 90.9% (n = 10) successfully responded to oral teicoplanin. The rate of relapse observed after a 90-day follow-up was 36.4%. Patients reported no drug-related adverse effects. Oral teicoplanin is a glycopeptide that could be proposed as an alternative to other recommended drugs for CDI. In our case series, teicoplanin seems to be an effective therapy as a first-line regimen for CDI in geriatrics. Such treatment has good acceptability in geriatrics, considering it can be taken orally twice a day.

  6. Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

    Science.gov (United States)

    Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

    2017-06-23

    The equilibrium dissociation constant (KD) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the KD value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative KD values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The KD values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the KD values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. An economic comparison of chloroquine and sulfadoxine-pyrimethamine as first-line treatment for malaria in South Africa: development of a model for estimating recurrent direct costs.

    Science.gov (United States)

    Wilkins, J J; Folb, P I; Valentine, N; Barnes, K I

    2002-01-01

    The relative cost-effectiveness of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) as first-line antimalarial therapy in southern Africa is of great interest to policymakers, clinicians and researchers in the subregion. A model was developed to access the cost-effectiveness of replacing CQ with SP as first-line treatment in Mpumalanga, South Africa, where malaria is seasonal and the population is non-immune. In-vivo drug resistance levels were used to derive a 'resistance variable' for each drug, which was used to compare the costs to the public healthcare provider associated with either therapeutic option. Costs including drugs, staff time, transport, maintenance, utilities, training and consumables were determined and subjected to Monte Carlo simulation and subsequent analysis to generate an average cost-effectiveness ratio (ACER) with confidence intervals for each drug. SP was found to be 4.8 (95% CI 3.3-6.7) times more cost-effective than CQ in Mpumalanga at 1997 resistance levels and costs, despite the far greater cost per treatment course of SP (US$ 4.02 as opposed to US$ 0.22 for CQ) in South Africa. At the price of SP in Kenya and Uganda (US$ 0.47-4.80 per treatment course), the ACER for SP does not change materially, increasing to between 5.1 and 5.6. Resistance emerged as the factor that most influenced the ACER of a specific drug. Indirect costs, compliance, changes in effectiveness and costs over time and costs of adverse events were not included in the model owing to paucity of data and logistical difficulties. Since most of these are likely to be similar in both drug models, the relative ACER is unlikely to be significantly altered by their inclusion.

  8. Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis of Randomized Trials.

    Science.gov (United States)

    Ford, Nathan; Shubber, Zara; Pozniak, Anton; Vitoria, Marco; Doherty, Meg; Kirby, Catherine; Calmy, Alexandra

    2015-08-01

    Efavirenz (EFV) is widely used for the treatment of antiretroviral-naive HIV-positive individuals, but there are concerns about the risk of adverse neuropsychiatric events. We systematically reviewed the safety of EFV in first-line therapy. Four databases were searched until October 2014 for randomized trials comparing EFV against non-EFV-based regimens for the treatment of antiretroviral-naive HIV-positive adults and children. The primary outcome was drug discontinuation as a result of any adverse event. Relative risks and proportions were pooled using random-effects meta-analysis. Forty-two trials were included for review. A lower relative and absolute risk of discontinuations due to adverse drug reactions was seen with EFV compared to nevirapine. The relative and absolute risk of discontinuation was greater for EFV compared with low-dose EFV, rilpivirine, tenofovir, atazanavir, and maraviroc. The relative risk of discontinuation was greater for EFV compared with dolutegravir and raltegravir, but absolute risks were not significantly different. There was no difference in the risk of any severe clinical adverse events for any comparison. With the exception of dizziness, fewer than 10% of patients exposed to EFV experienced any other specific type of neuropsychiatric event. No suicides were reported. This review found that over 90% of patients remained on an EFV-based first-line regimen after an average follow-up time of 78 weeks. The relative risk of discontinuations due to adverse events was higher for EFV compared with most other first-line options, but absolute differences were less than 5% for all comparisons.

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

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    Antonio Di Biagio

    2014-11-01

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

  10. New treatment strategies for pulmonary sarcoidosis : antimetabolites, biological drugs, and other treatment approaches

    NARCIS (Netherlands)

    Baughman, Robert P; Grutters, JC|info:eu-repo/dai/nl/258116129

    2015-01-01

    About half of patients with sarcoidosis will need systemic therapy for their disease. Oral glucocorticoids are the standard first-line treatment for sarcoidosis. With time, patients might develop substantial morbidity from long-term use of high doses of these drugs. We propose a step-wise approach

  11. [Epilepsy in Lao Popular Democratic Republic: difficult procurement of a first-line antiepileptic contributes to widening the treatment gap].

    Science.gov (United States)

    Chivorakoun, P; Harimanana, A; Clavel, S; Jousseaume, S; Barennes, H

    2012-03-01

    In Laos, over 95% of people with epilepsy (PWE) do not receive a proper treatment. Traditional beliefs and practices have long explained this wide treatment gap. From 2008 to 2010 we evaluated the procurement process for phenobarbital, the leading first-line antiepileptic drug (AED) in Laos, and its availability at a national scale as a potential additional major cause of this treatment gap in Laos. Data were drawn from several surveys conducted from 2008 to 2010: (i) semi structured interviews of key persons from the Ministry of Health and from pharmaceutical factories, wholesalers, pharmacists, neurologists, psychiatrists, and non-governmental organisations; (ii) retrospective survey of AED prescriptions in three main hospitals of Vientiane the capital city during two randomised weeks from June to August 2009; (iii) self-administered questionnaires of pediatricians regarding their knowledge about phenobarbital; (iv) a national survey of the AED availability in pharmacies and drug shops in 16/17 provinces, 16 districts and 96 villages (multistage randomised survey) in 2010 and a survey among the population in 2009. Phenobarbital is imported in Laos via a carefully controlled importation process either as raw material to be processed by factory N(o) 2 or in the form of tablets. The International Narcotics Control Board (Vienne) delivers a yearly quota of 25kg of raw phenobarbital to the Food and Drug department (FDA). This allows the production of 245000 tablets per year (around 671 annual adult treatments). The overall importation process for phenobarbital lasts 6months. Grade 1 pharmacists (mostly located in urban areas) and regional and district hospitals are authorized to deliver phenobarbital. The cost of phenobarbital ranged from 0.11 to 0.2US dollars/tablet per day (39 to 67US dollars per year). High cost of transportation and increased cost of phenobarbital (5- to 10-fold greater than the international market) contribute to reduce access to treatment. Needs

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

    Science.gov (United States)

    Kleiber, Niina; de Wildt, Saskia N; Cortina, Gérard; Clifford, Michael; Ducruet, Thierry; Tibboel, Dick; Millar, Johnny

    2016-04-01

    To determine the cardiovascular tolerance of clonidine used as a first-line sedative after cardiac surgery in small infants. Retrospective chart review. A tertiary and quaternary referral cardiac PICU. All infants younger than 2 months who received a clonidine infusion for sedation after cardiac surgery from October 2011 to July 2013. None. Heart rate, blood pressure, central venous and left atrial pressure, vasoactive inotropic score, volume of fluid bolus, and lactate and central mixed venous saturation were assessed. Preinfusion values were compared with postinfusion values. Of 224 potentially eligible patients, only 23 infants met inclusion criteria, as most patients only received high doses of morphine and some received midazolam instead of clonidine. Clonidine administration was started at a median of 12 hours after surgery (Q1-Q3, 5-23), and infusion rate was 0.5-2 μg/kg/hr for a median duration of 30 hours (Q1-Q3, 12-54). Heart rate decreased (maximal mean decrease: 12% [149 beats/min (SD, 17) to 131 beats/min (SD, 17)]; p sedative added to morphine in selected patients seems hemodynamically safe. The observed decrease in heart rate and diastolic blood pressure seems of minimal clinical importance as all other hemodynamic variables remained stable or improved. The safety of clonidine given early after cardiac surgery as alternative to midazolam merits further study.

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

    Science.gov (United States)

    Sepehri, Mitra; Jørgensen, Bo; Serup, Jørgen

    2015-10-01

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

  14. Leadership and management skills of first-line managers of elderly care and their work environment.

    Science.gov (United States)

    Abdelrazek, Fathya; Skytt, Bernice; Aly, Magda; El-Sabour, Mona Abd; Ibrahim, Naglaa; Engström, Maria

    2010-09-01

    To study the leadership and management skills of first-line managers (FLMs) of elderly care and their work environment in Egypt and Sweden. FLMs in Egypt and Sweden are directly responsible for staff and quality of care. However, FLMs in Sweden, in elderly care, have smaller units/organizations to manage than do their colleagues in Egypt. Furthermore, family care of the elderly has been the norm in Egypt, but in recent years institutional care has increased, whereas in Sweden, residential living homes have existed for a longer period. A convenience sample of FLMs, 49 from Egypt and 49 from Sweden, answered a questionnaire measuring leadership and management skills, structural and psychological empowerment, job satisfaction and psychosomatic health. In both countries, FLMs' perceptions of their leadership and management skills and psychological empowerment were quite high, whereas scores for job satisfaction and psychosomatic health were lower. FLMs had higher values in several factors/study variables in Egypt compared with in Sweden. The work environment, both in Egypt and Sweden, needs to be improved to increase FLMs' job satisfaction and decrease stress. The cultural differences and levels of management have an effect on the differences between the two countries. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

  15. First-Line Helicobacter pylori Eradication with Vonoprazan, Clarithromycin, and Metronidazole in Patients Allergic to Penicillin

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    Soichiro Sue

    2017-01-01

    Full Text Available Aim. To assess the efficacy of 7-day first-line Helicobacter pylori eradication with vonoprazan (VPZ, clarithromycin (CAM, and metronidazole (MNZ in patients with penicillin allergy. Methods. Patients with penicillin allergy, diagnosed with Helicobacter pylori infection and did not have history of Helicobacter pylori eradication, were eligible for the study. Twenty patients were prospectively treated with 20 mg VPZ twice daily, 200 or 400 mg CAM twice daily, and 250 mg MNZ twice daily for 7 days. We also collected the data from 30 patients retrospectively treated with proton pump inhibitor (PPI, CAM, and MNZ. Safety was evaluated in patients completing an adverse effect questionnaire. Results. Both the intention-to-treat and per-protocol effectiveness of VPZ-based eradication were 100% (95% CI: 86.1–100%; n=20. The eradication rates of PPI-based regimen were 83.3% (95% CI: 65.3–94.4% in the ITT and 82.7% (95% CI: 64.2–94.2% in the PP analyses. Abdominal fullness was more frequent in VCM compared to PCM. However, all patients with VCM regimen had taken 100% of their course of medication. Conclusion. Triple therapy with VPZ, CAM, and MNZ is well tolerated and effective for eradicating Helicobacter pylori in patients allergic to penicillin. This study was registered in the UMIN Clinical Trials Registry as UMIN000016335.

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

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    Allison T Siebern

    2011-02-01

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

  17. First-line rescue system of Chinese army in non-warfare military operations

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    Wei ZHAO

    2016-03-01

    Full Text Available In the 21st century, non traditional security threats have become increasingly prominent, non warfare military activity has become general trend of global military development, and it has become the main activities of the peacetime arm forces in all countries. Therefore, to carry out and strengthen the medical support in non-war military operations is a long-term strategic task of Chinese Army medical service. The concept about non-war military activities and characteristics of medical support, and the existing problems, and measures of establishment of first-line rescue system are presented in this paper. Under the reformation of military affairs, the front-line ambulance system in non-war military action will work closely around the key security such as disaster relief, peacekeeping operations, public health emergencies and major events. It is necessary to learn the advanced experience from developed countries, and continuously deepen medical security work in non-war military operations on the basis of "non-combat" and "war"-oriented concept. DOI: 10.11855/j.issn.0577-7402.2016.01.17

  18. A review on the status of quality control and standardization of herbal drugs in India

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    Anju Dhiman

    2016-01-01

    Full Text Available Background: Most of the herbal medicines in the world originate from the developing countries. There are ample opportunities for these countries to expand their global export. The world market for botanical medicines including drug products and raw materials has been estimated to have an annual growth rate between 5% and 15%. Total global botanical drug market is estimated at US$62 billion and is expected to grow to the tune of US$5 trillion by the year 2050. In the USA alone, the usage of botanicals has been increased by 380% between the years 1990 and 1997. Materials and Methods: Ayurveda, the Indian system of medicine, is one of the ancient, yet living traditions that face a typical Western bias. Widespread and growing use of botanicals has created public health challenges globally in terms of quality, safety, and efficacy. Results and Discussion: The development of parameters for standardization and quality control of botanicals is a challenging task. Various regulatory authorities, research organizations, and botanical drug manufacturers have contributed in developing guiding principles and addressing issues related to the quality, safety, and efficacy. Conclusions: The present review describes the regulatory aspects of herbal drugs in India and various other countries.

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

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    Mar Pujades-Rodríguez

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

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    Filippo Montemurro

    2010-09-01

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

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

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    Kumarasamy Nagalingeswaran

    2010-03-01

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

  3. Development of a Standardized Rating Tool for Drug Alerts to Reduce Information Overload.

    Science.gov (United States)

    Pfistermeister, Barbara; Sedlmayr, Brita; Patapovas, Andrius; Suttner, Gerald; Tektas, Ozan; Tarkhov, Aleksey; Kornhuber, Johannes; Fromm, Martin F; Bürkle, Thomas; Prokosch, Hans-Ulrich; Maas, Renke

    2016-12-07

    A well-known problem in current clinical decision support systems (CDSS) is the high number of alerts, which are often medically incorrect or irrelevant. This may lead to the so-called alert fatigue, an overriding of alerts, including those that are clinically relevant, and underuse of CDSS in general. The aim of our study was to develop and to apply a standardized tool that allows its users to evaluate the quality of system-generated drug alerts. The users' ratings can subsequently be used to derive recommendations for developing a filter function to reduce irrelevant alerts. We developed a rating tool for drug alerts and performed a web-based evaluation study that also included a user review of alerts. In this study the following categories were evaluated: "data linked correctly", "medically correct", "action required", "medication change", "critical alert", "information gained" and "show again". For this purpose, 20 anonymized clinical cases were randomly selected and displayed in our customized CDSS research prototype, which used the summary of product characteristics (SPC) for alert generation. All the alerts that were provided were evaluated by 13 physicians. The users' ratings were used to derive a filtering algorithm to reduce overalerting. In total, our CDSS research prototype generated 399 alerts. In 98 % of all alerts, medication data were rated as linked correctly to drug information; in 93 %, the alerts were assessed as "medically correct"; 19.5 % of all alerts were rated as "show again". The interrater-agreement was, on average, 68.4 %. After the application of our filtering algorithm, the rate of alerts that should be shown again decreased to 14.8 %. The new standardized rating tool supports a standardized feedback of user-perceived clinical relevance of CDSS alerts. Overall, the results indicated that physicians may consider the majority of alerts formally correct but clinically irrelevant and override them. Filtering may help to reduce

  4. Approaches to Increasing Ethical Compliance in China with Drug Trial Standards of Practice

    DEFF Research Database (Denmark)

    Rosenberg, Jacob

    2016-01-01

    . With recent reports of scientific misconduct from China, there is an urgent need to find approaches to compel researchers to adhere to ethical research practices. This problem does not call for a simple solution, but if forces are joined with governmental regulations, education in ethics issues for medical...... researchers, and strong reinforcement by Chinese journal editors not to publish studies with these flaws, then research ethics and publication standards will probably improve. Other solutions to foster ethical practice of drug trials are discussed including Chinese initiatives directed at managing conflict...... of interest from the pharmaceutical industry and educating clinical researchers....

  5. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia.

    Science.gov (United States)

    Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Levato, Luciano; D'Adda, Mariella; Stagno, Fabio; Tiribelli, Mario; Salvucci, Marzia; Fava, Carmen; Martino, Bruno; Cedrone, Michele; Bocchia, Monica; Trabacchi, Elena; Cavazzini, Francesco; Usala, Emilio; Russo Rossi, Antonella; Bochicchio, Maria Teresa; Soverini, Simona; Alimena, Giuliana; Cavo, Michele; Pane, Fabrizio; Martinelli, Giovanni; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

    2015-09-01

    Nilotinib is a second-generation tyrosine kinase inhibitor that has been approved for the first-line treatment of chronic-phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib versus imatinib (ENESTnd). Apart from this registration study, very few data are currently available on first-line nilotinib treatment. We report here the long-term, 6-year results of the first investigator-sponsored, GIMEMA multicenter phase 2, single-arm trial with nilotinib 400 mg twice daily as first-line treatment in 73 patients with chronic-phase chronic myeloid leukemia. Six-year overall survival and progression-free survival rates were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose of nilotinib (400 mg twice daily): it highlights the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). Copyright© Ferrata Storti Foundation.

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  8. Effects of moderate beer consumption on first-line immunity of healthy adults.

    Science.gov (United States)

    Romeo, J; Wärnberg, J; Díaz, L E; González-Gross, M; Marcos, A

    2007-06-01

    Moderate alcohol consumption has shown to induce benefits on host specific (cell-mediated and humoral) immune system, but there is scarce literature regarding first-line immune responses. The aim of this study was to investigate differences in non-specific immunity after alcohol abstention and moderate beer consumption in healthy adults. After a 30 day-alcohol abstemious period, 57 healthy volunteers were submitted to a daily moderate consumption of beer (330 mL for women and 660 mL for men, respectively) during the following 30 days. White blood cell counts and phagocytic and oxidative burst activity were evaluated at three points: a) basal, b) abstemious, c) after moderate consumption of beer. Absolute values of leukocytes, neutrophils, lymphocytes and basophiles (x10(9)/L) increased significantly in women from point b to point c (6.34 +/- 1.26 vs. 7.27 +/- 1.97, 3.43 +/- 0.88 vs. 4.13 +/- 1.53, 2.14 +/- 0.50 vs. 2.38 +/- 0.63, and 0.05 +/- 0.02 vs. 0.06 +/- 0.03, respectively; p consumption of beer in both women (33.90 +/- 19.00 vs. 48.86 +/- 21.83) and men (27.39 +/- 18.13 vs. 39.25 +/- 24.53). In healthy adults, after 30 days of moderate beer consumption the parameter describing the non-specific immunity improved when compared to the basal situation. For several of these parameters, the response is more enhanced in women.

  9. Partial Adrenalectomy: An Underutilized First Line Therapy for Small Adrenal Tumors

    Science.gov (United States)

    Kaye, Deborah R.; Storey, Benjamin B.; Pacak, Karel; Pinto, Peter A.; Linehan, W. Marston; Bratslavsky, Gennady

    2011-01-01

    Purpose Many patients with small adrenal masses undergo total adrenalectomy. We evaluate the outcomes of partial adrenalectomy by performing a comprehensive literature review. Materials and Methods We performed a Pubmed search of literature published in the English language using the following queries: “partial adrenalectomy” and “adrenal sparing surgery”, and identified 317 and 155 articles, respectively. We excluded case reports or series containing less than 5 patients, articles not focused on surgical management, and those that did not indicate perioperative outcomes. The remaining articles were cross-referenced by author and institution in order to eliminate studies with redundant cases. Demographics, diagnosis, tumor characteristics, perioperative and functional outcomes, as well as recurrence data was collected when available. Results Twenty-two articles from 22 first authors met our inclusion criteria describing outcomes of 417 patients. There is an increasing trend towards utilization of partial adrenalectomy worldwide over the past 20 years. Partial adrenalectomy is most commonly performed for Conn's Syndrome, followed by pheochromocytoma. Most of the procedures are performed laparoscopically with minimal morbidity. The recurrence rate is only at 3% and over 90% of patients remain steroid independent. Conclusions Surgical outcomes and perioperative complications of partial adrenalectomy are similar to those reported for total adrenalectomy. When partial adrenalectomy is performed for small adrenal lesions, the rate of malignancy is negligible, the recurrence rate is low, and the vast majority of patients remain steroid independent at long-term follow up. These data strongly support acceptance of partial adrenalectomy as a first line treatment for small adrenal masses. PMID:20546805

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

    Science.gov (United States)

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

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

  11. First-line chemotherapy in low-risk gestational trophoblastic neoplasia

    Science.gov (United States)

    Alazzam, Mo’iad; Tidy, John; Hancock, Barry W; Osborne, Raymond; Lawrie, Theresa A

    2014-01-01

    Background This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. Objectives To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN. Search methods In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review. Selection criteria For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs. Data collection and analysis Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials. Main results We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women). Overall, dactinomycin was associated

  12. [Standardize the endovascular treatment for arteriosclerosis obliterans].

    Science.gov (United States)

    Wang, S M; Yao, C

    2016-08-01

    Endovascular therapy has become the first-line strategy for most peripheral artery disease cases. Currently, many guidelines recommend endovascular therapy as the first choice for arteriosclerosis obliterans. Recently, drug-eluting stent and drug-coated balloon are available. The clinical outcomes have been greatly improved with the evolution of devices. However, the long-term outcomes of endovascular therapy for arteriosclerosis obliterans are still not satisfied. Many centers treat arteriosclerosis obliterans using endovascular therapy in appropriately. In this editorial, an evidence-based approach and some strategies will be discussed to standardize the endovascular treatment and improve the result of endovascular therapy for arteriosclerosis obliterans.

  13. Scandinavian SSAI clinical practice guideline on choice of first-line vasopressor for patients with acute circulatory failure.

    Science.gov (United States)

    Møller, M H; Claudius, C; Junttila, E; Haney, M; Oscarsson-Tibblin, A; Haavind, A; Perner, A

    2016-11-01

    Adult critically ill patients often suffer from acute circulatory failure, necessitating use of vasopressor therapy. The aim of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force for Acute Circulatory Failure was to present clinically relevant, evidence-based treatment recommendations on this topic. This guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations. We assessed the following subpopulations of patients with acute circulatory failure: 1) shock in general, 2) septic shock, 3) cardiogenic shock, 4) hypovolemic shock and 5) other types of shock, including vasodilatory shock. We assessed patient-important outcome measures, including mortality, serious adverse reactions and quality-of-life. For patients with shock in general and those with septic shock, we recommend using norepinephrine rather than dopamine, and we suggest using norepinephrine rather than epinephrine, vasopressin analogues, and phenylephrine. For patients with cardiogenic shock and those with hypovolemic shock, we suggest using norepinephrine rather than dopamine, and we provide no recommendations/suggestions of norepinephrine vs. epinephrine, vasopressin analogues, and phenylephrine. For patients with other types of shock, including vasodilatory shock, we suggest using norepinephrine rather than dopamine, epinephrine, vasopressin analogues, and phenylephrine. We recommend using norepinephrine rather than other vasopressors as first-line treatment for the majority of adult critically ill patients with acute circulatory failure. © 2016 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

  14. First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors.

    Science.gov (United States)

    Vivaldi, Caterina; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Catanese, Silvia; Fornaro, Lorenzo; Lencioni, Monica; Falcone, Alfredo; Vasile, Enrico

    2016-08-15

    FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated efficacy in metastatic colorectal cancer. We aimed to evaluate activity and tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative prognostic factors. One hundred thirty-seven consecutive aPC patients were treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical, laboratory and pathological data were collected and their association with activity, progression free survival (PFS) and overall survival (OS) was investigated. After a median follow up of 30 months, median PFS and OS were 8.0 months (95% CI 6.19-9.81) and 12 months (95% CI 9.75-14.25), respectively. Response rate was 38.6%, while disease-control rate 72.2%. At multivariate analysis liver metastases (p = 0.019; Hazard Ratio, HR, 0.59, 95% Confidence Interval, CI, 0.380.96), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 (p = 0.001; HR 2.26, 95%CI 1.42-3.59) and neutrophil-lymphocyte ratio (NLR)> 4 (p= 0.002; HR: 2.42; 95% CI 1.38-4.25) were associated with poorer OS. We categorized 119 pts with complete available data as good-risk (0 factors, 38 pts), intermediate-risk (1 factor, 49 pts) and poor-risk (≥2 factors, 32 pts). Median OS for these three groups were 17.6, 11.1 and 7.4 months, respectively (p < 0.001). FOLFOXIRI is active and feasible in aPC. Prognosis of aPC pts treated with FOLFOXIRI is influenced by easily available factors: our analysis revealed ECOG PS, liver metastases and NLR as the most important predictors of survival. These factors could be helpful for treatment decision and clinical trial design. © 2016 UICC.

  15. Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in chronic phase: a phase 2 study.

    Science.gov (United States)

    Jain, Preetesh; Kantarjian, Hagop; Jabbour, Elias; Gonzalez, Graciela Nogueras; Borthakur, Gautam; Pemmaraju, Naveen; Daver, Naval; Gachimova, Evguenia; Ferrajoli, Alessandra; Kornblau, Steven; Ravandi, Farhad; O'Brien, Susan; Cortes, Jorge

    2015-09-01

    Ponatinib has shown efficacy in patients with refractory chronic myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed to investigate the activity and safety of ponatinib as first-line treatment for patients with chronic-phase CML. We did a single-arm, phase 2 trial at MD Anderson Cancer Center in Houston, TX, USA. Between May 3, 2012, and Sept 24, 2013, we enrolled patients with early (<6 months) chronic-phase CML and treated them with oral ponatinib once a day. Patients enrolled before July 25, 2013, were given a starting dose of 45 mg per day; we lowered this due to tolerability issues and patients enrolled after this date were given a starting dose of 30 mg per day. After a warning by the US Food and Drug Administration (FDA) in Oct 6, 2013, for vascular complications with ponatinib, we started all patients on aspirin 81 mg daily and reduced the dose of ponatinib to 30 mg or 15 mg per day for all patients. The primary endpoint was the proportion of patients who achieved complete cytogenetic response by 6 months in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01570868. We enrolled 51 patients. Median follow-up was 20·9 months (IQR 14·9–25·2). 43 patients were started on 45 mg ponatinib every day; eight patients were started on 30 mg per day. 43 (94%) of 46 evaluable patients achieved complete cytogenetic response at 6 months. Most frequent toxicities included skin-related effects (n=35; 69%) and elevated lipase (n=32; 63%). Cardiovascular events (mainly hypertension) occurred in 25 (49%) patients. Grade 3–4 myelosuppression occurred in 15 (29%) patients. Five (10%) patients developed cerebrovascular or vaso-occlusive disease. 43 (85%) patients needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated June 18, 2014, at the recommendation of the FDA due to concern about the increased risk of thromboembolism with ponatinib. Patients with

  16. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    Science.gov (United States)

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-08-01

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

  18. Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

    Science.gov (United States)

    Fornaro, Lorenzo; Vivaldi, Caterina; Cereda, Stefano; Leone, Francesco; Aprile, Giuseppe; Lonardi, Sara; Silvestris, Nicola; Santini, Daniele; Milella, Michele; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Falcone, Alfredo; Brandi, Giovanni; Sperduti, Isabella; Vasile, Enrico

    2015-12-23

    After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

  19. Non-Cross Resistant Sequential Single Agent Chemotherapy in First-Line Advanced Non-Small Cell Lung Cancer Patients: Results of a Phase II Study

    Directory of Open Access Journals (Sweden)

    V. Surmont

    2009-01-01

    Full Text Available Background. sequential chemotherapy can maintain dose intensity and preclude cumulative toxicity by increasing drug diversity. Purpose. to investigate the toxicity and efficacy of the sequential regimen of gemcitabine followed by paclitaxel in first line advanced stage non-small cell lung cancer (NSCLC patients with good performance status (PS. Patients and methods. gemcitabine 1250 mg/m2 was administered on day 1 and 8 of course 1 and 2; Paclitaxel 150 mg/m2 on day 1 and 8 of course 3 and 4. Primary endpoint was response rate (RR, secondary endpoints toxicity and time to progression (TTP. Results. Of the 21 patients (median age 56, range 38–80 years; 62% males, 38% females 10% (2/21 had stage IIIB, 90% (19/21 stage IV, 15% PS 0, 85% PS 1. 20% of patients had a partial response, 30% stable disease, 50% progressive disease. Median TTP was 12 weeks (range 6–52 weeks, median overall survival (OS 8 months (range 1–27 months, 1-year survival was 33%. One patient had grade 3 hematological toxicity, 2 patients a grade 3 peripheral neuropathy. Conclusions. sequential administration of gemcitabine followed by paclitaxel in first line treatment of advanced NSCLC had a favourable toxicity profile, a median TTP and OS comparable with other sequential trials and might , therefore, be a treatment option for NSCLC patients with high ERCC1 expression.

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

    DEFF Research Database (Denmark)

    Mocroft, A; Reiss, P; Rakhmanova, A

    2014-01-01

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

  1. Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial.

    Science.gov (United States)

    Hancock, Mark J; Maher, Chris G; Latimer, Jane; McLachlan, Andrew J; Cooper, Chris W; Day, Richard O; Spindler, Megan F; McAuley, James H

    2007-11-10

    We aimed to investigate whether the addition of non-steroidal anti-inflammatory drugs or spinal manipulative therapy, or both, would result in faster recovery for patients with acute low back pain receiving recommended first-line care. 240 patients with acute low back pain who had seen their general practitioner and had been given advice and paracetamol were randomly allocated to one of four groups in our community-based study: diclofenac 50 mg twice daily and placebo manipulative therapy (n=60); spinal manipulative therapy and placebo drug (n=60); diclofenac 50 mg twice daily and spinal manipulative therapy (n=60); or double placebo (n=60). The primary outcome was days to recovery from pain assessed by survival curves (log-rank test) in an intention-to-treat analysis. This trial was registered with the Australian Clinical Trials Registry, ACTRN012605000036617. Neither diclofenac nor spinal manipulative therapy appreciably reduced the number of days until recovery compared with placebo drug or placebo manipulative therapy (diclofenac hazard ratio 1.09, 95% CI 0.84-1.42, p=0.516; spinal manipulative therapy hazard ratio 1.01, 95% CI 0.77-1.31, p=0.955). 237 patients (99%) either recovered or were censored 12 weeks after randomisation. 22 patients had possible adverse reactions including gastrointestinal disturbances, dizziness, and heart palpitations. Half of these patients were in the active diclofenac group, the other half were taking placebo. One patient taking active diclofenac had a suspected hypersensitivity reaction and ceased treatment. Patients with acute low back pain receiving recommended first-line care do not recover more quickly with the addition of diclofenac or spinal manipulative therapy.

  2. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

    Science.gov (United States)

    Hortobagyi, Gabriel N; Stemmer, Salomon M; Burris, Howard A; Yap, Yoon-Sim; Sonke, Gabe S; Paluch-Shimon, Shani; Campone, Mario; Blackwell, Kimberly L; André, Fabrice; Winer, Eric P; Janni, Wolfgang; Verma, Sunil; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Petrakova, Katarina; Hart, Lowell L; Villanueva, Cristian; Chan, Arlene; Jakobsen, Erik; Nusch, Arnd; Burdaeva, Olga; Grischke, Eva-Maria; Alba, Emilio; Wist, Erik; Marschner, Norbert; Favret, Anne M; Yardley, Denise; Bachelot, Thomas; Tseng, Ling-Ming; Blau, Sibel; Xuan, Fengjuan; Souami, Farida; Miller, Michelle; Germa, Caroline; Hirawat, Samit; O'Shaughnessy, Joyce

    2016-11-03

    The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10-5. The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10-6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2

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

    Science.gov (United States)

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

    2016-10-11

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

  5. Should progressive perineal dilation be considered first line therapy for vaginal agenesis?

    Science.gov (United States)

    Gargollo, Patricio C; Cannon, Glenn M; Diamond, David A; Thomas, Phaedra; Burke, Vicki; Laufer, Marc R

    2009-10-01

    ) dilation and the initiation of sexual activity. Complications were minor. Three patients reported infrequent pain and 2 reported a single episode of bleeding with dilation. A total of 18 sexually active patients reported satisfactory intercourse without dyspareunia. Progressive perineal dilation for neovaginal creation is a valuable, minimally invasive therapy to create a functional vagina with a high success rate and a much lower complication rate than that in published surgical series. Given these findings, progressive perineal dilation should be offered as first line therapy in adolescents with a congenitally absent vagina.

  6. Resistance to first-line anti-TB drugs is associated with reduced nitric oxide susceptibility in Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Idh, Jonna; Mekonnen, Mekidim; Abate, Ebba

    2012-01-01

    The relative contribution of nitric oxide (NO) to the killing of Mycobacterium tuberculosis in human tuberculosis (TB) is controversial, although this has been firmly established in rodents. Studies have demonstrated that clinical strains of M. tuberculosis differ in susceptibility to NO, but how...

  7. Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial.

    Science.gov (United States)

    Masi, G; Salvatore, L; Boni, L; Loupakis, F; Cremolini, C; Fornaro, L; Schirripa, M; Cupini, S; Barbara, C; Safina, V; Granetto, C; Fea, E; Antonuzzo, L; Boni, C; Allegrini, G; Chiara, S; Amoroso, D; Bonetti, A; Falcone, A

    2015-04-01

    The combination of bevacizumab with fluorouracil-based chemotherapy is a standard first-line treatment option in metastatic colorectal cancer (mCRC). We studied the efficacy of continuing or reintroducing bevacizumab in combination with second-line chemotherapy after progression to bevacizumab-based first-line therapy. In this phase III study, patients with mCRC treated with fluoropyrimidine-based first-line chemotherapy plus bevacizumab were randomized to receive in second-line mFOLFOX-6 or FOLFIRI (depending on first-line regimen) with or without bevacizumab. The primary end point was progression-free survival. To detect a hazard ratio (HR) for progression of 0.70 with an α and β error of 0.05 and 0.20, respectively, 262 patients were required. In consideration of the results of the ML18147 trial, the study was prematurely stopped. Between April 2008 and May 2012, a total of 185 patients were randomized. Bevacizumab-free interval was longer than 3 months in 43% of patients in chemotherapy alone arm and in 50% of patients in the bevacizumab arm. At a median follow-up of 45.3 months, the median progression-free survival was 5.0 months in the chemotherapy group and 6.8 months in the bevacizumab group [adjusted HR = 0.70; 95% confidence interval (CI) 0.52-0.95; stratified log-rank P = 0.010]. Subgroup analyses showed a consistent benefit in all subgroups analyzed and in particular in patients who had continued or reintroduced bevacizumab. An improved overall survival was also observed in the bevacizumab arm (adjusted HR = 0.77; 95% CI 0.56-1.06; stratified log-rank P = 0.043). Responses (RECIST 1.0) were similar in the chemotherapy and bevacizumab groups (17% and 21%; P = 0.573). Toxicity profile was consistent with previously reported data. This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of m

  8. Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual Patient-Level Analysis of Multiple Randomized Trials.

    Science.gov (United States)

    Shi, Qian; Flowers, Christopher R; Hiddemann, Wolfgang; Marcus, Robert; Herold, Michael; Hagenbeek, Anton; Kimby, Eva; Hochster, Howard; Vitolo, Umberto; Peterson, Bruce A; Gyan, Emmanuel; Ghielmini, Michele; Nielsen, Tina; De Bedout, Sabine; Fu, Tommy; Valente, Nancy; Fowler, Nathan H; Hoster, Eva; Ladetto, Marco; Morschhauser, Franck; Zucca, Emanuele; Salles, Gilles; Sargent, Daniel J

    2017-02-10

    Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to formally assess the complete response rate at 30 months (CR30) after initiation of induction therapy as a potential surrogate end point for PFS in first-line FL therapy. Patients and Methods We analyzed individual patient data from 13 randomized multicenter trials of induction and maintenance regimens in first-line FL therapy published after 1990 and with sufficient data to evaluate whether CR30 could predict treatment effects on PFS. Correlation of the CR30 odds ratio with the PFS hazard ratio was evaluated by both linear regression (R2WLS) and bivariate copula (R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80, with a lower-bound 95% CI > 0.60. Results Data from eight induction and five maintenance randomized trials in 3,837 evaluable patients were analyzed. The prespecified surrogacy threshold was met, with an R2WLS of 0.88 (95% CI, 0.77 to 0.96) and an R2Copula of 0.86 (95% CI, 0.72 to 1.00). Multiple sensitivity and supplemental analyses supported the robustness of the findings. A minimum 11% absolute improvement in CR30 from a 50% control rate predicted a significant treatment effect on PFS (hazard ratio, 0.69). Conclusion This large, prospective, pooled analysis of randomized chemotherapy, immunotherapy, and chemoimmunotherapy trials demonstrates that CR30 is a surrogate end point for PFS in first-line FL treatment trials. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before PFS results are mature.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0.97-2.62, P = 0...

  13. The sensitivities to first-line antibiotic therapy of the common urinary ...

    African Journals Online (AJOL)

    Background: Urinary tract infections (UTIs) are among the most common human infections. Many urinary tract bacteria are capable of expressing drug resistance. Resistant bacteria may be present from the commencement of the infection or may develop during treatment. This study focused on the problem of antibiotic ...

  14. The sensitivities to first-line antibiotic therapy of the common urinary ...

    African Journals Online (AJOL)

    Unlike the Staphylococcus species that were significantly resistant to nitrofurantoin, Streptococcus species were moderately susceptible to the drug. Conclusion: The common urinary tract bacteria detected in Rubaga hospital in Uganda were most sensitive to Ciprofloxacin and Nitrofurantoin. African Health Sciences Vol.

  15. Trial efficacy vs real world effectiveness in first line treatment of multiple myeloma

    NARCIS (Netherlands)

    Liwing, J.; Heeg, B.M.; Karstorp, S.; Postma, M.; Silvennoinen, R.; Putkonen, M.; Anttila, P.; Remes, K.; Abildgaard, N.; Waage, A.; Nahi, H.

    2015-01-01

    Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to

  16. A Randomized Trial of Liposomal Paclitaxel plus Cisplatin as First-line Therapy for Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xi LI

    2012-04-01

    Full Text Available Background and objective Paclitaxel plus cisplatin (TP is used as the standard regimen for patients with advanced non-small cell lung cancer (NSCLC. In this study, we compared the response rate (RR, overall survival (OS, and toxicity of the combined chemotherapy regimen of liposomal paclitaxel plus cisplatin (LP with those of TP as first-line treatments for advanced NSCLC. Methods A total of 100 patients were randomly selected to be treated with liposomal paclitaxel or paclitaxel at a dose of 150 mg/m2 on day 1 plus cisplatin at a dose of 75 mg/m2 on days 1 and 2 per cycle every 21 days. Results All 100 patients were eligible. The median progression free survival was 5.1 months vs 4.2 months, the median OS was 9.0 months vs 9.3 months, and RR was 26% vs 24% in the LP and TP arms, respectively. No significant difference was observed (P=0.110, 0.342 and 0.890, respectively. There was no significant difference between grades 3 and 4 toxicity of the arms (P>0.05. Peripheral neuritis observed in the LP arm was significantly lower than that in the TP arm (8% vs 28%, and the difference was statistically significant (P=0.030. Conclusion The effects of LP and TP as first-line therapies for NSCLC are similar. However, peripheral neuritis in the LP arm is significantly lower than in the TP arm.

  17. 78 FR 6762 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-01-31

    ...The Food and Drug Administration (FDA) is announcing a public meeting to discuss the proposed rules to establish standards for the growing, harvesting, packing, and holding of produce for human consumption (the produce safety proposed rule) and for current good manufacturing practice and hazard analysis and risk-based preventive controls for human food (the preventive controls proposed rule), which are the first of several proposed rules that would establish the foundation of, and central framework for, the modern food safety system envisioned by Congress in the FDA Food Safety Modernization Act (FSMA). The purpose of the public meeting is to solicit oral stakeholder and public comments on the proposed rules and to inform the public about the rulemaking process (including how to submit comments, data, and other information to the rulemaking dockets), and to respond to questions about the proposed rules.

  18. [Pefloxacin as a first-line treatment for nephrotic syndrome in minimal glomerular lesions in the adult. Multicenter study of 32 patients].

    Science.gov (United States)

    Pruna, A; Barka, A; Nochy, D; Hauet, T; Boulanger, H; Landais, P

    1997-01-01

    Minimal change nephrotic syndrome (MCNS) is the most frequent single cause of nephrotic syndrome occurring both in adults and children. Although it appears to be a self-limiting disorder (10% spontaneous remissions within the fortnight following the initial flare), MCNS displays a high rate of complications during the nephrotic period (10 to 15% cases) and prompts one to treat patients as early as possible. Corticosteroids are currently used as first-line treatment. A 16 weeks full-dose steroid course (1 mg/kg/day) usually induces remission in 75% MCNS in adults. Nevertheless, duration of treatment (9 months) and occurrence of relapses despite a slowly tapering dosage schedule, expose patients to steroids side-effects. Immunosuppressive drugs are recommended in case of steroid resistance and their side-effects are not harmless. Therefore, an alternative to steroids or immunosuppressives would lend a serious helping hand in MCNS management. The present work is dealing with pefloxacin efficacy in 40% MCNS in adults. Thirty-two MCNS adult patients were treated in a national multicenter study. A short-duration pefloxacin course (4 to 6 weeks) allowed partial or complete remission in 13 out of 32 cases. Thus far, this effect was undescribed for this class of drugs. Pefloxacin belongs to antibacterial agents of the fluoroquinolone family and is active against Gram negative Enterobacteria species. Fluoroquinolones also act on eukaryotic cells as lymphocytes and chondrocytes and alter IL2, gamma IFN and integrin expression. Although their precise mode of action is unknown in this kind of immunological disorder, fluoroquinolones might represent an alternative to steroids in some adult form of MCNS. However, predictive criteria for sensitivity to fluoroquinolones are currently not available and further controlled studies would be helpful using fluoroquinolones as first-line treatment in all the MCNS.

  19. Designing and screening of universal drug from neem (Azadirachta indica) and standard drug chemicals against influenza virus nucleoprotein.

    Science.gov (United States)

    Ahmad, Aftab; Javed, Muhammad Rizwan; Rao, Abdul Qayyum; Husnain, Tayyab

    2016-12-16

    Different strains of influenza virus are affecting a large number of people worldwide. Many synthetic antiviral medicines are available for influenza virus in the market. But still there is a need for the development of universal drugs against these strains of influenza virus. For this purpose conserved residues within the influenza virus nucleoprotein have been retrieved. The drugs, previously known to have antiviral properties, were screened to identify the best candidate universal drug against Influenza virus strains. Compounds from leaf extracts of neem, were also screened to identify the natural drugs without side effects. Molecular docking identified three potential compounds (Nimbaflavone, Rutin, and Hyperoside) having perfect binding with reported conserved residues (ASP302, SER50) of influenza virus nucleoprotein that is involved in the binding of drugs. Further analysis showed Hyperoside as a universal drug against various influenza strains. Some chemical drugs were also evaluated through screening against nucleoprotein. The results showed six drugs (OMS, CBX, LGH, Naproxen, BMS-883559, and BMS-885838) which were interacting with same conserved residues (ASP302, TYR52, SER50, GLY288, SER376, and ARG99) as were found in the case of neem phytochemicals. Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein. The compound Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein. So these compounds have been identified for their potential against influenza strains to be utilized as a universal drug.

  20. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    .... Background The globalization of the pharmaceutical market has created tremendous challenges for FDA... government? 8. Should FDA require that importers submit certificates of analysis (COAs) to the Agency as a..., drugs for further processing, active pharmaceutical ingredients, and other drug components, including...

  1. A computerized standard protocol order entry for pediatric inpatient acute seizure emergencies reduces time to treatment.

    Science.gov (United States)

    Xie, Yi; Morgan, Robin; Schiff, Linda; Hannah, Debbie; Wheless, James

    2014-02-01

    Time to treatment of seizures is critical to efficacy. We performed a quality initiative and evaluated time to treatment of inpatient seizure emergencies with first- and second-line medicines before and after implementation of a computerized, standard treatment protocol. Data from 125 patients revealed that 179 seizure episodes required first-line antiepileptic drugs, and the mean time to treatment was 7.72 minutes. In 87 episodes, patients (49%) received the drugs within 5 minutes. Forty-six episodes required second-line drugs. In 17 (37%), patients received them within 30 minutes (mean 49.48 minutes). After implementation of the protocol, the mean time to treatment with first-line drugs was 3.74 minutes, a reduction of >50% (P seizure emergencies may be useful to similar institutions.

  2. Correlation between Serum Tumor Markers and Efficacy of First-line EGFR-TKIs in Patients with Advanced Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Hanxiao CHEN

    2017-09-01

    Full Text Available Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs significantly improve the survival of advanced lung adenocarcinoma patients harboring EGFR mutation. Limited to the standards of tumor tissue samples and detection methods, still some people can’t receive target therapy following genetic guidance. This study was to explore the relevance between serum tumor markers and treatment of EGFR-TKIs. Methods We retrospectively collected the clinical information of advanced lung adenocarcinoma patients harboring EGFR mutation, who received EGFR-TKIs as first-line therapy from June 2009 to June 2014 in Peking University Cancer Hospital, analyzed the relationship between serum tumor markers and efficacy of EGFR-TKIs. Results The objective response rate (ORR was 52.8% and the disease control rate (DCR was 89.3%. The results showed that, patients with high CEA level before treatment responded better to TKIs (ORR 61.3% vs 35.9%, DCR 95.2% vs 74.4%, P<0.001. Similar phenomena was found in patients with CEA decreased 1 month later (61.5% vs 25%, P=0.002. Progression-free survival (PFS significantly prolonged in patients with elevated baseline CEA (mPFS 9.8 mo vs 5.9 mo, P=0.027. To the opposite, PFS was significantly shorter in patients with elevated baseline CYFRA21-1 and CA125 (mPFS 9.0 mo vs 11.4 mo, P=0.029; 9.0 mo vs 11.5 mo, P=0.023, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG score of 0-1, normal baseline CYFRA21-1 and CEA decline predicted longer PFS. The overall survival (OS was highly associated with elevated CYFRA21-1 and CA125 (median OS 25.1 mo vs 52.5 mo, P=0.003; 22.7 mo vs 55.0 mo, P<0.001, respectively, while independent of CEA. Conclusion High level of baseline CEA and decline 1 month after treatment could predict the efficacy of EGFR-TKIs in patients with advanced lung adenocarcinoma. While high levels of baseline CYFRA21-1 and CA125 indicated shortened

  3. Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Pradines Bruno

    2011-10-01

    Full Text Available Abstract Background As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT (which includes artemether-lumefantrine and artesunate-amodiaquine has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar. Methods The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH ELISA for the following drugs: chloroquine (CQ, quinine (QN, mefloquine (MQ, monodesethylamodiaquine (MDAQ, lumefantrine (LMF, dihydroartemisinin (DHA and doxycycline (DOX. Results After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50, the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P r = 0.511; P r = 0.428; P = 0.0001, LMF and MQ (r = 0.413; P = 0.0002, QN and DHA (r = 0.402; P = 0.0003 and QN and MQ (r = 0.421; P = 0.0001. Conclusions The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.

  4. Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating Epidermal Growth Factor Receptor mutation: implications for clinical practice and open issues.

    Science.gov (United States)

    Gridelli, C; De Marinis, F; Di Maio, M; Cortinovis, D; Cappuzzo, F; Mok, T

    2011-04-01

    Randomized trials comparing gefitinib with chemotherapy as first-line treatment in patients with EGFR mutated advanced NSCLC support gefitinib as a new, highly effective treatment option in this setting. However, its use in clinical practice has several relevant implications and open issues. In order to choose the best treatment, a molecular characterization is now mandatory, as part of baseline diagnostic procedures. Every effort should be made in order to obtain sufficient tissue. If a clinical enrichment has to be performed for selecting patients to test for EGFR mutation, a reasonable proposal is to test all non-squamous tumors, and patients with squamous tumors only if never smokers. In patients with EGFR mutated tumor, one major issue is the decision about immediate use of gefitinib as first-line, or after failure of standard chemotherapy. First-line gefitinib, compared to chemotherapy, is associated with longer progression-free survival, higher response rate, better toxicity profile and quality of life, and its administration as first-line warrants that all patients have the chance of receiving an EGFR inhibitor. Evidence about the efficacy of erlotinib in the same setting will be soon available, however, at the moment, there are no direct comparisons between gefitinib and erlotinib in EGFR mutated patients. Treatment with gefitinib is usually well tolerated. Typical side effects in most cases are of mild to moderate intensity, and usually manageable with temporary interruption of treatment. When indicated gefitinib appears feasible also in special populations, like elderly or unfit patients, characterized by a significantly poorer risk/benefit ratio with standard chemotherapy. Personalized medicine for patients with lung cancer is now a reality, and patients with EGFR mutation should be treated with first-line EGFR tyrosine kinase inhibitor. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

    NARCIS (Netherlands)

    S.Y. Rhee (Soo Yoon); J.L. Blanco (Jose Luis); M.R. Jordan (Michael); J. Taylor (Jonathan); P. Lemey (Philippe); V. Varghese (Vici); R.L. Hamers (Raph); S. Bertagnolio (Silvia); M. De Wit (Meike); A.F. Aghokeng (Avelin); J. Albert (Jan); R. Avi (Radko); S. Avila-Rios (Santiago); P.O. Bessong (Pascal O.); J.I. Brooks (James I.); C.A. Boucher (Charles); Z.L. Brumme (Zabrina L.); M.P. Busch (Michael P.); H. Bussmann (Hermann); M.L. Chaix (Marie Laure); B.S. Chin (Bum Sik); T.T. D’Aquin (Toni T.); C. de Gascun (Cillian); A. Derache (Anne); D. Descamps (Diane); A.K. Deshpande (Alaka K.); C.F. Djoko (Cyrille F.); S.H. Eshleman (Susan H.); H. Fleury (Hervé); P. Frange (Pierre); S. Fujisaki (Seiichiro); P. Harrigan (Pr); J. Hattori (Junko); A. Holguin (Africa); G.M. Hunt (Gillian M.); H. Ichimura (Hiroshi); P. Kaleebu (Pontiano); D. Katzenstein (David); S. Kiertiburanakul (Sasisopin); J.H. Kim (Jerome H.); S.S. Kim (Sung Soon); Y. Li (Yanpeng); I. Lutsar (Irja); L. Morris (L.); N. Ndembi (Nicaise); K.P. NG (Kee Peng); R.S. Paranjape (Ramesh S.); M.C. Peeters (Marian); M. Poljak (Mario); M.A. Price (Matt A.); M.L. Ragonnet-Cronin (Manon L.); G. Reyes-Terán (Gustavo); M. Rolland (Morgane); S. Sirivichayakul (Sunee); D.M. Smith (Davey M.); M.A. Soares (Marcelo A.); V. Soriano (Virtudes); D. Ssemwanga (Deogratius); M. Stanojevic (Maja); M.A. Stefani (Mariane A.); W. Sugiura (Wataru); S. Sungkanuparph (Somnuek); A. Tanuri (Amilcar); K.K. Tee (Kok Keng); H.-H.M. Truong (Hong-Ha M.); D.A.M.C. van de Vijver (David); N. Vidal (Nicole); C. Yang (Chunfu); R. Yang (Rongge); G. Yebra (Gonzalo); J.P.A. Ioannidis (John); A.M. Vandamme (Anne Mieke); R.W. Shafer (Robert)

    2015-01-01

    textabstractRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We

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

    Science.gov (United States)

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

    2017-08-01

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

  7. Final overall survival results and effect of prolonged (≥ 1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial.

    Science.gov (United States)

    Smith, Ian; Pierga, Jean-Yves; Biganzoli, Laura; Cortes-Funes, Hernan; Thomssen, Christoph; Saracchini, Silvana; Nisenbaum, Bella; Pelaez, Ignacio; Duenne, Anja-Alexandra; Pritchard, Kathleen I

    2011-11-01

    The ATHENA study expanded on the safety and efficacy data derived from first-line trials of bevacizumab combined with standard chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC). In ATHENA, 2,264 patients received first-line bevacizumab-containing therapy in routine oncology practice. Overall survival (OS) data are now mature; additional analyses from this large data set can provide insights into treatment duration and the effect of prolonged bevacizumab exposure, where data are currently limited. Patients with HER2-negative LR/mBC received first-line bevacizumab with standard chemotherapy until disease progression, unacceptable toxicity, or physician/patient decision. We performed subgroup analyses on data from patients treated for ≥12 months and those who continued single-agent bevacizumab after stopping chemotherapy. After median follow-up of 20.1 months, median OS was 25.2 months (95% confidence interval [CI] 24.0-26.3 months) in the entire population. Median OS was 30.0 months (95% CI 28.5-32.7 months) in 1,205 patients who continued bevacizumab after discontinuation of chemotherapy and 18.4 months (95% CI 17.2-19.7 months) in 1,058 patients who discontinued bevacizumab before or at the same time as stopping chemotherapy. Bevacizumab treatment was continued for ≥12 months in 473 patients (21%). In most, bevacizumab was administered as monotherapy for extended periods after stopping chemotherapy. In the subgroup of patients treated for ≥12 months, the median time to onset of grade 3-5 adverse events was 5.0 months. There was no evidence that first onset of adverse events of special interest, except for proteinuria, was more common in later than earlier cycles. No relationship was detected between development of hypertension and OS. Findings from these analyses suggest that patients with LR/mBC can receive bevacizumab for prolonged periods without major toxicity or progression of disease. In the absence of progression, continuation of

  8. Optimal First-Line Treatment for Helicobacter pylori Infection: Recent Strategies

    OpenAIRE

    Ju Yup Lee; Kyung Sik Park

    2016-01-01

    A new treatment strategy is needed, as the efficacy of triple therapy containing clarithromycin—the current standard treatment for Helicobacter pylori infection—is declining. Increasing antibiotic resistance of H. pylori is the most significant factor contributing to eradication failure. Thus, selecting the most appropriate regimen depending on resistance is optimal, but identifying resistance to specific antibiotics is clinically challenging. In a region suspected to have high clarithromycin...

  9. Chronic inflammatory demyelinating polyneuropathy in adults: diagnostic approaches and first line therapy

    Directory of Open Access Journals (Sweden)

    N. А. Suponevа

    2016-01-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is among the key reasons of chronic polyneuropathies in adults. Diagnostic algorithm of CIDP in adults is presented. Diagnosis of CIDP is based on clinical and electrodiagnostic criteria of European Federation of Neurological Societies/Peripheral Nervous System in 2010. Principles of CIDP treatment are discussed, including modern trends of standard and 10 % IVIG solutions. 

  10. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro

    OpenAIRE

    Weissenstein, Ulrike; Kunz, Matthias; Urech, Konrad; Baumgartner, Stephan

    2014-01-01

    Background Given the importance of complementary and alternative medicine (CAM) to cancer patients, there is an increasing need to learn more about possible interactions between CAM and anticancer drugs. Mistletoe (Viscum album L.) belongs to the medicinal herbs that are used as supportive care during chemotherapy. In the in vitro study presented here the effect of standardized mistletoe preparations on the cytostatic and cytotoxic activity of several common conventional chemotherapeutic drug...

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

    Science.gov (United States)

    Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima; Gómez-Olivé, Xavier; Rønn, Anita M; Thompson, Ricardo; Alifrangis, Michael

    2008-07-01

    In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the Plasmodium falciparum genes Pfdhfr, Pfdhps and Pfcrt before and a year after the introduction of SP. Samples were collected during two cross sectional surveys in early 2002 and 2003 involving 796 and 692 children one year or older and adults randomly selected living in Maciana, an area located in Manhiça district, Southern Mozambique. Out of these, 171 and 173 P. falciparum positive samples were randomly selected to measure the frequency of resistance- related haplotypes in Pfdhfr, Pfdhps and Pfcrt based on results obtained by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The frequency of the SP-resistance associated Pfdhps double mutant (SGEAA) haplotype increased significantly from 14% to 35% (P drug, Coartem.

  12. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients

    DEFF Research Database (Denmark)

    Wittkop, Linda; Arsandaux, Julie; Trevino, Ana

    2017-01-01

    Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations...... underline the need to identify more potent therapeutic regimens or strategies against HIV-2......., COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were...

  13. Meta-analysis of first-line triple therapy for helicobacter pylori eradication in Korea: is it time to change?

    Science.gov (United States)

    Gong, Eun Jeong; Yun, Sung-Cheol; Jung, Hwoon-Yong; Lim, Hyun; Choi, Kwi-Sook; Ahn, Ji Yong; Lee, Jeong Hoon; Kim, Do Hoon; Choi, Kee Don; Song, Ho June; Lee, Gin Hyug; Kim, Jin-Ho

    2014-05-01

    Proton pump inhibitor (PPI)-based triple therapy consisting of PPI, amoxicillin, and clarithromycin, is the recommended first-line treatment for Helicobacter pylori infection. However, the eradication rate of triple therapy has declined over the past few decades. We analyzed the eradication rate and adverse events of triple therapy to evaluate current practices in Korea. A comprehensive literature search was performed up to August 2013 of 104 relevant studies comprising 42,124 patients. The overall eradication rate was 74.6% (95% confidence interval [CI], 72.1%-77.2%) by intention-to-treat analysis and 82.0% (95% CI, 80.8%-83.2%) by per-protocol analysis. The eradication rate decreased significantly from 1998 to 2013 (P pylori eradication has decreased to an unacceptable level. A novel therapeutic strategy is warranted to improve the effectiveness of first-line treatment for H. pylori infection in Korea.

  14. Noninvasivepositive pressure ventilation vsinvasive mechanical ventilation as first-line therapy for acute hypoxemic respiratory failure in cancer patients.

    Science.gov (United States)

    Rathi, Nisha K; Haque, Sajid A; Nates, Ron; Kosturakis, Alyssa; Wang, Hao; Dong, Wenli; Feng, Lei; Erfe, Rose J; Guajardo, Christina; Withers, Laura; Finch, Clarence; Price, Kristen J; Nates, Joseph L

    2017-06-01

    The objective was to describe the characteristics and outcomes of critically ill cancer patients who received noninvasive positive pressure ventilation (NIPPV) vs invasive mechanical ventilation as first-line therapy for acute hypoxemic respiratory failure. A retrospective cohort study of consecutive adult intensive care unit (ICU) cancer patients who received either conventional invasive mechanical ventilation or NIPPV as first-line therapy for hypoxemic respiratory failure. Of the 1614 patients included, the NIPPV failure group had the greatest hospital length of stay, ICU length of stay, ICU mortality (71.3%), and hospital mortality (79.5%) as compared with the other 2 groups (P ventilation failure is an independent risk factor for ICU mortality, but NIPPV patients who avoided intubation had the best outcomes compared with the other groups. Early vs late intubation did not have a significant impact on outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Clinical Observation of EGFR-TKI as A First-line Therapy on Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jianjie LI

    2012-05-01

    Full Text Available Background and objective It has been proven that epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI significantly benefits advanced non-small cell lung cancer (NSCLC patients harboring EGFR mutations in progression-free survival time with better tolerance. This study is undertaken to analyze efficacy and tolerance of advanced NSCLC patients harboring EGFR mutations taking EGFR-TKI as a first-line therapy. Methods Tumor samples from 54 patients with advanced NSCLC were examined for EGFR activating mutations (deletion mutation in exon 19 and the L858R point mutation in exon 21 by direct sequencing. The patients were first-line treated with oral administration of EGFR-TKI until disease progression. The efficacy and adverse events were observed, and survival was followed up. Results Among the patients, 61% (33 of 54 had EGFR exon 19 deletion, and 39% (21 of 54 had EGFR L858R point mutation. All patients received first-line TKI therapy. The total response rate was 96%, median progression free survival (PFS was 8.3 months and median survival was 19.5 months. The patients with EGFR exon 19 deletion had significantly longer median PFS (9 versus 7 months, P=0.002 and longer median overall survival (OS(25 versus 16 months, P=0.001 than patients with EGFR L858R point mutation. There is no significance in efficacy between gefitinib and erlotinib, and gefitinib is safer than erlotinib. The most common adverse events were rash and diarrhea. Two (4% grade 4 skin toxity effects, two (4% grade 3 aminotransferase level elevations, and one (1 grade 3 stomatitis were observed. Conclusion The first-line EGFR-TKI treatment in advanced NSCLC patients harboring EGFR mutations is efficient and safe, which is more efficient in patients with EGFR exon 19 deletion than those with EGFR L858R mutation.

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

    Science.gov (United States)

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

    2016-10-01

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

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

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    Giroux Leprieur E

    2016-06-01

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

  18. First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype.

    Science.gov (United States)

    Saito, Yoshimasa; Serizawa, Hiroshi; Kato, Yukako; Nakano, Masaru; Nakamura, Masahiko; Saito, Hidetsugu; Suzuki, Hidekazu; Kanai, Takanori

    2015-12-28

    To evaluate the effect of first line esomeprazole (EPZ)-based triple therapy on Helicobacter pylori (H. pylori) eradication. A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or (13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years (male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen (PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry (UMIN000009642). The H. pylori eradication rates by EPZ-based triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors (PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM (P < 0.05). The serum PG I level and PG I/II ratio were significantly increased after eradication of H. pylori (P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZ-based triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other first-generation PPIs in the Japanese population. The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other first-generation PPIs.

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

    Science.gov (United States)

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

    2011-01-01

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

  20. Using standardized methods for research on HIV and injecting drug use in developing/transitional countries: case study from the WHO Drug Injection Study Phase II

    Directory of Open Access Journals (Sweden)

    Stimson Gerry V

    2006-03-01

    Full Text Available Abstract Background Successful cross-national research requires methods that are both standardized across sites and adaptable to local conditions. We report on the development and implementation of the methodology underlying the survey component of the WHO Drug Injection Study Phase II – a multi-site study of risk behavior and HIV seroprevalence among Injecting Drug Users (IDUs. Methods Standardized operational guidelines were developed by the Survey Coordinating Center in collaboration with the WHO Project Officer and participating site Investigators. Throughout the duration of the study, survey implementation at the local level was monitored by the Coordinating Center. Surveys were conducted in 12 different cities. Prior rapid assessment conducted in 10 cities provided insight into local context and guided survey implementation. Where possible, subjects were recruited both from drug abuse treatment centers and via street outreach. While emphasis was on IDUs, non-injectors were also recruited in cities with substantial non-injecting use of injectable drugs. A structured interview and HIV counseling/testing were administered. Results Over 5,000 subjects were recruited. Subjects were recruited from both drug treatment and street outreach in 10 cities. Non-injectors were recruited in nine cities. Prior rapid assessment identified suitable recruitment areas, reduced drug users' distrust of survey staff, and revealed site-specific risk behaviors. Centralized survey coordination facilitated local questionnaire modification within a core structure, standardized data collection protocols, uniform database structure, and cross-site analyses. Major site-specific problems included: questionnaire translation difficulties; locating affordable HIV-testing facilities; recruitment from drug treatment due to limited/selective treatment infrastructure; access to specific sub-groups of drug users in the community, particularly females or higher income groups

  1. Long-term outcome of HER2 positive metastatic breast cancer patients treated with first-line trastuzumab.

    Science.gov (United States)

    Yeo, B; Kotsori, K; Mohammed, K; Walsh, G; Smith, I E

    2015-12-01

    Trastuzumab has changed the natural history of metastatic HER2 positive breast cancer. Some patients remain well and in remission for many years. There is currently no established duration after which trastuzumab in the advanced setting can be safely discontinued. This study aims to evaluate long-term efficacy and cardiac safety of trastuzumab when used as first-line treatment for patients with metastatic HER2 positive breast cancer. We retrospectively identified 215 patients with HER2 positive, locally advanced or metastatic breast cancer who commenced first line trastuzumab-containing therapy for metastatic disease between 2001 and 2010 at The Royal Marsden Hospital. The median progression free survival for all patients was 12 months (95%CI: 10.3-14.6 months); 103 (48%) patients remained in remission beyond one year, 59 (27%) beyond two years and 25 (12%) beyond five years. The median overall survival was 2.6 years (95% confidence interval (CI): 2.2-3.3). The objective response rate (ORR) was 65% with 17 (8%) complete responses and 120 (57%) partial responses. Trastuzumab was well tolerated. Twenty eight (13%) patients recorded any grade of left ventricular dysfunction. There was no significant difference in cardiac toxicity between those patients on less than or more than one year of trastuzumab. Trastuzumab is associated with long-term remissions in a significant proportion of patients with metastatic HER2 positive disease when used in the first-line advanced setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Increased risk of Q151M and K65R mutations in patients failing stavudine-containing first-line antiretroviral therapy in Cambodia.

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    Janin Nouhin

    Full Text Available BACKGROUND: Multi-nucleos(tide resistance (MNR mutations including Q151M, K65R mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region may confer resistance to all molecules of nucleos(tide reverse transcriptase inhibitors (NRTI. The presence of these mutations is an emerging problem compromising non-nucleoside reverse transcriptase inhibitors and protease inhibitors-based therapies. Furthermore, factors associated with selection of these mutations are still not well defined. The current study aimed to evaluate the frequency and to characterize factors associated with the occurrence of multi-nucleos(tide resistance mutations among HIV-1 infected patients failing recommended first-line antiretroviral regimens in Cambodia. METHODOLOGY/PRINCIPAL FINDING: This is a retrospective analysis of HIV-1 drug resistance genotyping of 520 HIV-1 infected patients in virological failure (viral load > 250 copies/mL while on first-line antiretroviral therapy in Cambodia with at least one reverse transcriptase inhibitor resistance associated mutation. Among these 520 patients, a total of 66 subjects (66/520, 12.7% presented ≥ 1 MNR mutation, including Q151M, K65R, and Insert69 for 59 (11.3%, 29 (5.6%, and 2 (0.4% patients, respectively. In multivariate analysis, both Q151M (p = 0.039 and K65R (p = 0.029 mutations were independently associated with current stavudine- compared to zidovudine-use. CONCLUSION: Such selection of mutations by stavudine drastically limits the choice of antiretroviral molecules available for second-line therapy in resource-limited settings. This finding supports the World Health Organization's recommendation for stavudine phase-out.

  3. The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden.

    Science.gov (United States)

    Murphy, Daniel R; Smolen, Lee J; Klein, Timothy M; Klein, Robert W

    2012-10-30

    This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIOP). The study's objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of -3.0. The GIOP cohorts simulated had an initial BMD T-Score of -2.5. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold

  4. An Economic Evaluation of the Posttreatment Prophylactic Effect of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for First-Line Treatment of Plasmodium falciparum Malaria Across Different Transmission Settings in Africa.

    Science.gov (United States)

    Pfeil, Johannes; Borrmann, Steffen; Bassat, Quique; Mulenga, Modest; Talisuna, Ambrose; Tozan, Yesim

    2015-11-01

    Malaria disproportionately affects young children. Clinical trials in African children showed that dihydroartemisinin-piperaquine (DP) is an effective antimalarial and has a longer posttreatment prophylactic (PTP) effect against reinfections than other artemisinin-based combination therapies, including artemether-lumefantrine (AL). Using a previously developed Markov model and individual patient data from a multicenter African drug efficacy trial, we assessed the economic value of the PTP effect of DP versus AL in pediatric malaria patients from health-care provider's perspective in low-to-moderate and moderate-to-high transmission settings under different drug co-payment scenarios. In low-to-moderate transmission settings, first-line treatment with DP was highly cost-effective with an incremental cost-effectiveness ratio of US$5 (95% confidence interval [CI] = -76 to 196) per disability-adjusted life year (DALY) averted. In moderate-to-high transmission settings, DP first-line treatment led to a mean cost saving of US$1.09 (95% CI = -0.88 to 3.85) and averted 0.05 (95% CI = -0.08 to 0.22) DALYs per child per year. Our results suggested that DP might be superior to AL for first-line treatment of uncomplicated childhood malaria across a range of transmission settings in Africa. © The American Society of Tropical Medicine and Hygiene.

  5. Everolimus treatment for patients with autoimmune hepatitis and poor response to standard therapy and drug alternatives in use

    DEFF Research Database (Denmark)

    Ytting, Henriette; Larsen, Fin Stolze

    2015-01-01

    OBJECTIVE: Not all patients with autoimmune hepatitis (AIH) respond to standard medical therapy with corticosteroids and azathioprine. Such patients may develop end-stage liver disease with poor prognosis unless transplantation is considered. Alternatively, the introduction of new therapeutic...... strategies could potentially ameliorate deterioration of liver function. Patients in our tertiary center were selected for everolimus therapy when exhibiting nonresponse or intolerance to combinations of the standard and empirical drugs in use (e.g., mycophenolate mofetil, calcineurin inhibitors [CNIs]). We...

  6. Rabeprazole, Minocycline, Amoxicillin, and Bismuth as First-Line and Second-Line Regimens for Helicobacter pylori Eradication.

    Science.gov (United States)

    Song, Zhiqiang; Suo, Baojun; Zhang, Lingyun; Zhou, Liya

    2016-12-01

    Because of general unavailability of tetracycline, common adverse effects, and complicated administration, the clinical application of bismuth quadruple therapy often faces difficulties. Whether the combination of minocycline and amoxicillin can replace tetracycline and metronidazole for Helicobacter pylori eradication remains unclear. This study was to determine the efficacy, compliance, and safety of rabeprazole, minocycline, amoxicillin, and bismuth (RMAB) therapy as first-line and second-line regimens. Between July 2013 and December 2015, a total of 160 patients in first-line and 70 patients in second-line therapies received rabeprazole 10 mg, minocycline 100 mg, amoxicillin 1000 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. Eradication status was assessed 6-12 weeks after treatment. RMAB therapy achieved the eradication rates of 87.5% (95% confidence interval, 81.9-92.5%, intention-to-treat analysis), 90.9% (85.7-95.5%, modified intention-to-treat analysis), and 92.6% (88.5-96.6%, per-protocol analysis) in first-line therapy in a setting with high antibiotic resistance rates (amoxicillin 3.4%, clarithromycin 39.7%, metronidazole 60.3%, levofloxacin 36.2%, tetracycline 3.4%, and minocycline 6.9%). As for second-line therapy, the eradication rates were 82.9% (74.3-91.4%, intention-to-treat analysis), 86.6% (77.6-94.0%, modified intention-to-treat analysis), and 89.1% (81.3-95.3%, per-protocol analysis). Totally, 24.0% patients had adverse effects, 2.2% discontinued medications, and good compliance was achieved in 94.7%. Poor compliance and minocycline resistance were identified as the risk factors for treatment failure. Significant differences in efficacy existed among the groups of both sensitive (48/51 and 18/20), isolated amoxicillin resistance (1/1 and 0/0), isolated minocycline resistance (2/3 and 1/1), and dual resistance (0/1 and 0/1) in both first-line (p = .004) and second-line (p = .035) therapies. The eradication efficacies of RMAB

  7. Research Progress of Anti-angiogenesis Drugs in the Treatment of Lymphoma

    Directory of Open Access Journals (Sweden)

    Jifeng Feng

    2014-06-01

    Full Text Available As the targeted drugs come into being in recent years, such as monoclonal antibody, great achievements have been made for the treatment of malignant lymphoma (ML. Rituximab, a monoclonal antibody against CD20 whose effective rate is up to 85% in the first-line treatment of lymphoma, has become the standard first-line treatment of multiple B cell lymphomas. However, how to improve the therapeutic efficacy of B lymphoma and reduce reoccurrence rate in drugresistant patients still need to be further studied. And great importance is increasingly attached to the development of new drugs, especially tumor angiogenesis drugs, in which Bevacizumab and Endostatin are studied as the main representative for the treatment of ML. This paper mainly made a review on Current situation and prospects of anti-angiogenesis drugs for the treatment of lymphoma.

  8. Correlation between TS, MTHFR, and ERCC1 gene polymorphisms and the efficacy of platinum in combination with pemetrexed first-line chemotherapy in mesothelioma patients.

    Science.gov (United States)

    Powrózek, Tomasz; Kowalski, Dariusz M; Krawczyk, Paweł; Ramlau, Rodryg; Kucharczyk, Tomasz; Kalinka-Warzocha, Ewa; Knetki-Wróblewska, Magdalena; Winiarczyk, Kinga; Dyszkiewicz, Wojciech; Krzakowski, Maciej; Milanowski, Janusz

    2014-11-01

    The combination of pemetrexed and platinum compound represents the standard regimen for first-line chemotherapy in malignant pleural mesothelioma patients. Pemetrexed is a multitarget antifolate agent that inhibits folate-dependent enzymes (eg, thymidylate synthase [TS]) and thus synthesis of nucleotides and DNA. Expression of TS and folate availability, regulated by gene polymorphisms, have implications for effectiveness of chemotherapy and the outcome of mesothelioma patients. The aim of this retrospective multicenter study was to assess the correlation between TS, 5,10-methylenetetrahydrofolate reductase (MTHFR) and excision repair cross-complementing group 1 (ERCC1) gene polymorphisms and the efficacy of pemetrexed-based first-line chemotherapy of mesothelioma patients. Fifty-nine mesothelioma patients (31 men with a median age of 62 years) treated in first-line chemotherapy with platinum in combination with pemetrexed or pemetrexed monotherapy were enrolled. Genomic DNA was isolated from peripheral blood. Using polymerase chain reaction and high resolution melt methods, the variable number of tandem repeat, the G>C single nucleotide polymorphism (SNP) in these repeats, and 6-base pair (bp) insertion/deletion polymorphism of the TS gene, the SNP of 677C>T in MTHFR, and 19007C>T in the ERCC1 gene were analyzed and correlated with disease control rate, progression-free survival (PFS), and overall survival (OS) of mesothelioma patients. Greater risk of early disease progression (PD), and shortening of PFS and OS were associated with several clinical factors (eg, anemia for early PD and OS), weight loss (for PFS and OS), and previous surgical treatment (for early PD, PFS, and OS). Insertion of 6-bp in both alleles of the TS gene (1494del6) was the only genetic factor that increased the incidence of early progression (P = .028) and shortening of median PFS (P = .06) in patients treated with pemetrexed-based chemotherapy. In multivariate analysis, the 1494del6 in the

  9. Transmission of HIV-1 minority-resistant variants and response to first-line antiretroviral therapy.

    Science.gov (United States)

    Peuchant, Olivia; Thiébaut, Rodolphe; Capdepont, Sophie; Lavignolle-Aurillac, Valérie; Neau, Didier; Morlat, Philippe; Dabis, François; Fleury, Hervé; Masquelier, Bernard

    2008-07-31

    The transmission of drug-resistant HIV-1 can impair the virological response to antiretroviral therapy. Minority-resistant variants have been detected in acute seroconverters. We investigated the clinical relevance of the detection of majority and minority-resistant variants in an observational study in antiretroviral therapy naive, recently infected patients. We included patients infected between 1996 and 2005, with a plasma sample obtained less than 18 months after seroconversion and prior to antiretroviral therapy initiation. Majority-resistant variants were determined by direct population sequencing. Minority-resistant variants were searched by allele-specific PCR for the mutations K103N and M184V in reverse transcriptase and L90M in protease. The association between resistance and viroimmunological response to antiretroviral therapy was estimated by using a piecewise linear mixed model. Majority-resistant variants were detected in 23/172 (13.4%) patients. Patients with majority-resistant variants had a lower mean plasma viral load and higher mean CD4 cell count at baseline compared with those without resistance. The decrease in viral load between 1 and 6 months on antiretroviral therapy was significantly steeper in patients with sensitive viruses compared with those with majority-resistant variants (P = 0.029). Minority-resistant variants were detected in 21/73 (29%) patients with wild-type viruses at sequencing analysis. The presence of minority-resistant variants did not modify baseline viral load and CD4 cell count and did not affect the changes in viral load and CD4 cell count. The transmission of majority-resistant variants, but not minority-resistant variants, influenced the response to antiretroviral therapy in this prospective study. The detection of the transmission of minority-resistant variants warrants further clinical validation.

  10. Infrainguinal vein graft stenosis: cutting balloon angioplasty as the first-line treatment of choice.

    Science.gov (United States)

    Schneider, Peter A; Caps, Michael T; Nelken, Nicolas

    2008-05-01

    The optimal treatment for hemodynamically significant infrainguinal vein bypass graft stenosis is not known. This study compares three options as first choice for the revision of failing infrainguinal vein grafts: cutting balloon angioplasty (CBA), standard percutaneous transluminal balloon angioplasty (PTA), and open surgical revision (OS). Infrainguinal vein bypass graft lesions treated in a single institution during a 12-year period were evaluated. Of these, 161 lesions in 124 infrainguinal bypasses (101 patients) were treated with OS (n = 42), PTA (n = 57), or CBA (n = 62). The initial indication for the bypass in these patients was limb salvage in 73% and claudication in 27%. The primary outcome of interest was the development of vein graft occlusion or significant stenosis (>or=70%) as detected by surveillance duplex ultrasound scanning or arteriography some time after repair. The stenosis-free patency rates at 48 months for OS, CBA, and PTA were 74%, 62%, and 34%, respectively. PTA was associated with an increased risk of treatment failure compared with both OS (hazard ratio [HR], 3.9; P difference between OS and CBA (HR, 1.3 for CBA vs OS, P = .6). Pseudoaneurysms developed in two CBA patients. One ruptured and required interposition graft, and one was monitored. Cutting balloon angioplasty is a reasonable, initial treatment for infrainguinal vein graft stenosis in most patients. It is a safe, minimally invasive, outpatient procedure with patency rates that are comparable to OS and superior to PTA.

  11. First-Line Treatment with Carboplatin plus nab-Paclitaxel and Maintenance Monotherapy with nab-Paclitaxel for a Thymic Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Kunihiko Funaishi

    2017-06-01

    Full Text Available Thymic carcinomas are rare malignant tumors, located in the anterior mediastinum. For the treatment of these carcinomas, several chemotherapy regimens have been suggested, including carboplatin plus paclitaxel. However, because of the rarity of these tumors, the standard chemotherapy regimen has not yet been established. Here, we report a case of thymic carcinoma that responded to first-line carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel therapy with continuation maintenance nab-paclitaxel monotherapy. A 78-year-old male presented to a hospital with the chief complaint of dyspnea. Cardiomegaly was detected on chest X-ray scans, and marked pericardial effusion was observed by echocardiography. Chest computed tomography scans revealed the presence of a mediastinal mass, pericardial thickening, and pericardial effusion. The serum levels of the tumor marker CYFRA 21-1 (cytokeratin-19 fragment were elevated. Eventually, he was diagnosed with squamous cell carcinoma of the thymus, which was staged as cT4N3M0 or stage IV (according to the tumor-node-metastasis classification. Chemotherapy with carboplatin on day 1 and nab-paclitaxel on days 1, 8, and 15, every 4 weeks was initiated. After the administration of 4 cycles of this regimen, the tumor diameter appeared reduced, and the serum CYFRA 21-1 levels were normalized. After a 1-month interval, the serum CYFRA 21-1 levels increased again; therefore, maintenance nab-paclitaxel monotherapy was initiated. At the end of the treatment, the patient experienced a progression-free survival of 10.3 months. Carboplatin plus nab-paclitaxel may be an appropriate alternative first-line treatment for thymic carcinomas. Additionally, maintenance nab-paclitaxel monotherapy may prolong the progression-free survivals of patients with thymic carcinomas.

  12. Cost-effectiveness of adding cetuximab to platinum-based chemotherapy for first-line treatment of recurrent or metastatic head and neck cancer.

    Directory of Open Access Journals (Sweden)

    Malek B Hannouf

    Full Text Available PURPOSE: To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC from the perspective of the Canadian public healthcare system. METHODS: We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%. RESULTS: In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab. CONCLUSION: The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

  13. First-line use of contact aspiration for thrombectomy versus a stent retriever for recanalization in acute cerebral infarction: The randomized ASTER study protocol.

    Science.gov (United States)

    Lapergue, Bertrand; Labreuche, Julien; Blanc, Raphael; Barreau, Xavier; Berge, Jérome; Consoli, Arturo; Rodesch, Georges; Saleme, Susanna; Costalat, Vincent; Bracard, Serge; Desal, Hubert; Duhamel, Alain; Baffert, Sandrine; Mazighi, Mikael; Gory, Benjamin; Turjman, Francis; Piotin, Michel

    2018-01-01

    Rationale Mechanical thrombectomy with a stent retriever is now the standard of care in anterior circulation ischemic stroke caused by large vessel occlusion. New techniques for mechanical thrombectomy, such as contact aspiration, appear promising to increase reperfusion status and improve clinical outcome. Aim We aim at ascertaining whether contact aspiration is more efficient than the stent retriever as a first-line endovascular procedure. Sample size estimates With a two-sided test (alpha = 5%, power = 90%) and an anticipated rate of spontaneous recanalization and catheterization failures of 15%, we estimate that a sample size of 380 patients will be necessary to detect an absolute difference of 15% in primary outcome (superiority design). Methods and design The ASTER trial is a prospective, randomized, multicenter, controlled, open-label, blinded end-point clinical trial. Patients admitted with suspected ischemic anterior circulation stroke secondary to large vessel occlusion, with onset of symptoms contact aspiration or stent retriever in a 1:1 ratio; stratified by center and prior IV thrombolysis. If the assigned treatment technique is not successful after three attempts, another technique will be applied, at the operator's discretion. Study outcomes The primary outcome will be successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b-3) at the end of the endovascular procedures. Secondary outcome will include successful recanalization after the assigned first-line treatment technique alone, procedural times, the need for a rescue technique, complications and modified Rankin Scale at three months. Discussion No previous head to head randomized trials have directly compared contact aspiration versus stent retriever reperfusion techniques. This prospective trial aims to provide further evidence of benefit of contact aspiration versus stent retriever techniques among patients with ischemic stroke.

  14. First-line bevacizumab-containing therapy for breast cancer: results in patients aged≥70 years treated in the ATHENA study.

    Science.gov (United States)

    Biganzoli, L; Di Vincenzo, E; Jiang, Z; Lichinitser, M; Shen, Z; Delva, R; Bogdanova, N; Vivanco, G L; Chen, Z; Cheng, Y; Just, M; Espié, M; Vinholes, J; Hamm, C; Crivellari, D; Chmielowska, E; Semiglazov, V; Dalenc, F; Smith, I

    2012-01-01

    There are limited data on treatment outcomes in the growing population of elderly patients with locally recurrent/metastatic breast cancer (LR/mBC). To gain information on first-line bevacizumab combined with chemotherapy in the elderly, we analyzed data from the ATHENA trial in routine oncology practice. Patients with human epidermal growth factor receptor-2-negative LR/mBC received first-line bevacizumab with standard chemotherapy until disease progression, unacceptable toxicity, or physician/patient decision. We carried out a subgroup analysis of safety and efficacy in patients aged≥70 years. Possible correlations between tolerability and baseline comorbidities or Eastern Cooperative Oncology Group status were explored. Bevacizumab was combined with single-agent paclitaxel in 46% of older patients. Only hypertension and proteinuria were more common in older than in younger patients (grade≥3 hypertension: 6.9% versus 4.2%, respectively; grade≥3 proteinuria: 4.0% versus 1.5%, respectively). Grade≥3 arterial/venous thromboembolism occurred in 2.9% versus 3.3%, respectively. Further analysis revealed no relationship between baseline presence and severity of hypertension and risk of developing hypertension during bevacizumab-containing therapy. Median time to progression was 10.4 months in patients aged≥70 years. These findings suggest that bevacizumab-containing therapy is tolerable and active in patients aged≥70 years. Hypertension was more common than in younger patients but was manageable. We find no evidence precluding the use of bevacizumab in older patients, including those with hypertension, although age may influence chemotherapy choice.

  15. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma.

    Science.gov (United States)

    Herold, Michael; Scholz, Christian W; Rothmann, Frank; Hirt, Carsten; Lakner, Volker; Naumann, Ralph

    2015-09-01

    The randomised, controlled OSHO#39 study showed promising results using first-line mitoxantrone, chlorambucil and prednisolone (MCP) chemotherapy plus rituximab in patients with advanced symptomatic follicular lymphoma (FL) in need of therapy. The aim of this long-term follow-up was to investigate whether clinical benefits are maintained after up to 9 years of observation. Following the 4-year follow-up of OSHO#39, 77 FL patients who received rituximab plus MCP (R-MCP) and 52 patients who received MCP (129 patients alive and not previously censored in total) were followed for 5 additional years in this prospective, non-interventional, observational study. For the efficacy analysis, data were jointly analysed with OSHO#39 data (FL intention-to-treat population: 105 patients R-MCP, 96 MCP). Patients not included in the 5-year follow-up were censored. For surviving patients, median follow-up was 102 months (R-MCP) and 87 months (MCP). Although median overall survival (OS) was not yet reached, OS was longer for patients with R-MCP compared with MCP (p = 0.0057), with 8-year-survival rates of 76.1 versus 55.9%. Further time-to-event data were substantially longer for the R-MCP group than for MCP alone: median progression-free survival (PFS) was 93.4 versus 34.9 months, and median event-free survival (EFS) 89.6 versus 26.5 months. Unplanned subanalyses of patients with and without interferon maintenance showed improved PFS and EFS without an impact on OS. The addition of rituximab to first-line MCP chemotherapy improves clinical outcomes in advanced FL patients and translates into long-term OS benefits. R-MCP remains a promising standard option for this patient group.

  16. Seven-Day Nonbismuth Containing Quadruple Therapy Could Achieve a Grade “A” Success Rate for First-Line Helicobacter pylori Eradication

    Directory of Open Access Journals (Sweden)

    Wei-Chen Tai

    2015-01-01

    Full Text Available This prospective study was to assess the efficacy of nonbismuth containing quadruple therapy as first-line H. pylori treatment and to determine the clinical factors influencing patient outcome. We enrolled 200 H. pylori-infected naïve patients. They were prescribed either a 7-day nonbismuth containing quadruple therapy group (EACM, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily or a 7-day standard triple therapy group (EAC, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by EACM and EAC groups were 95.6% (95% confidence interval [CI] = 89.4%–98.3% and 79.3% (95% CI = 70%–86.4% in the per-protocol analysis (P < 0.001 and 88% (95% CI = 80.2%–93.0% and 73% (95% I = 63.6%–80.3% in the intention-to-treat analysis (P = 0.007. Clarithromycin resistance, metronidazole resistance, and dual clarithromycin and metronidazole resistances were the clinical factors influencing H. pylori eradication in EACM group. Clarithromycin resistance and dual clarithromycin and metronidazole resistances were the influential factor for EAC treatment. In conclusion, the results suggest that 7-day nonbismuth containing quadruple therapy could achieve a grade “A” report card for first-line H. pylori treatment.

  17. Characterization of HIV-1 Near Full-Length Proviral Genome Quasispecies from Patients with Undetectable Viral Load Undergoing First-Line HAART Therapy

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    Brunna M. Alves

    2017-12-01

    Full Text Available Increased access to highly active antiretroviral therapy (HAART by human immunodeficiency virus postive (HIV+ individuals has become a reality worldwide. In Brazil, HAART currently reaches over half of HIV-infected subjects. In the context of a remarkable HIV-1 genetic variability, highly related variants, called quasispecies, are generated. HIV quasispecies generated during infection can influence virus persistence and pathogenicity, representing a challenge to treatment. However, the clinical relevance of minority quasispecies is still uncertain. In this study, we have determined the archived proviral sequences, viral subtype and drug resistance mutations from a cohort of HIV+ patients with undetectable viral load undergoing HAART as first-line therapy using next-generation sequencing for near full-length virus genome (NFLG assembly. HIV-1 consensus sequences representing NFLG were obtained for eleven patients, while for another twelve varying genome coverage rates were obtained. Phylogenetic analysis showed the predominance of subtype B (83%; 19/23. Considering the minority variants, 18 patients carried archived virus harboring at least one mutation conferring antiretroviral resistance; for six patients, the mutations correlated with the current ARVs used. These data highlight the importance of monitoring HIV minority drug resistant variants and their clinical impact, to guide future regimen switches and improve HIV treatment success.

  18. Standard-based comprehensive detection of adverse drug reaction signals from nursing statements and laboratory results in electronic health records.

    Science.gov (United States)

    Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han

    2017-07-01

    We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n   = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation.

  19. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial.

    Science.gov (United States)

    Pignata, Sandro; Scambia, Giovanni; Ferrandina, Gabriella; Savarese, Antonella; Sorio, Roberto; Breda, Enrico; Gebbia, Vittorio; Musso, Pietro; Frigerio, Luigi; Del Medico, Pietro; Lombardi, Alessandra Vernaglia; Febbraro, Antonio; Scollo, Paolo; Ferro, Antonella; Tamberi, Stefano; Brandes, Alba; Ravaioli, Alberto; Valerio, Maria Rosaria; Aitini, Enrico; Natale, Donato; Scaltriti, Laura; Greggi, Stefano; Pisano, Carmela; Lorusso, Domenica; Salutari, Vanda; Legge, Francesco; Di Maio, Massimo; Morabito, Alessandro; Gallo, Ciro; Perrone, Francesco

    2011-09-20

    Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy. Chemotherapy-naive patients with stage IC to IV ovarian cancer (age ≤ 75 years; Eastern Cooperative Oncology Group performance status ≤ 2) were randomly assigned to carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m(2) or to carboplatin AUC 5 plus PLD 30 mg/m(2), every 3 weeks for six cycles. Primary end point was progression-free survival (PFS). With 632 events in 820 enrolled patients, the study would have 80% power to detect a 0.80 hazard ratio (HR) of PFS. Eight hundred twenty patients were randomly assigned. Disease stages III and IV were prevalent. Occurrence of PFS events substantially slowed before obtaining the planned number. Therefore, in concert with the Independent Data Monitoring Committee, final analysis was performed with 556 events, after a median follow-up of 40 months. Median PFS times were 19.0 and 16.8 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.95; 95% CI, 0.81 to 1.13; P = .58). Median overall survival times were 61.6 and 53.2 months with carboplatin/PLD and carboplatin/paclitaxel, respectively (HR, 0.89; 95% CI, 0.72 to 1.12; P = .32). Carboplatin/PLD produced a similar response rate but different toxicity (less neurotoxicity and alopecia but more hematologic adverse effects). There was no relevant difference in global quality of life after three and six cycles. Carboplatin/PLD was not superior to carboplatin/paclitaxel, which remains the standard first-line chemotherapy for advanced ovarian cancer. However, given the observed CIs and the different toxicity, carboplatin/PLD could be considered an alternative to standard therapy.

  20. Resin-based Yttrium-90 microspheres for unresectable and failed first-line chemotherapy intrahepatic cholangiocarcinoma: preliminary results.

    Science.gov (United States)

    Jia, Zhongzhi; Paz-Fumagalli, Ricardo; Frey, Gregory; Sella, David M; McKinney, J Mark; Wang, Weiping

    2017-03-01

    To evaluate the value of resin-based yttrium-90 ( 90 Y) radioembolization for unresectable and failed first-line chemotherapy (cisplatin plus gemcitabine) intrahepatic cholangiocarcinoma (ICC). From February 2006 to September 2015, a retrospective study was conducted of all patients who underwent resin-based 90 Y therapy for unresectable and failed first-line chemotherapy ICC. Tumor response was assessed using modified RECIST criteria; side effects were assessed using Common Terminology Criteria for Adverse Events version 4.03; survivals were calculated from the date of diagnosis of ICC, beginning of first-line chemotherapy and first 90 Y procedure, respectively; effects of factors on survival were analyzed by Cox regression model. Twenty-four patients (eight male and 16 female) were included in this study. Mean 5.6 ± 1.6 cycles of first-line chemotherapy were performed prior to 90 Y treatment. The mean delivered activity of 90 Y was 1.6 ± 0.4 GBq with a total of 27 treatments. Disease control rate was 81.8% at 3 months after 90 Y therapy, with partial response (n = 8, 36.4%), stable disease (n = 10, 45.5%) and progressive disease (n = 6, 18.2%). CA199 changes pre- and 1 month post-treatment were complete (n = 2), partial (n = 2), none (n = 5) and progression (n = 2), respectively. Side effects included fatigue (n = 21, 87.5%), anorexia (n = 19, 79.2%), nausea (n = 15, 62.5%), abdominal pain (n = 10, 58.3%), vomiting (n = 4, 16.7%) and fever (n = 3, 12.5%). Radiation-induced gastrointestinal ulcer was identified in one patient. The mean follow-up was 11.3 ± 6.6 months, and the median survivals from the time of diagnosis of ICC, beginning of first-line chemotherapy and first 90 Y procedure were 24.0, 16.0 and 9.0 months, respectively, and the 6-, 12-, 18-, 24- and 30-month survival after 90 Y therapy were 69.9, 32.6, 27.2, 20.4 and 20.4%, respectively. ECOG performance status (P = 0.002) and lymph node metastases (P = 0

  1. Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Calmy Alexandra

    2012-06-01

    Full Text Available Abstract Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12 were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

  2. Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V

    NARCIS (Netherlands)

    Nijhuis, Monique; Wensing, Annemarie M J; Bierman, Wouter F W; de Jong, Dorien; Kagan, Ron; Fun, Axel; Jaspers, Christian A J J; Schurink, Karin A M; van Agtmael, Michael A; Boucher, Charles A B

    2009-01-01

    BACKGROUND: Virological failure of first-line antiretroviral therapy based on lopinavir boosted with ritonavir (lopinavir/r) has rarely been associated with resistance in protease. We identified a new genotypic resistance pathway in 3 patients who experienced failure of first-line lopinavir/r

  3. The gold industry standard for risk and cost of drug and vaccine development revisited

    NARCIS (Netherlands)

    Pronkers, E.S.; Weenen, T.C.; Commandeur, H.R.; Osterhaus, H.R.; Claassen, H.J.H.M.

    2011-01-01

    Gold dimensions of pharmaceutical drug development indicate that it takes on average 11.9 years, with an investment around US$ 0.8 Billion, to launch one product on the market. Furthermore, approximately 22% of the drug candidates successfully complete clinical testing. These universally

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  6. Suction curettage as first line treatment in cases with cesarean scar pregnancy: feasibility and effectiveness in early pregnancy.

    Science.gov (United States)

    Polat, Ibrahim; Ekiz, Ali; Acar, Deniz Kanber; Kaya, Basak; Ozkose, Burak; Ozdemir, Cagdas; Talay, Hasan; Gedikbasi, Ali

    2016-01-01

    A cesarean scar pregnancy (CSP) is an extremely rare form of an ectopic pregnancy, which is defined as the localization of a fertilized ovum surrounded by uterine muscular fiber and scar tissue. The objective of this study was to discuss the management options for CSPs in a singleton center. In the current study, we discussed the current management options for CSPs based on our 6 years of experience. A retrospective evaluation of diagnosed and treated 26 patients with CSPs in Istanbul Kanuni Sultan Suleyman Training and Research Hospital during a 6-year period was discussed. Suction curettage was performed as first-line treatment in patients with a gestation 2 mm. Twenty-two (84.6%) patients with CSPs were initially treated surgically (curettage and hysterotomy) and four (15.4%) patients were treated medically with methotrexate injections. Vacuum aspiration was performed in 19 patients as a first-line treatment, six of them needed an additional Foley balloon catheter to be inserted for tamponade because of persistent vaginal bleeding. Suction curettage was successful in 12 patients. The treatment rate for suction curettage with or without Foley balloon catheter tamponade was 16 of 19 (84.2%). The early diagnosis of a CSP (7-8 weeks gestation) with a β-hCG level 2 mm can be treated with suction curettage with or without placement of a uterine Foley balloon as curative treatment.

  7. Effect of first-line treatment on second primary malignancies and Richter's transformation in patients with CLL.

    Science.gov (United States)

    Maurer, C; Langerbeins, P; Bahlo, J; Cramer, P; Fink, A M; Pflug, N; Engelke, A; von Tresckow, J; Kovacs, G; Stilgenbauer, S; Wendtner, C-M; Müller, L; Ritgen, M; Seiler, T; Fischer, K; Hallek, M; Eichhorst, B

    2016-10-01

    This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter's transformations (RTs) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N=191) or a RT (N=75). Solid tumors (N=115; 43.2% of all second neoplasias) appeared most frequently, followed by RTs (N=75; 28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1; PHR 1.7; P=0.01), co-morbidities (HR 1.6; P=0.01) and number of subsequent treatments⩾1 (HR 12.1; P10 U/l at trial enrollment (HR 3.9; P=0.02), non-response to first-line treatment (HR 3.6; PHR 30.2; P<0.001) were independently associated with increased risk for RT.

  8. Single parameter wrist ultrasonography as a first-line screening examination in suspected carpal tunnel syndrome patients.

    Science.gov (United States)

    Kurca, E; Nosal, V; Grofik, M; Sivak, S; Turcanova-Koprusakova, M; Kucera, P

    2008-01-01

    Carpal tunnel syndrome (CTS) is the most common form of peripheral nerve entrapment. Electromyography with selected nerve conduction studies (NCS) is an accepted diagnostic tool in CTS patients. Ultrasonography presents a widely available and low cost investigation method and its position in CTS diagnostics needs further clarification with concrete recommendations for clinical practice. A prospective study of 37 patients with 74 wrists (59 wrists with suspected CTS) was done. Normative data were obtained from a control group of 25 healthy persons (50 wrists) age and sex matched. All persons underwent ultrasonographic examination (median nerve cross-sectional area at carpal tunnel entrance measurement--CSA) and median NCS studies (distal motor and sensory latency measurement--DML and DSL). CSA has a sensitivity of 93% (CI 84-97%) and specificity of 96% (CI 87-99%) in our patients group. Conventional first-line NCS studies results in our patients groupare as follows: DML sensitivity 58% (CI 45-69%) and specificity 100% (CI 93-100%); DSL sensitivity 88% (CI 78-94%) and specificity 94% (CI 84-98%). We recommend the use of single-parameter wrist ultrasonography as a first-line screening laboratory method in suspected CTS diagnosis (Ref. 14). Full Text (Free, PDF) www.bmj.sk.

  9. Metastatic esophagogastric adenocarcinoma: trends in first-line treatment and predictive factors for the implementation of HER2 testing in clinical practice during the first year after trastuzumab market approval.

    Science.gov (United States)

    Gencer, Deniz; Al-Batran, Salah-Eddin; Dada, Reyad; Hünerlitürkoglu, Ali-Nuri; Gonnermann, Michael; Kegel, Thomas; Scheiber, Harald; Jordan, Wolf-Oliver; Burkholder, Iris; Kellermann, Lenka; Hofheinz, Ralf-Dieter

    2013-02-01

    Little is known about the use of first-line chemotherapy in clinical practice in patients with advanced esophagogastric adenocarcinoma, and no data have been published regarding potential obstacles for the implementation of molecular testing for targeted agents in this patient group. Here, we sought to evaluate factors influencing treatment decisions with special focus on the implementation of HER2 testing during the first year after trastuzumab market approval in Germany. A total of 754 patients undergoing treatment decisions for palliative first-line therapy in 2010 were documented using Therapiemonitor(®). Drug use and intensity of first-line treatment were analyzed. Data on HER2 testing and test algorithm are described, and variables influencing HER2 testing were selected using bivariate analysis. Significant factors were included in a multivariate logistic regression analysis. Compared with previous years, treatment intensity has further increased. The use of chemotherapy triplets rose from 10.1 % in 2006 to 60.3 % in 2010. In 2010, 49.1 % of patients were tested for HER2 and in 52.2 % of these patients the currently proposed test algorithm was used. Using multivariate logistic regression analysis age ≥67 years and "initiating institution: practice" were found to negatively impact the likelihood of HER2 testing, while treatment goal "prevention of progression", multiple metastases and a Karnofsky status >80 % showed positive correlation with HER2 testing. The tendency to use more intensive first-line chemotherapy regimens in patients with advanced esophagogastric adenocarcinoma continued in 2010. Only a minority of patients had an access to the appropriate molecular diagnostics and therefore to treatment with trastuzumab. The access was limited due to the preselection following individual, clinical and institutional factors.

  10. Physicochemical and elemental studies of Hydrocotyle javanica Thunb. for standardization as herbal drug

    Directory of Open Access Journals (Sweden)

    Manab Mandal

    2017-11-01

    Conclusions: Hence the present physicochemical and elements studies reveals that the plant Hydrocotyle javanica Thunb. could be a potent source of herbal preparation as well as a safe and novel synthetic antibacterial drug.

  11. Is intravenous lorazepam really more effective and safe than intravenous diazepam as first-line treatment for convulsive status epilepticus? A systematic review with meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Brigo, Francesco; Bragazzi, Nicola Luigi; Bacigaluppi, Susanna; Nardone, Raffaele; Trinka, Eugen

    2016-11-01

    Some guidelines or expert consensus indicate that intravenous (IV) lorazepam (LZP) is preferable to IV diazepam (DZP) for initial treatment of convulsive status epilepticus (SE). We aimed to critically assess all the available data on efficacy and tolerability of IV LZP compared with IV DZP as first-line treatment of convulsive SE. Systematic search of the literature (MEDLINE, CENTRAL, EMBASE, ClinicalTrials.gov) to identify randomized controlled trials (RCTs) comparing IV LZP versus IV DZP used as first-line treatment for convulsive SE (generalized or focal). Inverse variance, Mantel-Haenszel meta-analysis to obtain risk ratio (RR) with 95% confidence intervals (CI) of following outcomes: seizure cessation after drug administration; continuation of SE requiring a different drug; seizure cessation after a single dose of medication; need for ventilator support; clinically relevant hypotension. Five RCTs were included, with a total of 656 patients, 320 randomly allocated to IV LZP and 336 to IV DZP. No statistically significant differences were found between IV LZP and IV DZP for clinical seizure cessation (RR 1.09; 95% CI 1.00 to 1.20), continuation of SE requiring a different drug (RR 0.76; 95% CI 0.57 to 1.02), seizure cessation after a single dose of medication (RR 0.96; 95% CI 0.85 to 1.08), need for ventilator support RR 0.93; 95% CI 0.61 to 1.43, and clinically relevant hypotension. Despite its favorable pharmacokinetic profile, a systematic appraisal of the literature does not provide evidence to strongly support the preferential use of IV LZP as first-line treatment of convulsive SE over IV DZP. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Valproic Acid versus Lamotrigine as First-line Monotherapy in Newly Diagnosed Idiopathic Generalized Tonic -Clonic Seizures in Adults - A Randomized Controlled Trial.

    Science.gov (United States)

    Giri, Vishal Prakash; Giri, Om Prakash; Khan, Farhan Ahmad; Kumar, Narendra; Kumar, Ajay; Haque, Ataul

    2016-07-01

    Idiopathic Generalized Tonic-Clonic Seizures (GTCS) are frequently encountered in adults. Their successful control is necessary to improve the quality of life of these patients. Valproic acid is a simple branched-chain carboxylic acid and lamotrigine is a phenyltriazine derivative. Opinions differ in regards to their effectiveness in idiopathic GTCS. To compare the effectiveness of valproic acid and lamotrigine in newly diagnosed adults with idiopathic generalized tonic-clonic seizures. The present prospective randomized study was conducted on 60 patients suffering from idiopathic GTCS. Thirty patients received valproic acid and rest 30 patients received lamotrigine. All patients were followed regularly monthly for one year for treatment response and adverse effects. After 12 months follow-up, 76.67% patients taking valproic acid and 56.67% patients taking lamotrigine were seizure-free. Common adverse effects recorded were nausea, dyspepsia, headache and skin rash. Valproic acid is more effective than lamotrigine as first-line drug in the treatment of adults with newly diagnosed idiopathic generalized tonic-clonic seizures.

  13. Algorithms in the First-Line Treatment of Metastatic Clear Cell Renal Cell Carcinoma--Analysis Using Diagnostic Nodes.

    Science.gov (United States)

    Rothermundt, Christian; Bailey, Alexandra; Cerbone, Linda; Eisen, Tim; Escudier, Bernard; Gillessen, Silke; Grünwald, Viktor; Larkin, James; McDermott, David; Oldenburg, Jan; Porta, Camillo; Rini, Brian; Schmidinger, Manuela; Sternberg, Cora; Putora, Paul M

    2015-09-01

    With the advent of targeted therapies, many treatment options in the first-line setting of metastatic clear cell renal cell carcinoma (mccRCC) have emerged. Guidelines and randomized trial reports usually do not elucidate the decision criteria for the different treatment options. In order to extract the decision criteria for the optimal therapy for patients, we performed an analysis of treatment algorithms from experts in the field. Treatment algorithms for the treatment of mccRCC from experts of 11 institutions were obtained, and decision trees were deduced. Treatment options were identified and a list of unified decision criteria determined. The final decision trees were analyzed with a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees. The most common treatment recommendations were determined, and areas of discordance were identified. The analysis revealed heterogeneity in most clinical scenarios. The recommendations selected for first-line treatment of mccRCC included sunitinib, pazopanib, temsirolimus, interferon-α combined with bevacizumab, high-dose interleukin-2, sorafenib, axitinib, everolimus, and best supportive care. The criteria relevant for treatment decisions were performance status, Memorial Sloan Kettering Cancer Center risk group, only or mainly lung metastases, cardiac insufficiency, hepatic insufficiency, age, and "zugzwang" (composite of multiple, related criteria). In the present study, we used diagnostic nodes to compare treatment algorithms in the first-line treatment of mccRCC. The results illustrate the heterogeneity of the decision criteria and treatment strategies for mccRCC and how available data are interpreted and implemented differently among experts. The data provided in the present report should not be considered to serve as treatment recommendations for the management of treatment-naïve patients with multiple metastases from metastatic clear cell renal cell carcinoma outside

  14. First-line antiretroviral therapy and dyslipidemia in people living with HIV-1 in Cameroon: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Kengne André

    2011-09-01

    Full Text Available Abstract Background Data on lipid profile derangements induced by antiretroviral treatment in Africa are scarce. The aim of this study was to determine the prevalence and characteristics of lipid profile derangements associated with first-line highly active antiretroviral therapy (ART among Cameroonians living with human immunodeficiency virus (HIV infection. Methods This cross-sectional study was conducted between November 2009 and January 2010, and involved 138 HIV patients who had never received ART (ART-naive group and 138 others treated for at least 12 months with first line triple ART regimens that included nevirapine or efavirenz (ART group. Lipid profile was determined after overnight fast and dyslipidemia diagnosed according to the US National Cholesterol Education Program III criteria. Data comparison used chi-square test, Student t-test and logistic regressions. Results The prevalence of total cholesterol ≥ 200 mg/dl was 37.6% and 24.6% respectively in ART group and ART-naive groups (p = 0.019. The equivalents for LDL-cholesterol ≥ 130 mg/dl were 46.4% and 21% (p ≤ 0.001. Proportions of patients with total cholesterol/HDL-cholesterol ratio ≥ 5 was 35.5% in ART group and 18.6% in ART-naive group (p ≤ 0.001. The distribution of HDL-cholesterol and triglycerides was similar between the two groups. In multivariable analysis adjusted for age, sex, body mass index, CD4 count and co-infection with tuberculosis, being on ART was significantly and positively associated with raised total cholesterol, LDL-cholesterol and TC/HDL cholesterol. The adjusted odd ratios (95% confidence interval, p-value ART-treated vs. ART-naïve was 1.82 (1.06-1.12, p = 0.02 for TC ≥ 200 mg/dl; 2.99 (1.74-5.15, p Conclusions First-line antiretroviral therapy that includes nonnucleoside reverse transcriptase inhibitors is associated with pro-atherogenic adverse lipid profile in people with HIV-1 infection compared to untreated HIV-infected subjects in

  15. Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Davidson Neville

    2004-07-01

    Full Text Available Abstract Background This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer. Methods Sixty-three patients received irinotecan (250 or 300 mg/m2, 30- to 90-minute intravenous infusion on day 1, immediately followed by folinic acid (20 mg/m2/day and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion days 1 to 5, every four weeks. Results Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3–4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m2. The response rate for the evaluable patient population was 36% (13/36, and 44% (16 patients had stable disease (including 19% of minor response. For the intention-to-treat population, the response rate was 29% (14/49 and 35% (17 patients stable disease (including 14% of minor response. The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3–4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related. Conclusions This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3–4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil

  16. The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden

    Directory of Open Access Journals (Sweden)

    Murphy Daniel R

    2012-10-01

    Full Text Available Abstract Background This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO and Glucocorticoid-induced osteoporosis (GIOP. The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. Methods A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated. For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5. Results The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. Conclusions The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO

  17. Nomogram-based Prediction of Overall Survival in Patients with Metastatic Urothelial Carcinoma Receiving First-line Platinum-based Chemotherapy

    DEFF Research Database (Denmark)

    Necchi, Andrea; Sonpavde, Guru; Lo Vullo, Salvatore

    2017-01-01

    , AND PARTICIPANTS: Individual patient-level data from 29 centers were collected, including metastatic UC and first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011. INTERVENTION: First-line, platinum-based, combination chemotherapy. OUTCOME MEASUREMENTS...... (development: 687, validation: 333). In a platinum-stratified Cox model, significant variables for OS were performance status (pchemotherapy (p=0......-line chemotherapy for metastatic UC. PATIENT SUMMARY: We proposed two models for estimating overall survival of patients with metastatic urothelial carcinoma receiving first-line, platinum-based chemotherapy. These nomograms have been developed on real-world patients who were treated outside of clinical trials...

  18. Two-year outcome of first-line antiretroviral therapy among HIV-1 vertically-infected children in Hanoi, Vietnam.

    Science.gov (United States)

    Pham, H V; Ishizaki, A; Nguyen, L V; Phan, C T T; Phung, T T B; Takemoto, K; Pham, A N; Bi, X; Khu, D T K; Ichimura, H

    2015-10-01

    A retrospective analysis of 86 HIV-1 vertically-infected Vietnamese children with a follow-up period >24 months after initiating antiretroviral therapy (ART) was performed from 2008 to 2012, to assess the outcome of first-line ART in resource-limited settings. Of the 86 children, 68 (79.1%) were treated successfully (plasma HIV-1 viral load [VL] failure groups was observed in VL, CD4(+) T-cell count or clinical stage at baseline; age at ART start; or ART regimen. All 14 children with VL >5000 copies/ml, one of four children with VL 1000-5000 copies/ml and none with VL failures among HIV-1 vertically-infected children in resource-limited settings. © The Author(s) 2015.

  19. Can an NTI-tss device be effective as a first-line therapy in patients with TMD myofascial pain?

    Science.gov (United States)

    Hasanoglu Erbasar, G N; Alpaslan, C; Eroglu Inan, G

    2017-08-01

    This study was conducted to evaluate whether integrating a nociceptive trigeminal inhibition-tension suppression system (NTI-tss) device with first-line therapy of myofascial pain, which includes guidance, assurance, counselling and behavioural changes, would be more effective in alleviating symptoms. This randomised controlled clinical trial included 40 patients who were clinically diagnosed with myofascial pain according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Patients were randomly divided into two groups: the first group comprised patients who received guidance, assurance, counselling and behavioural changes; an NTI-tss device was integrated to this protocol in the second group. Both groups exhibited reduction in pain levels and improvement of jaw function compared with baseline values, but the difference was not significant. Both groups demonstrated improvements in 6 weeks; however, the integration of NTI-tss device into the therapy protocol did not provide any additional benefit in relieving symptoms of myofascial pain. © 2017 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Paul Zarogoulidis

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Elanie Steyn

    2014-06-01

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

  2. [Cooperative research and educational center for breeding and standardization of medicinal plants and drug development between Japan and China].

    Science.gov (United States)

    Tanaka, Hiroyuki

    2009-04-01

    A project "Cooperative research and educational center for breeding and standardization of medicinal plants and drug development between Japan and China" was launched in 2006 with the support of National Natural Science Foundation of China (NSFC) and Japan Society for the Promotion of Science (JSPS). The project focuses on medicinal plants that are important sources of traditional medicines and modern drugs. Many of these plants exist in Asian countries and have been utilized in health care to maintain quality of life. Recently, the short supply of some important medicinal plants, like Glycyrrhiza sp. and Ephedra sp. has become an issue in Japan and China. We believe that cooperative research by many specialist researchers is a prerequisite for overcoming this problem and for establishing a supply of these resources with their highly added values. Furthermore, with our group's participating researchers utilizing state-of-the-art drug evaluation methods in pharmacological and pharmacutical sciences, the development of new drugs and treatment candidates using the collaborative resources of this project, which include distinguished natural chemists, is anticipated. Another important aim of the project is to foster young scientists. In the project, we are encouraging them to continue their studies to produce new findings regarding traditional medicines and drug development.

  3. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro.

    Science.gov (United States)

    Weissenstein, Ulrike; Kunz, Matthias; Urech, Konrad; Baumgartner, Stephan

    2014-01-08

    Given the importance of complementary and alternative medicine (CAM) to cancer patients, there is an increasing need to learn more about possible interactions between CAM and anticancer drugs. Mistletoe (Viscum album L.) belongs to the medicinal herbs that are used as supportive care during chemotherapy. In the in vitro study presented here the effect of standardized mistletoe preparations on the cytostatic and cytotoxic activity of several common conventional chemotherapeutic drugs was investigated using different cancer cell lines. Human breast carcinoma cell lines HCC1937 and HCC1143 were treated with doxorubicin hydrochloride, pancreas adenocarcinoma cell line PA-TU-8902 with gemcitabine hydrochloride, prostate carcinoma cell line DU145 with docetaxel and mitoxantrone hydrochloride and lung carcinoma cell line NCI-H460 was treated with docetaxel and cisplatin. Each dose of the respective chemotherapeutic drug was combined with Viscum album extract (VAE) in clinically relevant concentrations and proliferation and apoptosis were measured. VAE did not inhibit chemotherapy induced cytostasis and cytotoxicity in any of our experimental settings. At higher concentrations VAE showed an additive inhibitory effect. Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to chemotherapeutic drugs and VAE simultaneously.

  4. 77 FR 48491 - Regulatory New Drug Review: Solutions for Study Data Exchange Standards; Notice of Meeting...

    Science.gov (United States)

    2012-08-14

    ... Exchange Standards'' the purpose of which is to solicit input from industry, technology vendors, and other members of the public regarding the advantages and disadvantages of current and emerging open, consensus... technology. Moreover, it is not supported and maintained by an open, consensus-based standards development...

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

    Directory of Open Access Journals (Sweden)

    Noemí Reguart

    2010-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-04-15

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

  7. Rituximab as first-line treatment for the management of adult patients with non-severe hemophilia A and inhibitors.

    Science.gov (United States)

    Lim, M Y; Nielsen, B; Lee, K; Kasthuri, R S; Key, N S; Ma, A D

    2014-06-01

    The role of immunosuppression in the management of patients with congenital hemophilia and inhibitors is uncertain. The use of rituximab has been limited to case reports and case series. In most reports, rituximab was used as second-line or third-line treatment following failure of conventional immune tolerance induction therapy, and more commonly in pediatric patients. The objective of this study was to describe our experience with rituximab for the eradication of factor VIII inhibitors in adult patients with non-severe hemophilia A. We retrospectively reviewed the medical records of adult patients with non-severe hemophilia A and a diagnosis of FVIII inhibitor treated with rituximab (four weekly doses of 375 mg m(-2) ) as first-line treatment at our hemophilia center. We identified nine consecutive adult patients with hemophilia A (moderate, n = 5; mild, n = 4) at our institution between 2000 and 2013, with a median age of 54 years (range, 24-77 years) at the time of inhibitor diagnosis. No patient received concomitant immune tolerance induction therapy. All nine patients had successful eradication of FVIII inhibitors. The median time from the first dose of rituximab to a clinical response was 95 days (range, 12-278 days). The median follow-up was 56 months (range, 13-139 months). Following inhibitor eradication, eight patients were rechallenged with FVIII concentrates. Two patients developed inhibitor recurrence associated with surgery. This case series demonstrates that rituximab is a useful first-line treatment to achieve sustained inhibitor eradication in adult patients with non-severe hemophilia A. © 2014 International Society on Thrombosis and Haemostasis.

  8. Is open decortication superior to fibrinolytic therapy as a first line treatment in the management of pleural empyema?

    Science.gov (United States)

    Ahmed, Sultan; Azam, Hammad; Basheer, Imran

    2016-01-01

    To confirm that either Fibrinolytic therapy or open decortication which of the two is an effective First line treatment of pleural empyema. This prospective comparative study was conducted in the department of surgery Sheikh Zayed Medical College and Hospital, Rahim Yaar Khan. Seventy eight (78) patients were included in this study. There were two groups of patients; Group I (n=35) patients treated with fibrinolytic therapy, Group II (n=43) patients treated with open decortication. Data was entered and analyzed in SPSS v16. Student's t-test was used for comparison of quantitative variables. Chi-square and Fisher's Exact test were used for comparison of qualitative variables. P-value ≤ 0.05 was taken as significant difference. There was no significant difference in base baseline characteristics of patients of Group I and II. Incidence of comorbidities was also same between the groups. Most of the patients in Group I and II were in empyema stage III. Fluid cultures was positive in 33 (94.3%) patients in group I and 39 (90.7%) patients in group II. 30 (85.7%) was successfully treated using fibrinolytic therapy but this therapy failed in five (14.3%) patients, two of these patients expired within the hospital. There was only one (2.3%) treatment failure in open decortication Group that patient expired within the hospital (p-value 0.04). Overall duration of hospitalization was significantly high in fibrinolytic group, this was 17.6± 1.95 days versus 12.09± 2.18 days in open decortication group (p-value<0.0001). There was no significant difference regarding operative mortality within the two groups. Open Drainage is associated with better outcomes as compared to fibrinolytic therapy when used as a First line treatment of empyema.

  9. [Cuadruple concomitant non-bismuth therapy vs. classical triple therapy as first line therapy for Helicobacter pylori infection].

    Science.gov (United States)

    Campillo, Ana; Ostiz, Miriam; Amorena, Edurne; Kutz, Marcos; La Iglesia, Matilde

    2016-09-02

    In a previous study we found that the classical triple therapy for Helicobacter pylori (H. pylori) had low efficacy (under 70%) in our area. After this finding, in mid 2012 quadruple concomitant therapy started to be prescribed in our hospital. The aim of the present study is to compare the efficacy of classical triple therapy and quadruple concomitant therapy without bismuth. Observational retrospective study of prescribed treatments between 1st January 2012 and 5th May 2014 and their efficacy. During the study period 510 patients were prescribed a first line therapy; in 179 cases (35,1%) the combination amoxiciline+clarithromicine+PPI was prescribed during 7-14 days, and 298 patients (58,4%) were treated with amoxicillin+clarithromycin+metronidazole+PPI for 10 days. The quadruple concomitant therapy had a higher efficacy than the classical triple therapy, both in an "intention to treat" (84.8% vs. 65.7%, P=.001) and "per protocol" (86.9% vs. 67.2%, P=.001) analysis. Triple therapy had a higher efficacy when it was prescribed for 10 days compared to 7 days (77.9% vs. 56.5%, P=.005 per "intention to treat" and 77.9% vs. 58.5%, P=.011 "per protocol"). When quadruple concomitant therapy was compared with classical triple therapy prescribed over 10 days no significant differences were found. In our setting, cuadruple concomitant therapy without bismuth has a high efficacy as first line therapy for H. pylori eradication, with much better results than classical triple therapy in the way that it is most widely prescribed (short courses of 7-day with a single dose of omeprazole). Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  10. Prevalence of HIV-Associated Metabolic Abnormalities among Patients Taking First-Line Antiretroviral Therapy in Uganda.

    Science.gov (United States)

    Omech, Bernard; Sempa, Joseph; Castelnuovo, Barbara; Opio, Kenneth; Otim, Marcel; Mayanja-Kizza, Harriet; Colebunders, Robert; Manabe, Yukari C

    2012-01-01

    Introduction. While the introduction of highly active antiretroviral therapy decreased HIV-related morbidity and mortality rates in the sub-Saharan Africa, a subsequent increase in metabolic abnormalities has been observed. We sought to determine the prevalence of HIV-associated metabolic abnormalities among patients on first-line antiretroviral therapy (ART) in an ART clinic in Kampala, Uganda. Methods. Four hundred forty-two consecutive patients on first-line ART for at least 12 months were screened for eligibility in a cross-sectional study, and 423 were enrolled. Pre-ART patient characteristics were abstracted from medical charts, examinations included anthropometric measurement and physical assessment for lipodystrophy. Results. The prevalence of hyperglycemia and dyslipidemia was 16.3% (69/423) and 81.5% (345/423), respectively. Prevalence of dyslipidemia between stavudine- and zidovudine-based regimens (91% versus 72%; P < 0.001). Being on stavudine (aOR 4.79, 95%, 2.45-9.38) and peak body weight (aOR 1.44, 95% CI 1.05-1.97) were independent risk factors for dylipidemia. Stavudine (aOR 0.50, 95% CI  0.27-0.93) use was associated with lower risk for hyperglycemia while, and older age (aOR 1.31, 95% CI 1.11-1.56) and having a family history of DM (aOR 2.18, 95% CI 1.10-4.34) were independent risk factors for hyperglycemia. Conclusions. HIV-associated metabolic complications were prevalent among patients on thymidine analogue-containing ART regimens. Screening for lipid and glucose abnormalities should be considered in ART patients because of cardiovascular risks.

  11. Efficacy and safety of bevacizumab in combination with irinotecan and capecitabine in first-line treatment of metastatic colorectal carcer

    Directory of Open Access Journals (Sweden)

    Jungić Saša

    2017-01-01

    Full Text Available Background/Aim. The efficacy and safety of bevacizumab (BEV in combination with capecitabin and irinotecan in first-line therapy for patients with metastatic colorectal cancer (mCRC were studied. In order to improve safety and efficacy of chemotherapy, as well as to reduce adverse reactions to a minimum, doses of active agents applied were changed in relation to previously employed schedules. Methods. Patients with histologically documented mCRC with no previously received chemotherapy or with received adjuvant or neoadjuvant chemotherapy, which ended 6 months before capecitabin treatment (1000 mg/m2 per os from the 2nd to 8th day of each cycle, irinotecan (175 mg/m2 iv every 2 weeks, plus bevacizumab (5 mg/kg iv every 2 weeks were observed. Results. This prospective study included 35 patients of both sexes. The overall response rate (ORR of 28.6%, partial response (PR of 28.6%, progressive disease (PD of 28.6% and stable disease (SD of 42.8% were found. The progressionfree survival (PFS of the analyzed patients was 11.3 (95% CL: 9.1–12.9 months while overall survival (OS of the included patients was 25.2 (95% CL: 17.4–28.4 months and 117 adverse effects were recorded in 24 patients. Alopecia, nausea and vomiting, hemorrhage, hand-foot syndrome, diarrhea, abdominal pain, proteinuria, and hypertension (51.4%, 37.1%, 37.1%, 25.7%, 22.8%, 20.0%, 20.0% and 17.1%, respectively were most frequently observed adverse effects. Conclusion. The results of this clinical trial support and recommend the use of bevacizumab plus capecitabin and irinotecan in the doses and schedule applied throughout this study as the first-line treatment of mCRC patients.

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

    Science.gov (United States)

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

    2017-04-01

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

  13. Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine.

    Science.gov (United States)

    Lee, Choong-kun; Jung, Minkyu; Choi, Hye Jin; Kim, Hye Ryun; Kim, Hyo Song; Roh, Mi Ryung; Ahn, Joong Bae; Chung, Hyun Cheol; Heo, Su Jin; Rha, Sun Young; Shin, Sang Joon

    2015-10-01

    There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m(2) on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

  14. Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

    Science.gov (United States)

    Arenas-Pinto, Alejandro; Thompson, Jennifer; Musoro, Godfrey; Musana, Hellen; Lugemwa, Abbas; Kambugu, Andrew; Mweemba, Aggrey; Atwongyeire, Dickens; Thomason, Margaret J; Walker, A Sarah; Paton, Nicholas I

    2016-02-01

    Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.

  15. A Postauthorization Survey to Document the Therapeutic Management of Oxaliplatin as a First-Line Chemotherapy Regimen in South Africa in Patients with Metastatic Colorectal Cancer

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    Lydia M. Dreosti

    2014-01-01

    Full Text Available Oxaliplatin is a standard first-line treatment for metastatic colorectal cancer. The objectives were to document the therapeutic management of oxaliplatin in South Africa, determine the incidence and severity of sensory neuropathy, and record the 2-year survival rate. Meccelox was a prospective, noncontrolled, open label, multicentre, observational survey of adult patients with stage IV metastatic colorectal cancer treated with oxaliplatin-based chemotherapeutic regimens. The study was conducted from August 2007 to November 2011 in 29 sites in South Africa by 66 participating treating physicians. Among the 195 enrolled patients, 61% were treated with FOLFOX regimen (5-fluorouracil/folinic acid plus oxaliplatin for an average of 12 cycles and 32% patients were treated with XELOX (capecitabine plus oxaliplatin for an average of 6–8 cycles, with the main reason for discontinuation being completion of the preplanned prescribed regimen. In Meccelox survey, 80% of patients were treated with intent of palliation. Overall 64% of patients reported symptoms of sensory neuropathy. The 2-year survival rate was 30%. Conclusions. Patients received a specified preplanned number of chemotherapy cycles rather than being treated until disease progression or toxicity. Both the incidence of neuropathy and the 2-year survival rate were less than previous reports.

  16. Promoting wellness for patients on androgen deprivation therapy: why using numerous drugs for drug side effects should not be first-line treatment.

    Science.gov (United States)

    Moyad, Mark A; Roach, Mack

    2011-08-01

    The controversy over androgen deprivation therapy (ADT) for prostate cancer seems to have shifted over the past decade. The issue of adverse events or side effects now seems to dominate over that of clinical efficacy. However, this article provides evidence that questions the treatment of these side effects with numerous prescription medications that have their own unique toxicity profile in patients with nonmetastatic disease. The hope is that patients will no longer be considered passive participants in the prevention and treatment of ADT side effects, now that information is available to help mitigate many of these effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Clinical trials information in drug development and regulation : existing systems and standards

    NARCIS (Netherlands)

    Valkenhoef, Gert van; Tervonen, Tommi; Brock, Bert de; Hillege, Hans

    2012-01-01

    Clinical trials provide pivotal evidence on drug efficacy and safety. The evidence, information from clinical trials, is currently used by regulatory decision makers in marketing authorization decisions, but only in an implicit manner. For clinical trials information to be used in a transparent and

  18. [Actuality investigation on general crude drugs and its quality standard of Tibetan medicine].

    Science.gov (United States)

    Zhong, Guoyue; Zhou, Fucheng; Shi, Shangmei; Zhou, Huarong; Yu, Jiangyong; Ping, A; Liu, Haiqing; Dawa, Zhuoma

    2012-08-01

    To provide a reference for the standardization of Tibetan medicine. Investigating the hospital preparations , Tibetan formulated products, and the literature recorded preparations in the Tibetan, Qinghai, Gansu, Sichuan and Yunnan Provinces. Moreover, the varieties, original bases and standard conditions of these preparations were analyzed. According to Chinese Pharmacopoeia, Tibetan medicine part of ministerial standard, Tibetan medicine standards and related monographs and literatures of Tibetan medicine. About 502 various of herbs were used in 711 hospital preparations from 40 medical institutions, Tibetan formulated products from Tibetan pharmaceutical factories, and 439 literature recorded preparations. About 154 herbs were used in more than 10 preparations, while most of them were Tibetan endemic species. About 416 medicinal varieties have the original documented basis, including 287 botanicals, 78 animal medicines, 51 mineral medicines, involving a total of 94 families, 261 genus and 643 species of botanical origin (including species of the next grade), 35 families, 52 genera and 61 species of the animal origin (including species of the next grade). About 122 varieties of herbs were cross-used in the traditional Chinese medicine and Tibetan medicine, about 80% of Tibetan medicinal varieties are produced in the Tibetan Areas of Tibet Plateau. About 293 medicinal varieties were contained in the above standards. Most of the herb's standards only contains character, indentification, and examination, except for 8 varieties which were recorded in the Chinese Pharmacopoeia (2010) as Tibetan medicine. This study of quality standard of Tibetan medicine should have an emphasis on the general varieties, especially the study on the arrangement research and the efficacious material basis of the varieties and the original, as well as term standardization of the National Medicine.

  19. Evaluation of nursing care associated with infants born to mothers with drugs abuse and its comparison with the standards in selected hospitals in Kerman 2013-2014.

    Science.gov (United States)

    Mahdavi Khaki, Z; AbbasZadeh, A; Rassoli, M; Zayeri, F

    2015-01-01

    Background. Pregnancy of women addicted to drugs is a public health problem in most countries, leading to various problems in the mother, the fetus, and the newborn. Since these babies are at risk of various complications and even death, competent and appropriate care of these children is needed. The present study aimed to assess the quality of nursing care provided to newborns and its comparison with the existing standards in infants and neonatal intensive care units of the selected Hospitals in Kerman. Materials and Methods. In this descriptive conducted study, 400 nursing cares, provided to infants born to mothers with drugs abuse, observed and were compared to standard checklists provided by the latest resources and the world's scientific papers. The checklist provided was based on the evaluation of infants and included two distinct categories: non-drug therapy and drug treatment. Finally, the data were analyzed. Results. The consistency quality of the nursing cares provided to infants born to mothers with drugs abuse was evaluated with the existing standards in children, 73% receiving non-drug therapy and 81% of the infants receiving drug treatment. Conclusion. Compared to standards in the normal state, nursing care was associated with babies born to mothers with drugs abuse. The reduction in the incidence of morbidity and mortality in this group of infants was expected in the case of familiarity and training of nursing and the use of caring standards, particularly when applying non-drug therapy.

  20. Size and usage patterns of private TB drug markets in the high burden countries.

    Science.gov (United States)

    Wells, William A; Ge, Colin Fan; Patel, Nitin; Oh, Teresa; Gardiner, Elizabeth; Kimerling, Michael E

    2011-05-04

    Tuberculosis (TB) control is considered primarily a public health concern, and private sector TB treatment has attracted less attention. Thus, the size and characteristics of private sector TB drug sales remain largely unknown. We used IMS Health data to analyze private TB drug consumption in 10 high burden countries (HBCs), after first mapping how well IMS data coverage overlapped with private markets. We defined private markets as any channels not used or influenced by national TB programs. Private markets in four countries--Pakistan, the Philippines, Indonesia and India--had the largest relative sales volumes; annually, they sold enough first line TB drugs to provide 65-117% of the respective countries' estimated annual incident cases with a standard 6-8 month regimen. First line drug volumes in five countries were predominantly fixed dose combinations (FDCs), but predominantly loose drugs in the other five. Across 10 countries, these drugs were available in 37 (loose drug) plus 74 (FDCs) distinct strengths. There were 54 distinct, significant first line manufacturers (range 2-11 per country), and most companies sold TB drugs in only a single study country. FDC markets were, however, more concentrated, with 4 companies capturing 69% of FDC volume across the ten countries. Among second line drugs, fluoroquinolones were widely available, with significant volumes used for TB in India, Pakistan and Indonesia. However, certain WHO-recommended drugs were not available and in general there were insufficient drug volumes to cover the majority of the expected burden of multidrug-resistant TB (MDR-TB). Private TB drug markets in several HBCs are substantial, stable, and complicated. This calls for appropriate policy and market responses, including expansion of Public-Private Mix (PPM) programs, greater reach, flexibility and appeal of public programs, regulatory and quality enforcement, and expansion of public MDR-TB treatment programs.

  1. Lifestyle Factors in Hypertension Drug Research: Systematic Analysis of Articles in a Leading Cochrane Report

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    Dan E. Wilson

    2014-01-01

    Full Text Available Established standards for first-line hypertension management include lifestyle modification and behavior change. The degree to which and how lifestyle modification is systematically integrated into studies of first-line drug management for hypertension is of methodological and clinical relevance. This study systematically reviewed the methodology of articles from a recent Cochrane review that had been designed to inform first-line medical treatment of hypertension and was representative of high quality established clinical trials in the field. Source articles (n=34 were systematically reviewed for lifestyle interventions including smoking cessation, diet, weight loss, physical activity and exercise, stress reduction, and moderate alcohol consumption. 54% of articles did not mention lifestyle modification; 46% contained nonspecific descriptions of interventions. We contend that hypertension management research trials (including drug studies need to elucidate the benefits and risks of drug-lifestyle interaction, to support the priority of lifestyle modification, and that lifestyle modification, rather than drugs, is seen by patients and the public as a priority for health professionals. The inclusion of lifestyle modification strategies in research designs for hypertension drug trials could enhance current research, from trial efficacy to clinical outcome effectiveness, and align hypertension best practices of a range of health professionals with evidence-based knowledge translation.

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

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    Eva Laker

    2014-11-01

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

  3. Budget impact analysis of first-line treatment with pazopanib for advanced renal cell carcinoma in Spain

    Science.gov (United States)

    2013-01-01

    Background Due to economic constraints, cancer therapies are under close scrutiny by clinicians, pharmacists and payers alike. There is no published pharmacoeconomic evidence guiding the choice of first-line therapy for advanced renal cell carcinoma (RCC) in the Spanish setting. We aimed to develop a model describing the natural history of RCC that can be used in healthcare decision-making. We particularly analyzed the budget impact associated with the introduction of pazopanib compared to sunitinib under the Spanish National Healthcare System (NHS) perspective. Methods We developed a Markov model to estimate the future number of cases of advanced RCC (patients with favorable or intermediate risk) resulting either from initial diagnosis or disease progression after surgery. The model parameters were obtained from the literature. We assumed that patients would receive either pazopanib or sunitinib as first-line therapy until disease progression. Pharmacological costs and costs associated with the management of adverse events (AE) were considered. A univariate sensitivity analysis was undertaken in order to test the robustness of the results. Results The model predicted an adult RCC prevalence of 7.5/100,000 (1-year), 20.7/100,000 (3-year) and 32.5/100,000 (5-year). These figures are very close to GLOBOCAN reported RCC prevalence estimates of 7.6/100,000, 20.2/100,000 and 31.1/100,000, respectively. The model predicts 1,591 advanced RCC patients with favorable or intermediate risk in Spain in 2013. Annual per patient pharmacological costs were €32,365 and €39,232 with pazopanib and sunitinib, respectively. Annual costs associated with the management of AE were €662 and €974, respectively. Overall annual per patient costs were €7,179 (18%) lower with pazopanib compared to sunitinib. For every point increase in the percentage of patients treated with pazopanib, the NHS would save €67,236. If all the 1,591 patients predicted were treated with pazopanib, the

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

    Science.gov (United States)

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

    2016-07-13

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

  5. Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model.

    Science.gov (United States)

    Brunelli, Steven M; Sibbel, Scott P; Van Wyck, David; Sharma, Amit; Hsieh, Andrew; Chertow, Glenn M

    2017-03-01

    Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

  6. Efficacy of caspofungin combined with trimethoprim/sulfamethoxazole as first-line therapy to treat non-HIV patients with severe pneumocystis pneumonia.

    Science.gov (United States)

    Zhang, Gensheng; Chen, Miaomiao; Zhang, Shufang; Zhou, Hongwei; Ji, Xiaozhen; Cai, Jiachang; Lou, Tianzheng; Cui, Wei; Zhang, Ning

    2018-02-01

    Combined treatment with caspofungin and trimethoprim/sulfamethoxazole (TMP/SMZ) as salvage therapy in non-HIV positive patients with severe pneumocystis pneumonia (PCP) yields poor outcomes. It remains unknown whether the use of this combination strategy as a first-line therapy would improve patient outcomes. The present study aimed to assess the efficacy of caspofungin combined with TMP/SMZ as a first-line therapy in non-HIV positive patients with severe PCP. A retrospective cohort study was conducted between March 2016 and February 2017. Patient clinical characteristics and outcomes were compared between two groups receiving first-line and second-line therapy respectively. In addition, similar cases from previous studies were assessed. A total of 14 patients were included in the present study (mean age, 58.79±14.41 years); including 9 patients receiving caspofungin and TMP/SMZ as a first-line therapy and 5 that received it as a second-line therapy. The overall positive response rate was 71.43% (10/14), with 88.89 (8/9) and 40.00% (2/5) in the first-line and second-line therapy groups, respectively (P=0.095). The positive response rates of patients requiring invasive mechanical ventilation differed significantly between the first-line (5/6, 83.33%) and the second-line (0/3, 0%) therapy groups (P=0.048). All-cause hospital mortality was 42.86% (6/14), with mortality rates of 33.33 (3/9) and 60.00% (3/5) in the first-line and second-line therapy groups, respectively (P=0.580). Combined with previously reported cases (n=27), the positive response rate was significantly greater in the first-line therapy group (11/12, 91.67%) than in the second-line therapy group (8/15, 53.33%, P=0.043). No significant differences were in all-cause mortality rates between the two groups (25.00 vs. 46.67%, P=0.424) were identified, despite the fact that all-course mortality in the first-line therapy group was ~50% that of the second-line therapy group. Therefore, the results of the

  7. Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease

    Science.gov (United States)

    Cannas, Giovanna; Poutrel, Solène; Thomas, Xavier

    2017-01-01

    While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome. PMID:28293403

  8. HYDROXYCARBAMINE: FROM AN OLD DRUG USED IN MALIGNANT HEMOPATHIES TO A CURRENT STANDARD IN SICKLE CELL DISEASE

    Directory of Open Access Journals (Sweden)

    Giovanna Cannas

    2017-02-01

    Full Text Available While hydroxycarbamine (hydroxyurea, HU has less and less indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support of safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. HU has become the standard-of-care for sickle cell anemia, but remains underused. Barriers to its use should be identified and overcome.

  9. Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer.

    Science.gov (United States)

    Tiainen, Leena; Tanner, Minna; Lahdenperä, Outi; Vihinen, Pia; Jukkola, Arja; Karihtala, Peeter; Paunu, Niina; Huttunen, Teppo; Kellokumpu-Lehtinen, Pirkko-Liisa

    2016-12-01

    The study evaluated the efficacy of bevacizumab combined with a taxane-based treatment for advanced breast cancer. In this non-randomized phase II study 65 patients received 10 mg/kg bevacizumab i.v. (days 1 and 15, q4w) plus either 50 mg/m2 docetaxel (days 1 and 15, q4w) or 90 mg/m2 paclitaxel (days 1,8 and 15, q4w) i.v. until disease progression, maximal response, unacceptable toxicity or the withdrawal of consent. Patients without progression continued bevacizumab at 15 mg/kg i.v. (q3w) alone, or with endocrine therapy. (NCT00979641). Progression-free survival was 11.3 months (95% confidence interval=9.7-16.0 months) and overall survival was 35.1 months (95% confidence interval=22.2-50.3 months). More than half of the patients (62%) responded at least partially. Bevacizumab-related serious adverse events occurred in 10.8% patients and one patient died because of gastrointestinal perforation. Treating advanced breast cancer with a bevacizumab-containing regimen as the first-line cytotoxic treatment resulted in excellent response rates and long survival. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

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

  11. First-line chemotherapy for metastatic breast cancer in patients ≥75 years: a retrospective single-centre analysis.

    Science.gov (United States)

    Debled, Marc; Madranges, Nicolas; Mertens, Cécile; Durand, Michel; Brouste, Véronique; Brain, Etienne; Mauriac, Louis

    2011-10-01

    Data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) are limited. We performed a 7-year retrospective analysis of MBC patients at our institution receiving first-line chemotherapy aged ≥75 years. Of 117 patients, 103 received monotherapy (67 capecitabine, 29 vinorelbine, 5 docetaxel, 2 liposomal doxorubicin) and 14 received polychemotherapy (12 anthracycline-based, 2 vinorelbine-gemcitabine). Chemotherapy demonstrated acceptable tolerability. Median progression-free survival (PFS) and overall survival (OS) from initiation of chemotherapy were 6.2 months and 13.8 months, respectively. At 2 years, 25% of patients were alive; however, 25% died within 3 months of beginning chemotherapy. Independent prognostic factors for longer PFS were good performance status, absence of visceral disease and capecitabine treatment. Good performance status and lack of visceral disease were also significant for OS. These results suggest that palliative chemotherapy should not be systematically excluded in this setting, but should be carefully discussed as it appears to be feasible with apparent benefit in selected patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  12. Weekly docetaxel and vinorelbine (VIN-DOX) as first line treatment in patients with hormone refractory prostate cancer.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Pizza, Carmine; Autorino, Riccardo; De Laurentiis, Michele; Marano, Ombretta; D'Alessio, Adele; Cancello, Giuseppe; Altieri, Vincenzo; Tortora, Giampaolo; Perdonà, Sisto; Bianco, Angelo Raffaele; De Placido, Sabino

    2004-12-01

    The current study investigated the clinical benefit, the impact on biochemical and objective response and tolerability of weekly docetaxel with vinorelbine (VIN-DOX) in symptomatic patients with hormone refractory prostate cancer (HRPC). Patients were treated with docetaxel 25 mg/m2 and vinorelbine 20 mg/m2, intravenously for 6 consecutive weeks followed by a 2 week rest repeatedly until disease progression. Clinical benefit evaluations, based on Karnofsky performance status (KPS) and pain measure, were assessed weekly during therapy. A clinical benefit response was defined as a sustained (> or =4 weeks) improvements in one of these parameters. Changes in prostate-specific antigen (PSA) levels, tumoral response and toxicity also were evaluated. 19 men (median age 68 years), were treated. Overall, 42% of patients achieved a KPS significant change and positive pain response; 47% achieved a 50% or greater reduction in PSA. The objective response rate was observed in 2 of 9 patients with measurable disease (22%). The most important toxicity was neutropenia (Grade 3 = 32%). The combination of weekly VIN-DOX appears to be feasible. VIN-DOX was found to be associated with improvement in clinical benefit response and biochemical response and well tolerated as first line treatment in HRPC.

  13. Maitake mushroom (Grifola frondosa) extract induces ovulation in patients with polycystic ovary syndrome: a possible monotherapy and a combination therapy after failure with first-line clomiphene citrate.

    Science.gov (United States)

    Chen, Jui-Tung; Tominaga, Kunihiko; Sato, Yoshiaki; Anzai, Hideo; Matsuoka, Ryo

    2010-12-01

    Insulin resistance is a prominent feature of polycystic ovary syndrome (PCOS), and insulin-sensitizing drugs are used to induce ovulation. Recently, it was reported that an extract from Maitake mushroom (Grifola frondosa) improves insulin resistance. The objective was to explore the effects of Maitake extract (SX-fraction: MSX) to induce ovulation in patients with PCOS in comparison with and in combination with clomiphene citrate (CC). We conducted an open trial with 80 patients with PCOS at three clinics in Japan. Seventy-two (72) new patients were randomly assigned to receive MSX or CC monotherapy for up to 12 weeks. Eighteen (18) patients who did not respond to MSX or CC were subjected to combination therapy of MSX and CC for up to 16 weeks. Eight (8) patients with documented history of failure to CC received combination therapy from the beginning. Ovulation was assessed by ultrasonography. Twenty-six (26) patients in the MSX group and 31 in the CC group were evaluated for ovulation. The ovulation rates for MSX and CC were as follows: 76.9% (20/26) and 93.5% (29/31), respectively by the patients (NS), and 41.7% (30/72) and 69.9% (58/83), respectively, by the cycles (p = 0.0006). In the combination therapy, 7 of 7 patients who failed in MSX monotherapy and 6 of 8 patients who failed in CC monotherapy showed ovulation. The present study suggests that MSX alone may induce ovulation in PCOS patients and may be useful as an adjunct therapy for patients who failed first-line CC treatment.

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

    Directory of Open Access Journals (Sweden)

    Ducray François

    2010-09-01

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

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

    DEFF Research Database (Denmark)

    Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima

    2008-01-01

    BACKGROUND: In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin...... Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here...... investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the Plasmodium falciparum genes Pfdhfr, Pfdhps and Pfcrt before and a year after the introduction of SP. METHODS: Samples were collected during two cross sectional surveys in early 2002 and 2003...

  16. HIV2EU: supporting standardized HIV-2 drug resistance interpretation in Europe

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    F Brun-Vezinet

    2012-11-01

    Full Text Available Various items are complicating the treatment of HIV-2 infected patients. Compared to HIV-1 there is much less treatment experience, no evidence from randomized control trials, a reduced number of effective drugs and no broadly available test for viral load monitoring. In case of treatment failure there is only limited guidance and presently no easy accessible tool for nucleic acid sequence interpretation available. To solve this problem, we initiated an expert workshop to address some of these problems. A panel of experts from four different European countries voted on a rule set for interpretation of mutations in the HIV-2 protease, reverse transcriptase and integrase. Rules were proposed by each member and were then modified during discussion by considering data gained from HIV-1 and accumulated experience of the follow up of HIV-2-infected patients. Based on the HIV-GRADE internet-tool an online tool was developed to make the rule set easily accessible and usable. Rules were laid down for the interpretation of HIV-2 drug resistance to NRTIs, PIs and INIs (integrase inhibitors. Due to natural resistance of HIV-2, usage of NNRTIs and T-20 was not recommended as part of an antiretroviral regimen for HIV-2. These rules were then translated in a machine interpretable format (algorithm specification interface, ASI and the HIV-GRADE tool was extended for usage of HIV-2 sequences. Further consensus sequences were generated from the reference sequence data set provided by Los Alamos National Laboratories. In contrast to HIV-1, mutations were compared to a group specific consensus sequence (Group A or Group B and not to a consensus sequence from the most predominant HIV-2 Group A. This change was necessary due to significant differences between the various HIV-2 strains. We developed a rule set and an automated tool for HIV-2 drug resistance analyses. This tool and the rules will be freely available on the internet. Access to the pre

  17. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    du Bois, Andreas; Herrstedt, Jørn; Hardy-Bessard, Anne-Claire

    2010-01-01

    One attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug....

  18. HPLC Fingerprinting of Sennosides in Laxative Drugs with Isolation of Standard Substances from Some Senna Leaves

    Directory of Open Access Journals (Sweden)

    L. Omur Demirezer

    2011-01-01

    Full Text Available Senna leaves are one of the oldest medicinal herbs and they are used as laxative. Herbal teas which contain senna leaves are most commonly used to promote weight loss. The quality control of slimming teas which contain Senna leaves and also pharmaceutical preparations including Senna extract enriched by sennoside B was achieved by HPLC fingerprinting method. While the presence of sennoside A and B in laxative drugs was proved, it was seen to be devoid of sennosides in slimming teas. Kaempferol 3-O-β-D-gentiobioside (1, aloe-emodine 8-O-β-D-glucopyranoside (2, rhein 8-O-β-D-glucopyranoside (3, torachrysone 8-O-β-D-glucopyranoside (4, isorhamnetine 3-O-β-D-gentiobioside (5 were also isolated from Senna leaves.

  19. Thoughtflow: Standards and Tools for Provenance Capture and Workflow Definition to Support Model-Informed Drug Discovery and Development.

    Science.gov (United States)

    Wilkins, J J; Chan, Pls; Chard, J; Smith, G; Smith, M K; Beer, M; Dunn, A; Flandorfer, C; Franklin, C; Gomeni, R; Harnisch, L; Kaye, R; Moodie, S; Sardu, M L; Wang, E; Watson, E; Wolstencroft, K; Cheung, Sya

    2017-05-01

    Pharmacometric analyses are complex and multifactorial. It is essential to check, track, and document the vast amounts of data and metadata that are generated during these analyses (and the relationships between them) in order to comply with regulations, support quality control, auditing, and reporting. It is, however, challenging, tedious, error-prone, and time-consuming, and diverts pharmacometricians from the more useful business of doing science. Automating this process would save time, reduce transcriptional errors, support the retention and transfer of knowledge, encourage good practice, and help ensure that pharmacometric analyses appropriately impact decisions. The ability to document, communicate, and reconstruct a complete pharmacometric analysis using an open standard would have considerable benefits. In this article, the Innovative Medicines Initiative (IMI) Drug Disease Model Resources (DDMoRe) consortium proposes a set of standards to facilitate the capture, storage, and reporting of knowledge (including assumptions and decisions) in the context of model-informed drug discovery and development (MID3), as well as to support reproducibility: "Thoughtflow." A prototype software implementation is provided. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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

    Science.gov (United States)

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

    2017-05-01

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

  1. Preparation and characterization of standardized pomegranate extract-phospholipid complex as an effective drug delivery tool

    Directory of Open Access Journals (Sweden)

    Amisha Kamlesh Vora

    2015-01-01

    Full Text Available Punicalagins, a pair of anomeric ellagitannins, present in Punica granatum (Pomegranates are known to possess excellent antioxidant activity in vitro, but poor oral bioavailability. The reasons cited for poor bioavailability are their large molecular size, poor lipophilicity, and degradation by colonic microflora into less active metabolites. The objective of the present research work was to complex the standardized pomegranate extract (SPE with phospholipid to formulate standardized pomegranate extract-phospholipid complex (SPEPC, characterize it and check its permeability through an ex vivo everted gut sac experiment. SPEPC was prepared by mixing SPE (30% punicalagins and soya phosphatidylcholine (PC in 1:1 v/v mixture of methanol and dioxane and spray-drying the mixture. The complex was characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. It was evaluated for its octanol solubility, dissolution, and permeability by everted the gut sac technique. The characterization methods confirmed the formation of complex. Increased n-octanol solubility of the complex proved its increased lipophilicity. Dissolution studies revealed that the phospholipid covering may prevent the punicalagins to be released in gastro-intestinal tract, thus preventing their colonic microbial degradation. SPEPC showed better apparent permeability than SPE in an everted gut sac technique. Hence, it could be concluded that phospholipid complex of SPE may be of potential use in increasing the permeability and hence the bioavailability of punicalagins.

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

    Science.gov (United States)

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

    2017-09-01

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

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

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    Shu Yong-Qian

    2010-09-01

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

  4. Association between molecular monitoring and long-term outcomes in chronic myelogenous leukemia patients treated with first line imatinib.

    Science.gov (United States)

    Goldberg, Stuart L; Chen, Lei; Guerin, Annie; Macalalad, Alexander R; Liu, Nathan; Kaminsky, Michael; Ericson, Solveig G; Wu, Eric Q

    2013-09-01

    Molecular monitoring using quantitative polymerase chain reaction (qPCR) of BCR-ABL mRNA transcripts using the international scale (IS) is recommended by the National Comprehensive Cancer Network and the European LeukemiaNet for patients with chronic myelogenous leukemia in chronic phase (CML-CP). This study assessed the impact of the frequency of qPCR testing on progression-free survival (PFS). This retrospective chart review of 402 CML-CP patients on first line imatinib therapy, performed by 38 community-based US physicians, analyzed the impact of the frequency of molecular monitoring on the risk of progression and PFS. Time to progression and progression-free survival. Over the 3 year study, 13.2% of patients did not have any qPCR monitoring and 46.3% had 3-4 qPCR tests per year; 5.7% of CML-CP patients progressed to accelerated/blast phase or died. Compared to patients with no qPCR monitoring, those with 3-4 qPCR tests per year had a lower risk of progression (HR = 0.085; p = 0.001) and longer PFS (HR = 0.088; p = 0.001) after adjusting for potential confounders, as did those patients with 1-2 qPCR tests per year (both p < 0.02). Results were consistent after adjusting for Sokal score when available. This is the first study to document the clinical impact of frequent molecular monitoring, and the findings underscore the importance of regular molecular monitoring in delivering quality care for CML. These findings could be subject to unobserved confounders.

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

    Science.gov (United States)

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

    2017-11-01

    Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 109/L (OR 7.64, P mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 109/L (OR 2.65, P mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

  6. Polymorphism of TS 3'-UTR predicts survival of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.

    Science.gov (United States)

    Gao, J; He, Q; Hua, D; Mao, Y; Li, Y; Shen, L

    2013-08-01

    Capecitabine-containing chemotherapy was widely used in clinic medication. We investigated the association of the thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase (DPD) polymorphisms with the clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Blood samples were collected prior to treatment from 125 patients with advanced gastric cancer and the TS (two or three repeats of a 28 bp sequence in 5'-untranslated region and 6 bp insertion or deletion in 3'-untranslated region), MTHFR (C677T) and DPD (IVS14+1G > A) polymorphisms were determined using PCR amplification and Sanger sequencing. The median age of 125 patients was 58 years (range, 23-76) with female 42 and male 83, and the response rate, median progression-free survival and overall survival (OS) were 43.2 %, 5.2 and 11.0 months. The median OS in patients with TS ins6/ins6 genotype (6.8 months) was significantly shorter than those in patients with ins6/del6 (11.0 months, P = 0.016) and del6/del6 (11.5 months, P = 0.039) genotypes. Cox multivariate analysis also showed that TS ins6/ins6 genotype was the independent poor OS predictor (P = 0.001, HR = 3.182). No significant associations were found between the polymorphisms of TS 5'-UTR/MTHFR and clinical outcome, and no IVS14+1G > A polymorphism of DPD was found in this study. We first reported that TS 3'-UTR ins6/ins6 genotype could predict the poor survival of advanced gastric cancer patients treated with capecitabine plus paclitaxel, which would be further verified in a large multicenter study.

  7. Between being and doing - the nature of leadership of first-line nurse managers and registered nurses.

    Science.gov (United States)

    Johansson, Gunilla; Andersson, Lars; Gustafsson, Barbro; Sandahl, Christer

    2010-09-01

    The aim of this study was to describe first-line nurse managers' (F-LNMs) and subordinate registered nurses' (RNs) conceptions and experiences of their routine work and how leadership was exercised. Extensive changes in health care organisations have had a powerful impact on leadership in nursing management. Nursing leadership, in turn, has an affect on both the quality of care and the subordinates' work environment. Therefore, it is important to enhance our understanding of current leadership in nursing management. This is a descriptive qualitative study carried out in three units at three Swedish hospitals. Three F-LNMs and 14 RNs participated. Interviews were used to collect data. The interviews were analysed using qualitative content analysis. The result of this study was illustrated in one main theme referred to in this study as between being and doing. The RNs and F-LNMs described what it was to be a good professional (being), how they were engaged in creating a good work climate (doing) and personal outcomes of this project (gaining). The reciprocal relation between being and doing, which can be described as the development of virtues, was a central point in the professional work of the F-LNMs and RNs. The development of virtues is also a strategy to attain the goals of nursing and establish a work climate that motivates staff and improves performance. RELEVANCE TO CLINICAL PRACTICES: The implication for nursing management is to create ample space to develop strategies and knowledge about how leadership in nursing management can stimulate the development of a common perspective of good care and professional virtues appropriate for health care praxis. © 2010 Blackwell Publishing Ltd.

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

    Science.gov (United States)

    Lambert-Niclot, S; George, E C; Pozniak, A; White, E; Schwimmer, C; Jessen, H; Johnson, M; Dunn, D; Perno, C F; Clotet, B; Plettenberg, A; Blaxhult, A; Palmisano, L; Wittkop, L; Calvez, V; Marcelin, A G; Raffi, F

    2016-04-01

    To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial.

    Science.gov (United States)

    Chiba, Mitsuro; Tsuji, Tsuyotoshi; Nakane, Kunio; Tsuda, Satoko; Ishii, Hajime; Ohno, Hideo; Watanabe, Kenta; Ito, Mai; Komatsu, Masafumi; Sugawara, Takeshi

    2017-01-01

    Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naïve to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. IPF therapy can induce remission in most patients with CD who are naïve to biologics regardless of age or whether they have a new diagnosis or relapse.

  10. The evidence base for efficacy of the low FODMAP diet in irritable bowel syndrome: is it ready for prime time as a first-line therapy?

    Science.gov (United States)

    Gibson, Peter R

    2017-03-01

    Six randomized controlled trials comparing low FODMAP diet with placebo approaches have all indicated efficacy in patients with irritable bowel syndrome (IBS). The studies have provided all the food (n = 3) or utilized dietitian-led education (n = 3). They have variably met criticisms regarding issues such as the choice of placebo, the number of patients studied, the success of blinding, and the duration of the interventions, but the results are uniformly positive for the diet. Real-world experience of the low FODMAP diet has confirmed the findings of the randomized studies, in that about 70% of patients respond. Difficulty in delivering the diet has not been an issue, and the majority of patients find the diet easy to follow when dietitian led. Observational studies have suggested durability of efficacy, even in association with reintroduction of FODMAPs as recommended. Three studies comparing institution of standard dietary guidelines for IBS with the low FODMAP diet have found either similar or improved outcomes with the latter. Low FODMAP diet also has similar efficacy to that of gut-directed hypnotherapy, another strategy with broad benefit in IBS. There are currently no clinically applicable indices that predict response to the diet. In conclusion, clinical trials and observational studies support the notion that a dietitian-led low FODMAP diet is ready for primetime and should be considered as a first-line therapy for patients with IBS where the use of a restrictive diet is appropriate. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  11. Increased resistance to first-line agents among bacterial pathogens isolated from urinary tract infections in Latin America: time for local guidelines?

    Directory of Open Access Journals (Sweden)

    Soraya S Andrade

    2006-11-01

    Full Text Available Emerging resistance phenotypes and antimicrobial resistance rates among pathogens recovered from community-acquired urinary tract infections (CA-UTI is an increasing problem in specific regions, limiting therapeutic options. As part of the SENTRY Antimicrobial Surveillance Program, a total of 611 isolates were collected in 2003 from patients with CA-UTI presenting at Latin American medical centers. Each strain was tested in a central laboratory using Clinical Laboratory Standard Institute (CLSI broth microdilution methods with appropriate controls. Escherichia coli was the leading pathogen (66%, followed by Klebsiella spp. (7%, Proteus mirabilis (6.4%, Enterococcus spp. (5.6%, and Pseudomonas aeruginosa (4.6%. Surprisingly high resistance rates were recorded for E. coli against first-line orally administered agents for CA-UTI, such as ampicillin (53.6%, TMP/SMX (40.4%, ciprofloxacin (21.6%, and gatifloxacin (17.1%. Decreased susceptibility rates to TMP/SMX and ciprofloxacin were also documented for Klebsiella spp. (79.1 and 81.4%, respectively, and P. mirabilis (71.8 and 84.6%, respectively. For Enterococcus spp., susceptibility rates to ampicillin, chloramphenicol, ciprofloxacin, and vancomycin were 88.2, 85.3, 55.9, and 97.1%, respectively. High-level resistance to gentamicin was detected in 24% of Enterococcus spp. Bacteria isolated from patients with CA-UTI in Latin America showed limited susceptibility to orally administered antimicrobials, especially for TMP/SMX and fluoroquinolones. Our results highlight the need for developing specific CA-UTI guidelines in geographic regions where elevated resistance to new and old compounds may influence prescribing decisions.

  12. Clinical Impact of the Number of Treatment Cycles in First-Line Docetaxel for Patients With Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette; Sengeløv, Lisa

    2017-04-01

    We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. Charts from 421 consecutive patients who initiated standard treatment with docetaxel-based chemotherapy (75 mg/m 2 every 3 weeks) between 2007 and 2013 were reviewed. Patients who received patients were divided into 2 groups on the basis of whether or not ≥ 9 cycles of docetaxel were administered (n = 108 and 184, respectively). Reasons for treatment discontinuation and postdocetaxel treatments were registered. Prostate-specific antigen (PSA) responses were defined as a confirmed ≥ 50% decrease in baseline PSA levels. Overall survival (OS) was calculated from start of therapy using the Kaplan-Meier method. Cox proportional hazards were calculated to estimate the effect of clinical variables on OS. OS was longer in patients treated with ≥ 9 cycles of docetaxel (21.9 months vs. 17.2 months; P patients treated with ≥ 9 cycles of docetaxel when only patients ending docetaxel because of toxicity or treatment conclusion (22.3 vs. 19.4 months; P = .048, log rank) or patients who achieved a PSA response (22.3 vs. 18.7 months; P = .012, log rank) were evaluated. mCRPC-related prognostic factors and patients who received ≥ 1 subsequent line of therapy post-docetaxel were well balanced. On the basis of our retrospective findings, a superior OS was found in patients treated with ≥ 9 cycles of docetaxel when adjusting for known prognostic factors. Dose reductions might increase the number of docetaxel cycles administered. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Induction with Infliximab and a Plant-Based Diet as First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial

    Science.gov (United States)

    Chiba, Mitsuro; Tsuji, Tsuyotoshi; Nakane, Kunio; Tsuda, Satoko; Ishii, Hajime; Ohno, Hideo; Watanabe, Kenta; Ito, Mai; Komatsu, Masafumi; Sugawara, Takeshi

    2017-01-01

    Background Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. Objective To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. Methods This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naïve to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. Results Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. Conclusion IPF therapy can induce remission in most patients with CD who are naïve to biologics regardless of age or whether they have a new diagnosis or relapse. PMID:29035182

  14. Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities.

    Science.gov (United States)

    Fiorentino, Francesco; Napoletano, Stefania; Caiazzo, Fiorina; Sessa, Mariateresa; Bono, Sara; Spizzichino, Letizia; Gordon, Anthony; Nuccitelli, Andrea; Rizzo, Giuseppe; Baldi, Marina

    2013-07-01

    In this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors.

  15. A single center experience: rituximab plus cladribine is an effective and safe first-line therapy for unresectable bronchial-associated lymphoid tissue lymphoma.

    Science.gov (United States)

    Wei, Zheng; Li, Jing; Cheng, Zhixiang; Yuan, Ling; Liu, Peng

    2017-04-01

    Bronchial-associated lymphoid tissue (BALT) lymphoma is a relatively rare form of B-cell non-Hodgkin lymphoma (B-NHL). To date, the standard systemic treatment for this disease is still under debate, and few data are accessible for newly diagnosed unresectable BALT lymphoma presented with advanced disease. The combination of rituximab (R) and cladribine (2-CdA) has shown some activity in indolent B-NHL, but its usage has not been tested in disseminated BALT lymphoma so far. An observational retrospective study was performed on homogeneous data of 8 patients with biopsy-proven stage IV BALT lymphoma to assess the efficacy and the safety of R-2-CdA therapy. All but one of the patients received six courses of R-2-CdA regimen consisted of rituximab 375 mg/m2 IV day 1 and cladribine 0.1 mg/kg IV days 1-4 every 21 days; one patient completed 4 cycles and received additional R maintenance. A high overall response rate (ORR) was observed (100%), with 2 patients (25%) achieved a complete remission (CR), the remaining (75%) a partial response. Improvement of pulmonary function was observed in all tested patients. Grade 3 and 4 toxicities were leukocytopenia and neutropenia in 3 patients (37.5%), diarrhea in one (12.5%). Estimated two-year progression-free survival (PFS) and 2-yr overall survival (OS) were 80.0% (95% CI, 20.3-96.7%) and 100%, respectively. R-2-CdA therapy demonstrated high activity and tolerable toxicity in chemotherapy-naïve patients with unresectable BALT lymphoma of advanced stage. Although further large-scale study is needed for consolidation, R-2-CdA regimen could be a good first-line therapy option for patients with unresectable BALT lymphoma.

  16. First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients with advanced gastric cancer: a multicenter propensity score matched study.

    Science.gov (United States)

    Makiyama, Akitaka; Kunieda, Kenji; Noguchi, Masaaki; Kajiwara, Takeshi; Tamura, Takao; Takeda, Koji; Sugiyama, Junko; Minashi, Keiko; Moriwaki, Toshikazu; Sugimoto, Naotoshi; Nagase, Michitaka; Negoro, Yuji; Tsuda, Takashi; Shimodaira, Hideki; Okano, Naohiro; Tsuji, Akihito; Sakai, Daisuke; Yanagihara, Kazuhiro; Ueda, Shinya; Tamura, Shingo; Otsu, Satoshi; Honda, Takuya; Matsushita, Yuzo; Okuno, Tatsuya; Kashiwada, Tomomi; Nozaki, Akira; Ebi, Masahide; Okuda, Hiroyuki; Shimokawa, Mototsugu; Hironaka, Shuichi; Hyodo, Ichinosuke; Baba, Eishi; Boku, Narikazu; Muro, Kei; Esaki, Taito

    2018-01-20

    Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p S-1 in elderly patients with AGC. We are now conducting a prospective comparative study to optimize treatment strategy and explore applicability of the geriatric assessment for these patients.

  17. Unexplained developmental delay/learning disability: guidelines for best practice protocol for first line assessment and genetic/metabolic/radiological investigations.

    Science.gov (United States)

    O'Byrne, J J; Lynch, S A; Treacy, E P; King, M D; Betts, D R; Mayne, P D; Sharif, F

    2016-02-01

    Investigation of patients, particularly children, with unexplained global developmental delay (GDD)/learning disability (LD) has been challenging due to a lack of clear guidance from specialised centres. Limited knowledge of rare diseases and a poor understanding of the purpose or limitations of appropriate investigations have been some of the principal reasons for this difficulty. A guideline development group was formed to recommend on appropriate, first line metabolic, genetic and radiological investigations for children and adults with unexplained GDD/ID. A comprehensive literature search was conducted, evaluated and reviewed by the guideline committee and a best practice protocol for first line assessment and genetic, metabolic and radiological investigations was decided upon after considering diagnostic yield, practicality, treatability and costs. It is hoped that these recommendations will become national guidelines for the first line metabolic, genetic and radiological investigation of patients presenting with unexplained GDD/ID.

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

    Science.gov (United States)

    Princeton, J C; Gaspar, T M

    1991-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  20. Multicenter phase II study of capecitabine plus cisplatin as first-line therapy for human epidermal growth factor receptor 2-negative advanced gastric cancer: Yokohama Clinical Oncology Group Study YCOG1107.

    Science.gov (United States)

    Sato, Kei; Kunisaki, Chikara; Kosaka, Takashi; Takagawa, Ryo; Takahashi, Masazumi; Izumisawa, Yusuke; Miyamoto, Hiroshi; Sato, Sho; Tanaka, Yusaku; Yamaguchi, Naotaka; Kimura, Jun; Ono, Hidetaka A; Makino, Hirochika; Akiyama, Hirotoshi; Endo, Itaru

    2017-11-01

    S-1 plus cisplatin therapy is the recommended standard first-line regimen for human epidermal growth factor receptor 2 (HER-2)-negative advanced unresectable or recurrent gastric cancer (AGC) in the Japanese Gastric Cancer Treatment Guidelines. By contrast, capecitabine plus cisplatin (XP) therapy has been second-line therapy for these patients. This prospective study aimed to evaluate the efficacy and safety of XP as a first-line regimen for HER2-negative patients with AGC. In this multicenter, open-label, phase II study, patients received cisplatin (80 mg/m2 i.v. day 1) plus capecitabine (1000 mg/m2 orally, twice daily, days 1-14) at 3 week intervals until disease progression or non-continuation for various reasons. The primary endpoint was overall response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profiles. Thirty-six patients with HER2-negative AGC were enrolled in this study. Of these, 16 patients with evaluable lesions were assessable for efficacy and 36 were assessable for toxicity. One patient achieved a complete response and five partial responses. The overall response rate was 37.5% [95% confidence interval (CI) 13.7-61.2%] calculated on an intention-to-treat basis. The median PFS and median OS were 5.2 months (95% CI 4.2-6.2 months) and 16.9 months (95% CI 5.8-27.9 months), respectively. Treatment-related adverse events were generally mild; the most common grade 3/4 adverse event was neutropenia (27.8%), followed by anorexia (19.4%), leucopenia (16.7%), anemia (16.7%), and nausea (13.9%). XP as first-line therapy is effective and well tolerated by patients with HER2-negative AGC.

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

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2012-01-01

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

  2. The effectiveness of the McKenzie method in addition to first-line care for acute low back pain: a randomized controlled trial.

    Science.gov (United States)

    Machado, Luciana A C; Maher, Chris G; Herbert, Rob D; Clare, Helen; McAuley, James H

    2010-01-26

    Low back pain is a highly prevalent and disabling condition worldwide. Clinical guidelines for the management of patients with acute low back pain recommend first-line treatment consisting of advice, reassurance and simple analgesics. Exercise is also commonly prescribed to these patients. The primary aim of this study was to evaluate the short-term effect of adding the McKenzie method to the first-line care of patients with acute low back pain. A multi-centre randomized controlled trial with a 3-month follow-up was conducted between September 2005 and June 2008. Patients seeking care for acute non-specific low back pain from primary care medical practices were screened. Eligible participants were assigned to receive a treatment programme based on the McKenzie method and first-line care (advice, reassurance and time-contingent acetaminophen) or first-line care alone, for 3 weeks. Primary outcome measures included pain (0-10 Numeric Rating Scale) over the first seven days, pain at 1 week, pain at 3 weeks and global perceived effect (-5 to 5 scale) at 3 weeks. Treatment effects were estimated using linear mixed models. One hundred and forty-eight participants were randomized into study groups, of whom 138 (93%) completed the last follow-up. The addition of the McKenzie method to first-line care produced statistically significant but small reductions in pain when compared to first-line care alone: mean of -0.4 points (95% confidence interval, -0.8 to -0.1) at 1 week, -0.7 points (95% confidence interval, -1.2 to -0.1) at 3 weeks, and -0.3 points (95% confidence interval, -0.5 to -0.0) over the first 7 days. Patients receiving the McKenzie method did not show additional effects on global perceived effect, disability, function or on the risk of persistent symptoms. These patients sought less additional health care than those receiving only first-line care (P = 0.002). When added to the currently recommended first-line care of acute low back pain, a treatment programme

  3. The effectiveness of the McKenzie method in addition to first-line care for acute low back pain: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Herbert Rob D

    2010-01-01

    Full Text Available Abstract Background Low back pain is a highly prevalent and disabling condition worldwide. Clinical guidelines for the management of patients with acute low back pain recommend first-line treatment consisting of advice, reassurance and simple analgesics. Exercise is also commonly prescribed to these patients. The primary aim of this study was to evaluate the short-term effect of adding the McKenzie method to the first-line care of patients with acute low back pain. Methods A multi-centre randomized controlled trial with a 3-month follow-up was conducted between September 2005 and June 2008. Patients seeking care for acute non-specific low back pain from primary care medical practices were screened. Eligible participants were assigned to receive a treatment programme based on the McKenzie method and first-line care (advice, reassurance and time-contingent acetaminophen or first-line care alone, for 3 weeks. Primary outcome measures included pain (0-10 Numeric Rating Scale over the first seven days, pain at 1 week, pain at 3 weeks and global perceived effect (-5 to 5 scale at 3 weeks. Treatment effects were estimated using linear mixed models. Results One hundred and forty-eight participants were randomized into study groups, of whom 138 (93% completed the last follow-up. The addition of the McKenzie method to first-line care produced statistically significant but small reductions in pain when compared to first-line care alone: mean of -0.4 points (95% confidence interval, -0.8 to -0.1 at 1 week, -0.7 points (95% confidence interval, -1.2 to -0.1 at 3 weeks, and -0.3 points (95% confidence interval, -0.5 to -0.0 over the first 7 days. Patients receiving the McKenzie method did not show additional effects on global perceived effect, disability, function or on the risk of persistent symptoms. These patients sought less additional health care than those receiving only first-line care (P = 0.002. Conclusions When added to the currently recommended

  4. First-line antiretroviral therapy after single-dose nevirapine exposure in South Africa: a cost-effectiveness analysis of the OCTANE trial.

    Science.gov (United States)

    Ciaranello, Andrea L; Lockman, Shahin; Freedberg, Kenneth A; Hughes, Michael; Chu, Jennifer; Currier, Judith; Wood, Robin; Holmes, Charles B; Pillay, Sandy; Conradie, Francesca; McIntyre, James; Losina, Elena; Walensky, Rochelle P

    2011-02-20

    The OCTANE trial reports superior outcomes of lopinavir/ritonavir vs. nevirapine-based antiretroviral therapy (ART) among women previously exposed to single-dose nevirapine to prevent mother-to-child HIV transmission. However, lopinavir/ritonavir is 12 times costlier than nevirapine. We used a computer model, with OCTANE and local data, to simulate HIV-infected, single-dose nevirapine-exposed women in South Africa. Outcomes of three alternative ART sequences were projected: no ART (for comparison), first-line nevirapine, and first-line lopinavir/ritonavir. OCTANE data included mean age (31 years) and CD4 cell count (135/μl); median time since single-dose nevirapine (17 months); and 24-week viral suppression efficacy for first-line ART (nevirapine: 85%, lopinavir/ritonavir: 97%). Outcomes included life expectancy, per-person costs (2008 US$), and incremental cost-effectiveness ratios. With no ART, projected life expectancy was 1.6 years and per-person cost was $2980. First-line nevirapine increased life expectancy (15.2 years) and cost ($13 990; cost-effectiveness ratio: $810/year of life saved versus no ART). First-line lopinavir/ritonavir further increased life expectancy to 16.3 years and cost to $15 630 (cost-effectiveness ratio: $1520/year of life saved versus first-line nevirapine). First-line lopinavir/ritonavir cost-effectiveness was sensitive to prevalence of nevirapine-resistant virus at ART initiation, time from single-dose nevirapine exposure to ART initiation (6-12, 12-24, or >24 months), second-line ART efficacies, and outcomes after 24 weeks on ART. First-line lopinavir/ritonavir-based ART is very cost-effective in single-dose nevirapine-exposed, South African women similar to OCTANE participants. Lopinavir/ritonavir should be initiated in women with known nevirapine resistance or single-dose nevirapine exposure less than 12 months prior, or in whom such information is unknown.

  5. Immunologic and virologic failure after first-line NNRTI-based antiretroviral therapy in Thai HIV-infected children

    Directory of Open Access Journals (Sweden)

    Phasomsap Chayapa

    2011-10-01

    Full Text Available Abstract Background There are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI-based highly active antiretroviral therapy (HAART. We examined the incidence rate of immunologic failure (IF and virologic failure (VF and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART. Methods Antiretroviral (ART-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF. Results 107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR age 6.2 (4.2-8.9 years, CD4% 7 (3-15, HIV-RNA 5.0 (4.9-5.5 log10copies/ml. Nevirapine (NVP and efavirenz (EFV-based HAART were started in 70% and 30%, respectively. At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014, height for age z-score, hemoglobin, and CD4 were seen (all p 10copies/ml. Thirty five (32.7% children experienced VF within 96 weeks. Of these, 24 (68.6% and 31 (88.6% children had VF in the first 24 and 48 weeks respectively. Only 1 (0.9% child experienced IF within 96 weeks and the sensitivity (95%CI of IF to VF was 4 (0.1-20.4% and specificity was 100 (93.9-100%. Conclusion Immunologic failure, as defined here, had low sensitivity compared to VF and

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

    Directory of Open Access Journals (Sweden)

    Shi Y

    2013-05-01

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

  7. Randomized Clinical Trial: Esomeprazole, Bismuth, Levofloxacin, and Amoxicillin or Cefuroxime as First-Line Eradication Regimens for Helicobacter pylori Infection.

    Science.gov (United States)

    Fu, Wei; Song, Zhiqiang; Zhou, Liya; Xue, Yan; Ding, Yu; Suo, Baojun; Tian, Xueli; Wang, Li

    2017-06-01

    The eradication of Helicobacter pylori infection remains a challenge, especially in the patients unsuitable to take penicillin. Cephalosporin has the potential to replace amoxicillin for H. pylori eradication. To compare the effectiveness, safety, and compliance of amoxicillin- and cefuroxime-containing quadruple regimens in treatment-naïve patients. In this open-label randomized control study, 400 patients with H. pylori infection were divided into amoxicillin-containing (esomeprazole 20 mg twice/day, amoxicillin 1000 mg twice/day, levofloxacin 500 mg once/day, and bismuth 220 mg twice/day for 14 days) or cefuroxime-containing (esomeprazole 20 mg twice/day, cefuroxime 500 mg twice/day, levofloxacin 500 mg once/day, and bismuth 220 mg twice/day for 14 days) quadruple therapy groups. The safety and compliance were assessed 1-3 days after eradication. Urea breath test was performed 8-12 weeks after eradication to determine treatment outcome. The baseline data including antibiotic resistance were well matched between the two groups. The eradication rates between amoxicillin- and cefuroxime-containing quadruple therapy groups were not significantly different [intention-to-treat analysis: 83.5% (95% confidence interval 78.3-88.7%) vs. 81.0% (75.5-86.5%), P = 0.513; modified intention-to-treat analysis: 90.3% (86.0-94.6%) vs. 88.5% (83.9-93.2%), P = 0.586; per-protocol analysis: 91.6% (87.5-95.7%) vs. 89.8% (85.3-94.3%), P = 0.560]. The incidence of adverse effects (18.4 vs. 20.1%, P = 0.678) and compliance (94.7 vs. 94.2%, P = 0.813) were also similar. Variate analyses showed that antibiotic resistance and poor compliance were the independent risk factors for eradication failure. Esomeprazole, bismuth, levofloxacin, and amoxicillin or cefuroxime achieved similar and relatively satisfactory cure rates, safety, and compliance in first-line H. pylori eradication. Cefuroxime may be a good alternative medicine for eradication instead of amoxicillin for

  8. DNA damage repair and survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy.

    Science.gov (United States)

    Ronchetti, Livia; Melucci, Elisa; De Nicola, Francesca; Goeman, Frauke; Casini, Beatrice; Sperati, Francesca; Pallocca, Matteo; Terrenato, Irene; Pizzuti, Laura; Vici, Patrizia; Sergi, Domenico; Di Lauro, Luigi; Amoreo, Carla Azzurra; Gallo, Enzo; Diodoro, Maria Grazia; Pescarmona, Edoardo; Vitale, Ilio; Barba, Maddalena; Buglioni, Simonetta; Mottolese, Marcella; Fanciulli, Maurizio; De Maria, Ruggero; Maugeri-Saccà, Marcello

    2017-06-01

    The DNA damage response (DDR) network is exploited by cancer cells to withstand chemotherapy. Gastric cancer (GC) carries deregulation of the DDR and harbors genetic defects that fuel its activation. The ATM-Chk2 and ATR-Chk1-Wee1 axes are deputed to initiate DNA repair. Overactivation of these pathways in cancer cells may represent an adaptive response for compensating genetic defects deregulating G1 -S transition (e.g., TP53) and ATM/ATR-initiated DNA repair (e.g., ARID1A). We hypothesized that DDR-linked biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. Immunohistochemical assessment of DDR kinases (pATM, pChk2, pChk1 and pWee1) and DNA damage markers (γ-H2AX and pRPA32) was performed in biological samples from 110 advanced GC patients treated with first-line chemotherapy, either in phase II trials or in routine clinical practice. In 90 patients, this characterization was integrated with targeted ultra-deep sequencing for evaluating the mutational status of TP53 and ARID1A. We recorded a positive association between the investigated biomarkers. The combination of two biomarkers (γ-H2AX(high) /pATM(high) ) was an adverse factor for both progression-free survival (multivariate Cox: HR 2.23, 95%CI: 1.47-3.40) and overall survival (multivariate Cox: HR: 2.07, 95%CI: 1.20-3.58). The relationship between the γ-H2AX(high) /pATM(high) model and progression-free survival was consistent across the different TP53 backgrounds and was maintained in the ARID1A wild-type setting. Conversely, this association was no longer observed in an ARID1A-mutated subgroup. The γ-H2AX(high) /pATM(high) model negatively impacted survival outcomes in GC patients treated with chemotherapy. The mutational status of ARID1A, but apparently not TP53 mutations, affects its predictive significance. © 2017 UICC.

  9. Is Nonoperative Management the Best First-line Option for High-grade Renal trauma? A Systematic Review.

    Science.gov (United States)

    Sujenthiran, Arunan; Elshout, Pieter Jan; Veskimae, Erik; MacLennan, Steven; Yuan, Yuhong; Serafetinidis, Efraim; Sharma, Davendra M; Kitrey, Noam D; Djakovic, Nenad; Lumen, Nicolaas; Kuehhas, Franklin E; Summerton, Duncan J

    2017-05-29

    The management of high-grade (Grade IV-V) renal injuries remains controversial. There has been an increase in the use of (NOM) but limited data exists comparing outcomes with open surgical exploration. To conduct a systematic review to determine if NOM is the best first-line option for high-grade renal trauma in terms of safety and effectiveness. Medline, Embase, and Cochrane Library were searched for all relevant publications, without time or language limitations. The primary harm outcome was overall mortality and the primary benefit outcome was renal preservation rate. Secondary outcomes included length of hospital stay and complication rate. Single-arm studies were included as there were few comparative studies. Only studies with more than 50 patients were included. Data were narratively synthesised in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. Seven nonrandomised comparative and four single-arm studies were selected for data extraction. Seven hundred and eighty-seven patients were included from the comparative studies with 535 patients in the NOM group and 252 in the open surgical exploration group. A further 825 patients were included from single-arm studies. Results from comparative studies: overall mortality: NOM (0-3%), open surgical exploration (0-29%); renal preservation rate: NOM (84-100%), open surgical exploration (0-82%); complication rate: NOM (5-32%), open surgical exploration (10-76%). Overall mortality and renal preservation rate were significantly better in the NOM group whereas there was no statistical difference with regard to complication rate. Length of hospital stay was found be significantly reduced in the NOM group. Patients in the open surgical exploration group were more likely to have Grade V injuries, have a lower systolic blood pressure, and higher injury severity score on admission. No randomised controlled trials were identified and significant heterogeneity existed with

  10. [Criteria of ineffectiveness of treatment with first-line therapy: how to use MRI results in decision making?].

    Science.gov (United States)

    Khachanova, N V; Davydovskaya, M V

    2015-01-01

    The importance of MRI stuides in the control over treatment efficacy in multiple sclerosis and appropriate recommendations on drug substitution during treatment are discussed. We suggest low, middle or high risk in respect to the efficacy of current treatment. Accordingly, drug substitution can be related with the low level of fears for all three criteria or the moderate level for any two criteria or the high level for any one criterion. Since MRI criteria are important, this model appears to be the most rational because the physician can make a decision about treatment escalation if the patient has ≥3 new T2-lesions or ≥3 contrast-enhanced T1-lesions.

  11. Choice of antiretroviral drugs for continued treatment scale-up in a public health approach: what more do we need to know?

    Science.gov (United States)

    Vitoria, Marco; Hill, Andrew M; Ford, Nathan P; Doherty, Meg; Khoo, Saye H; Pozniak, Anton L

    2016-01-01

    There have been several important developments in antiretroviral treatment in the past two years. Randomized clinical trials have been conducted to evaluate a lower dose of efavirenz (400 mg once daily). Integrase inhibitors such as dolutegravir have been approved for first-line treatment. A new formulation of tenofovir (alafenamide) has been developed and has shown equivalent efficacy to tenofovir in randomized trials. Two-drug combination treatments have been evaluated in treatment-naïve and -experienced patients. The novel pharmacokinetic booster cobicistat has been compared to ritonavir in terms of pharmacokinetics, efficacy and safety. The objective of this commentary is to assess recent developments in antiretroviral drug treatment to determine whether new treatments should be included in new international guidelines. The use of first-line treatment with tenofovir and efavirenz at the standard 600 mg once-daily dose should remain the first-choice standard of care treatment. Evidence supporting a switch to efavirenz 400 mg once daily or integrase inhibitors is sufficient to consider these drugs as alternative first-line options, but more data are needed on their use in pregnant women and people with TB co-infection. The use of new formulations of tenofovir is currently too preliminary to justify immediate adoption and scale-up across HIV programmes in low- and middle-income countries. The evidence supporting use of two-drug combinations is not considered strong enough to justify changed recommendations from use of standard triple drug combinations. Cobicistat does not offer significant safety advantages over ritonavir as a pharmacokinetic booster. For continued scale-up of antiretroviral treatment in low- and middle-income countries, use of first-line triple combinations including efavirenz 600 mg once daily is supported by the largest evidence base. Additional studies are underway to evaluate new treatments in key populations, and these results may justify

  12. Long-term use of first-line highly active antiretroviral therapy is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients

    Directory of Open Access Journals (Sweden)

    Haohui Zhu

    2014-09-01

    Conclusion: The first-line highly active antiretroviral therapy currently used in China is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients with good highly active antiretroviral therapy compliance. Human immunodeficiency virus may play a role in the development of atherosclerosis.

  13. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study

    NARCIS (Netherlands)

    Homburg, R.R.; Hendriks, M.L.; König, T.E.; Anderson, R.A.; Balen, A.H.; Brincat, M.; Child, T.; Davies, M.; D'Hooghe, T.; Martinez, A; Rajkhowa, M.; Rueda-Saenz, R.; Hompes, P.G.A.; Lambalk, C.B.

    2012-01-01

    BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the

  14. The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

    Science.gov (United States)

    Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

    2013-01-01

    Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907

  15. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    Venook, Alan P.; Niedzwiecki, Donna; Lenz, Heinz-Josef; Innocenti, Federico; Fruth, Briant; Meyerhardt, Jeffrey A.; Schrag, Deborah; Greene, Claire; O’Neil, Bert H.; Atkins, James Norman; Berry, Scott; Polite, Blase N.; O’Reilly, Eileen M.; Goldberg, Richard M.; Hochster, Howard S.; Schilsky, Richard L.; Bertagnolli, Monica M.; El-Khoueiry, Anthony B.; Watson, Peter; Benson, Al B.; Mulkerin, Daniel L.; Mayer, Robert J.; Blanke, Charles

    2017-01-01

    IMPORTANCE Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. OBJECTIVE To determine if the addition of cetuximab vsbevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. INTERVENTIONS Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. MAIN OUTCOMES AND MEASURES The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. RESULTS Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0–110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77–1.01; P = .08). The

  16. Cost-effectiveness of First-line Chronic Lymphocytic Leukemia Treatments When Full-dose Fludarabine Is Unsuitable.

    Science.gov (United States)

    Soini, Erkki; Hautala, Anne; Poikonen, Eira; Becker, Ursula; Kyttälä, Mira; Martikainen, Janne

    2016-04-01

    The cost-effectiveness of first-line chronic lymphocytic leukemia treatments was assessed among patients unsuitable for full doses of fludarabine. The study's key outcome was the life-time incremental cost-effectiveness ratio (ICER) (euro/quality-adjusted life-year [QALY] gained) with an annual 3% discounting. A probabilistic Markov model with 3 health states (progression-free, progression, and death) was developed. Survival time was modeled based on age-matched clinical data by using appropriate survival distributions. Each health state was assigned an EuroQoL-5D-3L quality-of-life estimate and Finnish payer costs according to treatment received, and Binet stage of disease; severe adverse events and treatment inconvenience were also included. Six approaches considered the risk and value of key outcomes: cost-effectiveness efficiency frontiers; Bayesian treatment ranking (BTR) rated the lowest ICERs and best QALY gains; the cost-effectiveness acceptability frontier demonstrated optimal treatment; expected value of perfect information; and the cost-benefit assessment (CBA), a type of clinical value analysis, increased the clinical interpretation and appeal of modeled outcomes by including both relative and absolute (impact investment [benefit obtained with a fixed limited budget]) benefit assessments. The ICERs compared with chlorambucil varied from €29,334 with obinutuzumab + chlorambucil to €82,159 with ofatumumab + chlorambucil. Based on the BTR of ICERs versus chlorambucil, obinutuzumab + chlorambucil was the most cost-effective with 93% probability; rituximab + chlorambucil was the second most cost-effective (73%); and rituximab + bendamustine was the third most cost-effective (65%). The ICERs of obinutuzumab + chlorambucil were €20,038, €11,556, and €15,586 compared with rituximab + chlorambucil, rituximab + bendamustine, and ofatumumab + chlorambucil. Obinutuzumab + chlorambucil was the most cost-effective treatment, with 54% and 99% probability at

  17. Adding ofloxacin to standard triple-drug regimens increased the Helicobacter pylori eradication rate: Data from randomized clinical trial.

    Science.gov (United States)

    Sadeghi-Hadad-Zavareh, Mahmoud; Mohammadi, Seyyedsaeid; Hajiahmadi, Mahmoud; Javanian, Mostafa; Habibian, Masoomeh

    2017-01-01

    The rate of Helicobacter pylori (H.pylori) eradication in dyspeptic patients using bismuth- based triple therapy is low due to bacterial that are resistant to antibiotics. The results of recent studies regarding levofloxacin have been encouraging, but the high cost of treatment prevents its routine administration. We, therefore, performed the present double-blind clinical trial to compare the efficiency of quadruple-drug regimen containing ofloxacin, clarithromycin, amoxicillin, and omeprazole and the same standard triple-therapy regimen minus ofloxacin in H. pylori positive dyspepsia. The study patients were recruited among dyspeptic patients requiring gastroscopy. Patients with the history of H.pylori treatment, renal failure and pregnancy were excluded. Diagnosis of H.pylori infection was confirmed by rapid urease test and response to treatment was confirmed via negative urease breath test (UBT) 20 days after completion of treatment. Patients were allocated intermittently to standard triple therapy containing amoxicillin, clarithromycin, omeprazole alone or plus ofloxacin for ten days. Response to treatment was compared between the two groups. A total of 140 patients entered the study (70 patients in each group). At endpoint 30 (42.9%) patients of group 1 and 39 (55.7%) patients of group 2 became asymptomatic. Furthermore, 55 (78.6%) patients of group 1 and 66 (94.3%) patients of group 2 revealed negative urea breath test (P= 0.01). This study indicates adding ofloxacin to standard triple-therapy for H.pylorri infection significantly increases the rate of eradication. These findings highlight ofloxacin as empiric treatment of H. pylori infection.

  18. A study on Prevalence of Drug Resistance in Drug Default ...

    African Journals Online (AJOL)

    All culture positive sputa had drug sensitivity tested to the first line anti-TB drugs used in Sudan namely Streptomycin, Isoniazid, Rifampicin and Ethambutol. Results: Out of the 111 patients, 29.7% (n=33) were AFB sputum smear positive and 40.5% (n=45) were sputum culture positive for mycobacterium. Sensitivity testing ...

  19. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial

    NARCIS (Netherlands)

    Bois, A. du; Kristensen, G.; Ray-Coquard, I.; Reuss, A.; Pignata, S.; Colombo, N.; Denison, U.; Vergote, I.; Campo, J.M. Del; Ottevanger, P.B.; Heubner, M.; Minarik, T.; Sevin, E.; Gregorio, N. de; Bidzinski, M.; Pfisterer, J.; Malander, S.; Hilpert, F.; Mirza, M.R.; Scambia, G.; Meier, W.; Nicoletto, M.O.; Bjorge, L.; Lortholary, A.; Sailer, M.O.; Merger, M.; Harter, P.

    2016-01-01

    BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the

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

    Energy Technology Data Exchange (ETDEWEB)

    Palard-Novello, X. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Querellou, S.; Abgral, R.; Salauen, P.Y. [Brest University Hospital, Department of Nuclear Medicine, Brest Cedex (France); Brest University, EA3878, GETBO, IFR148, Brest (France); Gouillou, M. [Institut National de la Sante et de la Recherche Medicale (INSERM), Clinical Investigation Centre (CIC) 1412, Brest (France); Saraux, A.; Devauchelle-Pensec, V. [Brest University Hospital, Department of Rheumatology, Brest (France); Brest University, EA 2216, ESPRI 29, Brest (France); Marhadour, T. [Brest University Hospital, Department of Rheumatology, Brest (France); Garrigues, F. [Brest University Hospital, Department of Radiology, Brest (France)

    2016-04-15

    To evaluate the use of {sup 18}F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∇SUVmax and the other parameters including ∇PMR-AS, ∇CRP and ∇ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity. (orig.)

  1. A comparison of two methods for measuring anti-hypertensive drug use: concordance of use with South African standard treatment guidelines.

    Science.gov (United States)

    Pillay, Thamizhanban; Smith, Anthony J; Hill, Suzanne R

    2009-06-01

    To assess prescriber adherence to standard anti-hypertensive treatment guidelines in South Africa, determine if supply data are useful indicators of drug use, and assess the cost implications of not complying with the guidelines. We undertook two studies: an analysis of records of the anti-hypertensive drugs supplied to all 54 public-sector hospitals with a hypertension clinic in KwaZulu-Natal, and a direct-observation survey of anti-hypertensive drug prescriptions presented to pharmacies in a subset of 16 of the 54 hospitals. We calculated the relative use of each anti-hypertensive drug group as a proportion of all anti-hypertensive drugs supplied or prescribed. We ranked drug groups in order of use for comparison with recommended South African standard treatment guidelines, and we compared the proportions derived from supply data with those derived from the prescription survey. Supply data showed that, in line with treatment guidelines, diuretics and angiotensin-converting enzyme inhibitors were the most frequently supplied medicines (42% and 27%, respectively). However, methyldopa - not included in the treatment guidelines - represented 10% of all anti-hypertensives supplied, but the proportion varied widely between hospitals (0-37%). Reserpine, second choice in the treatment guidelines, was used in high amounts by only two hospitals. Calcium channel blockers and beta blockers represented a small proportion of the anti-hypertensive drugs supplied: 6% each. Results from the prescription survey were in concordance with supply data for the most frequently prescribed drugs but gave slightly different estimates of the use of others. Supply data, the most available source of information about drug use in developing countries, are (with some provisos) a reliable data source for the evaluation of adherence to treatment guidelines. Our results showed substantial non-adherence to standard treatment guidelines.

  2. [Accreditation standards concerning patients' rights: a review of the current state of affairs related to drug-addiction treatment centers in Colombia].

    Science.gov (United States)

    Zapata-Vanegas, Mario A

    2014-01-01

    Characterizing and contrasting the current state of affairs concerning patients' rights-associated accreditation standards in a sample of drug-addiction treatment centers in Colombia. This was mixed methodology research (i.e. descriptive and hermeneutic); a pilot sample of 21 drug-addiction treatment centers in Colombia was used for determining the current state of patients' rights accreditation standards. The possible relationship or independence between categorical variables was evaluated by using Fisher's exact test (0.05 significance level). A contrasting documentary review was made at the same time. Drug-addiction treatment centers provided more information for families (95 %) than patients (90 %) or minors (81 %). Possible barriers to gaining access for treatment were being HIV positive (29 %), being part of the LGTB population (14 %) and being female (10 %); religion and ethnicity were not seen as grounds for discrimination or treatment barriers. The patients' rights standards group coincided with Colombia's accreditation system and Joint Commission standards; however, the latter accreditation entity has made significant progress regarding a specific manual for drug-addiction treatment centers. The centers assessed in Colombia had made advances regarding accrediting patients' rights, but such standards require revision for being adapted to international developments and specific matters involved in treating addicts and the specific conditions for institutions dealing with such treatment.

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

    Directory of Open Access Journals (Sweden)

    Baran Y

    2012-11-01

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

  4. The Most Prevalent Organism in Diabetic Foot Ulcers and Its Drug Sensitivity and Resistance to Different Standard Antibiotics.

    Science.gov (United States)

    Nageen, Ayesha

    2016-04-01

    To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics. Adescriptive and cross-sectional study. Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012. Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted. Staphylococcus aureuswas the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients. Staphylococcus aureuswas the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole.

  5. Emerging concepts on drug resistance in bladder cancer: Implications for future strategies.

    Science.gov (United States)

    Massari, Francesco; Santoni, Matteo; Ciccarese, Chiara; Brunelli, Matteo; Conti, Alessandro; Santini, Daniele; Montironi, Rodolfo; Cascinu, Stefano; Tortora, Giampaolo

    2015-10-01

    The combination chemotherapies with methotrexate plus vinblastine, doxorubicin and cisplatin (MVAC or CMV regimens) or gemcitabine plus cisplatin represent the standard as first-line therapy for patients with metastatic urothelial cancer. In Europe, vinflunine is an option for second-line therapy for patients progressed during first-line or perioperative platinum-containing regimen. Alternative regimens containing taxanes and/or gemcitabine may be valuated case by case. Furthermore, carboplatin should be considered in patients unfit for cisplatin both in the first and second-line setting. Based on these findings, a better comprehension of the mechanisms underlying the development of drug resistance in patients with bladder cancer will represent a major step forward in optimizing patients' outcome. This article reviews the current knowledge of the mechanisms and emerging strategies to overcome resistance in patients with advanced urothelial cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

    NARCIS (Netherlands)

    Gregson, John; Tang, Michele; Ndembi, Nicaise; Hamers, Raph L.; Rhee, Soo-Yon; Marconi, Vincent C.; Diero, Lameck; Brooks, Katherine; Theys, Kristof; de Wit, Tobias F. Rinke; Arruda, Monica; Garcia, Frederico; Monge, Susana; Gunthard, Huldrych F.; Hoffmann, Christopher J.; Kanki, Phyllis J.; Kumarasamy, Nagalingeshwaran; Kerschberger, Bernard; Mor, Orna; Charpentier, Charlotte; Todesco, Eva; Rokx, Casper; Gras, Luuk; Halvas, Elias K.; Sunpath, Henry; Di Carlo, Domenico; Antinori, Antonio; Andreoni, Massimo; Latini, Alessandra; Mussini, Cristina; Aghokeng, Avelin; Sonnerborg, Anders; Neogi, Ujjwal; Fessel, William J.; Agolory, Simon; Yang, Chunfu; Blanco, Jose L.; Juma, James M.; Smit, Erasmus; Schmidt, Daniel; Watera, Christine; Asio, Juliet; Kirungi, Wilford; Tostevin, Anna; El-Hay, Tal; Clumeck, Nathan; Goedhals, Dominique; van Vuuren, Cloete; Bester, Philip Armand; Sabin, Caroline; Mukui, Irene; Santoro, Maria M.; Perno, Carlo F.; Hunt, Gillian; Morris, Lynn; Camacho, Ricardo; de Oliveira, Tulio; Pillay, Deenan; Schulter, Eugene; Murakami-Ogasawara, Akio; Reyes-Teran, Gustavo; Romero, Karla; Avila-Rios, Santiago; Sirivichayakul, Sunee; Ruxrungtham, Kiat; Mekprasan, Suwanna; Dunn, David; Kaleebu, Pontiano; Raizes, Elliot; Kantor, Rami; Shafer, Robert W.; Gupta, Ravindra K.

    2016-01-01

    Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for

  7. Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran

    Directory of Open Access Journals (Sweden)

    Djadid Navid

    2007-11-01

    Full Text Available Abstract Background This work was carried out to assess the patterns and prevalence of resistance to chloroquine (CQ and sulphadoxine-pyrimethamine (SP in Iran. Methods The prevalence of pfcrt K76T, pfmdr1 N86Y, pfdhfr N51I, C59R, S108N/T and I164L and codons S436F/A, A437G, K540E, A581E, and A613S/T in pfdhps genes were genotyped by PCR/RFLP methods in 206 Plasmodium falciparum isolates from Chabahar and Sarbaz districts in Sistan and Baluchistan province, Iran, during 2003–2005. Results All P. falciparum isolates carried the 108N, while 98.5% parasite isolates carried the 59R mutation. 98.5% of patients carried both 108N and 59R. The prevalence of pfdhps 437G mutation was 17% (Chabahar and 33% (Sarbaz isolates. 20.4% of samples presented the pfdhfr 108N, 59R with pfdhps 437G mutations. The frequency of allele pfcrt 76T was 98%, while 41.4% (Chabahar and 27.7% (Sarbaz isolates carried pfmdr1 86Y allele. Eight distinct haplotypes were identified in all 206 samples, while the most prevalent haplotype was T76/N86/N51R59N108/A437 among both study areas. Conclusion Finding the fixed level of CQ resistance polymorphisms (pfcrt 76T suggests that CQ must be withdrawn from the current treatment strategy in Iran, while SP may remain the treatment of choice for uncomplicated malaria.

  8. Protocol for Combined Analysis of FOXFIRE, SIRFLOX, and FOXFIRE-Global Randomized Phase III Trials of Chemotherapy +/- Selective Internal Radiation Therapy as First-Line Treatment for Patients With Metastatic Colorectal Cancer.

    Science.gov (United States)

    Virdee, Pradeep S; Moschandreas, Joanna; Gebski, Val; Love, Sharon B; Francis, E Anne; Wasan, Harpreet S; van Hazel, Guy; Gibbs, Peter; Sharma, Ricky A

    2017-03-28

    facilitate comparisons of low frequency adverse events and allow for more robust safety analyses. The potential treatment benefit in those patients who present with disease confined to the liver will be investigated using 1-stage IPD meta-analysis. Efficacy will be analyzed on an intention-to-treat basis. This analysis will assess the impact of SIRT combined with chemotherapy on overall survival in the first-line treatment of metastatic CRC. If positive, the results will change the standard of care for this disease. FOXFIRE ISRCTN Registry ISRCTN83867919; http://www.isrctn.com/ISRCTN83867919 (Archived by WebCite at http://www.webcitation.org/6oN7axrvA). SIRFLOX ClinicalTrials.gov NCT00724503; https://clinicaltrials.gov/ ct2/show/NCT00724503 (Archived by WebCite at http://www.webcitation.org/6oN7lEGbD). FOXFIRE-Global ClinicalTrials.gov NCT01721954; https://clinicaltrials.gov/ct2/show/NCT01721954 (Archived by WebCite at http://www.webcitation.org/ 6oN7vvQvG).

  9. Prognostic significance of a systemic inflammatory response in patients receiving first-line palliative chemotherapy for recurred or metastatic gastric cancer

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    Hwang Jun-Eul

    2011-11-01

    Full Text Available Abstract Background There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor prognosis in patients with advanced cancers. We evaluated the relationships between clinical status, laboratory factors and progression free survival (PFS, and overall survival (OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Methods We reviewed 402 patients with advanced gastric adenocarcinoma who received first-line palliative chemotherapy from June 2004 and December 2009. Various chemotherapy regimens were used. Eastern Cooperative Oncology Group performance status (ECOG PS, C-reactive protein (CRP, albumin, Glasgow prognostic score (GPS, and clinical factors were recorded immediately prior to first-line chemotherapy. Patients with both an elevated CRP (>1.0 mg/dL and hypoalbuminemia ( Results According to multivariate analysis, the factors independently associated with PFS were ECOG PS (HR 1.37, 95% CI 1.02-1.84, P = 0.035, bone metastasis (HR 1.74, 95% CI 1.14-2.65, P = 0.009, and CRP elevation (HR 1.64, 95% CI 1.28-2.09, P = 0.001. The factors independently associated with OS were ECOG PS (HR 1.33, 95% CI 1.01-1.76, P = 0.037, bone metastasis (HR 1.61, 95% CI 1.08-2.39, P = 0.017, and GPS ≥ 1 (HR 1.76, 95% CI 1.41-2.19, P = 0.001. Conclusions The results of this study showed that the presence of a systemic inflammatory response as evidenced by the CRP, GPS was significantly associated with shorter PFS and OS in patients with recurrent or metastatic gastric cancer receiving first-line palliative chemotherapy. Bone metastasis and GPS were very useful indicator for survival in patients with recurrent or metastatic gastric cancer receiving palliative chemotherapy.

  10. First-line managers' views of the long-term effects of clinical supervision: how does clinical supervision support and develop leadership in health care?

    Science.gov (United States)

    Hyrkäs, Kristiina; Appelqvist-Schmidlechner, Kaija; Kivimäki, Kirsti

    2005-05-01

    There have recently been several organizational changes that have challenged nursing managers in the Finnish health care system. First-line managers need support in their work because of organizational changes and scarce economic resources. One of these supportive measures is clinical supervision. A group of first-line managers in a Finnish University hospital participated in a 2-year clinical supervision intervention in 1999-2000. The managers' perceptions of the clinical supervision were followed up twice during the intervention and 1 year after (2001). The aim of this study is to describe how the first-line managers saw the future effects of the clinical supervision intervention 1 year after its termination. At the beginning of the intervention, the number of participating nursing managers was 32. The number of respondents in this study 1 year (2001) after the clinical supervision was 11. Data was collected using empathy-based stories, which involved writing short essays. The respondents received orientation and a script to assist them in the writing of essays. The stories were analysed qualitatively by categorizing the responses by themes. The managers deemed that clinical supervision had, in the 3-year time frame, positive long-term effects on their leadership and communication skills, the desire for self-development, self-knowledge and coping. Managers believed that in the long run, clinical supervision would provide them with a broader perspective on work and would enhance the use of clinical supervision as a supportive measure among co-workers. First-line managers expect clinical supervision to have long-term positive effects on their work and coping. Empathy-based stories, as a method, were found suited to studies, which aim to obtaining future-oriented knowledge.

  11. Estimated Life-Years Saved in Women with HER2-Positive Metastatic Breast Cancer Receiving First-Line Trastuzumab and Pertuzumab in the United States.

    Science.gov (United States)

    Danese, Mark D; Masaquel, Anthony; Santos, Eduardo; Brammer, Melissa; Lee, Abraham; Lalla, Deepa

    2015-09-01

    HER2 positive (HER2+) metastatic breast cancer (MBC) is associated with high mortality. Trastuzumab was approved for use in 1998, but the life-years saved from first-line use are unknown, as are the potential US population benefits from adding pertuzumab. The first aim was to estimate the number of life-years saved by using first-line trastuzumab between 1999 and 2013 in HER2+ women with MBC. In addition, based on these estimates, the second aim was to project the life-years that could be saved by adding pertuzumab to trastuzumab in first-line therapy. We constructed a simulation model accounting for incidence, testing rates, therapy utilization, and overall survival. The model was run for 1999 to 2013 (15 years) to estimate the life-years saved from using trastuzumab plus chemotherapy instead of chemotherapy alone. The model was also run from 2013 to 2027 (15 years) to project the life-years that might be saved by adding pertuzumab. Uncertainty was incorporated using Monte-Carlo methods. The estimated number of women with HER2+ MBC varied over time, with the peak of 9700 in 2005 and the low of 7700 in 2018. The cumulative incremental life-years saved because of first-line trastuzumab use from 1999 to 2013 was estimated to be 156,413 (95% simulation interval 114,840-195,201). The projection for pertuzumab from 2013 to 2027 was 137,959 (95% simulation interval 56,011-225,069). Exploratory analyses of value showed that pertuzumab, trastuzumab, and chemotherapy is associated with a $1.10 billion gain compared with chemotherapy alone, and adding pertuzumab is associated with a $0.06 billion gain compared with trastuzumab with chemotherapy. This simulation model suggests that substantial progress has been made in treating HER2+ women over the past 15 years, and the future may witness similar gains with the introduction of pertuzumab. Copyright © 2015. Published by Elsevier Inc.

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

    Science.gov (United States)

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

    2017-08-01

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

  13. Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial.

    Science.gov (United States)

    Stingl, Julia Carolin; Kaumanns, Katharina Luise; Claus, Katrin; Lehmann, Marie-Louise; Kastenmüller, Kathrin; Bleckwenn, Markus; Hartmann, Gunther; Steffens, Michael; Wirtz, Dorothee; Leuchs, Ann-Kristin; Benda, Norbert; Meier, Florian; Schöffski, Oliver; Holdenrieder, Stefan; Coch, Christoph; Weckbecker, Klaus

    2016-04-26

    Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects. The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk "index drugs" oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients' adherence to medication regimen as well as health related quality of life

  14. Application of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor as the First-line Therapy in Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chunsun LI

    2010-01-01

    Full Text Available Background and objective Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI has been widely used as the second- and third-line therapy in patients with advanced non-small cell lung cancer (NSCLC. However, its effect in the first-line treatment is unclear. The aim of this study was to evaluate the efficacy and safety of EGFRTKI as first-line therapy. Methods The clinical characteristics, responses rate, disease control rate and overall survival were retrospectively analyzed in 77 chemonaive patients with advanced NSCLC. All of the patients received oral gefitinib (250 mg/d or erlotinib (150 mg/d until disease progression or unacceptable toxicity occurrence. Results The overall response rate was 33.8% and the disease control rate was 68.8%. The median progression-free survival and the median survival time were 6.0 months and 8.9 months, respectively. One-year survival rate was 61.4%. Responses correlated significantly with histology, PS score, smoking history, skin rash, EGFR mutations and serum CEA. Histology and skin rash were the independent predictors of survival. Common toxicities were skin rash and mild diarrhea. EGFR-TKI could improve the clinical symptoms and the quality of life. Conclusion EGFR-TKI is effective and well tolerated as first-line therapy in patients with advanced NSCLC.

  15. [Clinical Experience of S-1 and Oxaliplatin(SOX)as the First-Line Chemotherapy for Metastatic/Recurrent Gastric Cancer].

    Science.gov (United States)

    Toyokawa, Takahiro; Tamura, Tatsuro; Shibutani, Masatsune; Ohira, Goh; Yamazoe, Sadaaki; Kimura, Kenjiro; Nagahara, Hisashi; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Hirakawa, Kosei; Ohira, Masaichi

    2017-05-01

    We retrospectively investigated the efficacy and safety of S-1 and oxaliplatin(SOX)as the first-line chemotherapy in patients with metastatic/recurrent gastric cancer. A total of 27 patients who received SOX as the first-line chemotherapy in our hospital were considered for the study. The SOX chemotherapy schedule consisted of 1 course every 3 weeks. S-1 was administered orally, at 80-120mg-body, every day for 14 days. Oxaliplatin was infused at 100mg/m2 on day 1 of each course. The median number of treatment courses was 7. The response rate and disease control rate were 47.6% and 76.2%, respectively. The observed adverse events of Grade 3 or more included neutropenia(33.3%); peripheral neuropathy and anorexia(11.1%); thrombocytopenia(7.4%); and anemia, diarrhea, fatigue, and hypercalcemia(3.7%). The median overall survival was not achieved, and the 1-year survival rate was 63.2%. Therefore, SOX is an effective and feasible first-line chemotherapy that is easily available for ambulatory treatment of patients with metastatic/recurrent gastric cancer.

  16. Psychometric testing of the Leadership and Management Inventory: a tool to measure the skills and abilities of first-line nurse managers.

    Science.gov (United States)

    Skytt, Bernice; Carlsson, Marianne; Ljunggren, Birgitta; Engström, Maria

    2008-10-01

    To estimate the validity and reliability of the Leadership and Management Inventory, a tool to measure the skills and abilities of first-line nurse managers. The decision to develop an inventory reflects the need for an instrument that can measure the various skills and abilities first-line nurse managers should possess. Factor analysis was conducted and internal consistency initially estimated on data from 149 registered nurses; a second sample of 197 health care personnel was used to test these results. Principal component analysis of the first sample resulted in a preferred three-factor solution that explained 65.8% of the variance; Cronbach's alpha coefficient varied between 0.90 and 0.95. Analysis of the second sample also resulted in a three-factor solution that explained 64.2% of the variance; Cronbach's alpha coefficient varied from 0.88 to 0.96. For both samples, the factors were labelled 'interpersonal skills and group management', 'achievement orientation' and 'overall organizational view and political savvy'. Results indicate that estimates of validity and reliability for the Leadership and Management Inventory can be considered acceptable. The Leadership and Management Inventory can be used when first-line nurse managers' leadership and management skills and abilities are to be measured.

  17. Preliminary study of the effects of an educational workshop on therapeutic use of music and aesthetic experience with music in first-line nurses.

    Science.gov (United States)

    Lai, Hui-Ling

    2011-11-01

    The purpose of this study was to assess the effects of an educational workshop on knowledge of and attitude toward therapeutic use of music and aesthetic experiences with music among first-line nurses. A one-group pre-test/post-test design was used. Forty-six first-line nurses, aged 21-56 years, were recruited from seven different hospitals. Questionnaires were used to assess the nurses' knowledge of and attitude toward therapeutic use of music and aesthetic experience with music before and after the workshop, and 3 months after the workshop. The workshop comprised three sessions; the nurses participated in 8h of instruction the first week and 4h, the second week covering analytical music appreciation, music staves comprehension, theory and practice of music therapy, and evidence-based music intervention. Educational workshop significantly improved knowledge of and attitudes toward therapeutic use of music and music aesthetic experiences (peffect of the workshop was found at follow up 3-month after workshop. The mean change in scores for music aesthetic experiences between nurse with and without music backgrounds differed significantly (p=0.01). The workshop enhanced the knowledge of and attitude toward therapeutic use of music and aesthetic experiences with music among first-line nurses. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Efficacy and safety of a combination of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer: a network meta-analysis.

    Science.gov (United States)

    Leung, Henry W C; Leung, John-Hang; Chan, Agnes L F

    2018-01-01

    Using network meta-analysis, we assessed the efficacy and safety of a combination regimen of HER2-targeted agents as first-line treatment for metastatic HER2-positive breast cancer. We searched the Medline, Embase, and Cochrane Library electronic databases (through December 2016) for phase II/III randomized controlled trials that compared regimens of one or two HER2-targeted agents combined with trastuzumab or chemotherapy. A network meta-analysis including direct and indirect analyses was conducted in WinBUGS using fixed and random effects. Study quality was assessed following the Grading of Recommendations, Assessment, Development and Evaluations method. The primary outcome was overall survival. The network meta-analysis incorporated nine HER2-targeted regimens with 9 direct comparisons and 28 indirect comparisons for the main outcomes (8 studies; n = 3976). Combining direct and indirect effects showed significant increased efficacy of trastuzumab and docetaxel plus pertuzumab (TDP) over other regimens as first-line treatment. With indirect comparison of overall safety, TDP, TDM-1, and TDM-1 plus pertuzumab demonstrated a lower risk of grade 3-4 adverse events compared to other regimens. TDPs are a preferred first-line treatment for HER2-positive metastatic breast cancer compared with other target agent regimens.

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

    Directory of Open Access Journals (Sweden)

    Macedo Ligia

    2012-03-01

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

  20. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.

    Science.gov (United States)

    Marty, Michel; Cognetti, Francesco; Maraninchi, Dominique; Snyder, Ray; Mauriac, Louis; Tubiana-Hulin, Michèle; Chan, Stephen; Grimes, David; Antón, Antonio; Lluch, Ana; Kennedy, John; O'Byrne, Kenneth; Conte, PierFranco; Green, Michael; Ward, Carol; Mayne, Karen; Extra, Jean-Marc

    2005-07-01

    This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Patients were randomly assigned to six cycles of docetaxel 100 mg/m2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity.

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

    Directory of Open Access Journals (Sweden)

    Stephen Wright

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

  2. Standard additions-dilution method for absolute quantification in voltammetry of microparticles. Application for determining psychoactive 1,4-benzodiazepine and antidepressants drugs as adulterants in phytotherapeutic formulations.

    Science.gov (United States)

    Doménech-Carbó, Antonio; Martini, Mariele; de Carvalho, Leandro Machado; Viana, Carine; Doménech-Carbó, María Teresa; Silva, Miguel

    2013-06-01

    A standard additions-dilution solid-state electrochemical method for the determination of psychoactive 1,4-benzodiazepine and antidepressants drugs used as adulterants in commercial slimming herbal formulations is described and compared with conventional standard addition method. The proposed method, based on the voltammetry of microparticles approach, permits quantify, via standard additions methodology, 1,4-benzodiazepine and antidepressants drugs in phytotherapeutic formulations with no need of sample dissolution using dilution with a reference electroactive compound. The method was used to measure 1,4-benzobenzodiazepines (clonazepam, flurazepam, alprazolam, midazolam, bromazepam, chlordiazepoxide, lorazepam and diazepam) and antidepressants (bupropion, sertraline, paroxetine and fluoxetine) in slimming formulations that have been commercialized in Brazil. Copyright © 2013 Elsevier B.V. All rights reserved.