Sample records for factors influencing cytarabine

  1. Cytarabine

    MedlinePlus

    Cytarabine is used alone or with other chemotherapy drugs to treat certain types of leukemia (cancer of ... lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). Cytarabine is also used alone or with other chemotherapy ...

  2. Pharmacodynamics of cytarabine induced leucopenia: a retrospective cohort study

    PubMed Central

    Shepshelovich, Daniel; Edel, Yonatan; Goldvaser, Hadar; Dujovny, Tal; Wolach, Ofir; Raanani, Pia

    2015-01-01

    AIMS Cytarabine is a pyrimidine analogue used to treat a variety of haematological malignancies. There are few data regarding the pharmacodynamics of cytarabine. The only publications regarding this issue cite a biphasic pattern of decline in white blood cell (WBC) counts following low and intermediate doses, in patients with various malignancies, most of them non-haematological. Our purpose was to establish the pharmacodynamics of cytarabine induced leucopenia in acute myeloid leukaemia (AML) patients treated with contemporary cytarabine containing protocols. METHODS We conducted a retrospective cohort study, including 56 patients with AML in complete remission who had received 89 cycles of intermediate or high dose cytarabine. Daily counts for WBCs and neutrophils (ANC) were collected during the first 15 days after the initiation of cytarabine administration and pharmacodynamics were analyzed. Further analysis was carried out to correlate between WBC and ANC pharmacodynamics and different cytarabine protocols [high dose cytarabine (HiDAC) vs. intermediate dose cytarabine (IDAC)]. RESULTS Analysis of blood counts demonstrated a monophasic decline of WBCs and ANCs, unlike a previous depiction of a biphasic pattern. HiDAC was associated with a significantly sharper decline of WBCs than IDAC. CONCLUSIONS Our data support a monophasic decline pattern of WBCs and ANCs following contemporary cytarabine protocols. The decline rate is steeper for patients receiving HiDAC than for those receiving IDAC. These results might help form evidence based guidelines regarding patient monitoring intensity, timing of prophylactic antibacterial and antifungal treatment as well as growth factors' support following cytarabine based consolidation for AML. PMID:25303309

  3. Pharmacodynamics of cytarabine induced leucopenia: a retrospective cohort study.

    PubMed

    Shepshelovich, Daniel; Edel, Yonatan; Goldvaser, Hadar; Dujovny, Tal; Wolach, Ofir; Raanani, Pia

    2015-04-01

    Cytarabine is a pyrimidine analogue used to treat a variety of haematological malignancies. There are few data regarding the pharmacodynamics of cytarabine. The only publications regarding this issue cite a biphasic pattern of decline in white blood cell (WBC) counts following low and intermediate doses, in patients with various malignancies, most of them non-haematological. Our purpose was to establish the pharmacodynamics of cytarabine induced leucopenia in acute myeloid leukaemia (AML) patients treated with contemporary cytarabine containing protocols. We conducted a retrospective cohort study, including 56 patients with AML in complete remission who had received 89 cycles of intermediate or high dose cytarabine. Daily counts for WBCs and neutrophils (ANC) were collected during the first 15 days after the initiation of cytarabine administration and pharmacodynamics were analyzed. Further analysis was carried out to correlate between WBC and ANC pharmacodynamics and different cytarabine protocols [high dose cytarabine (HiDAC) vs. intermediate dose cytarabine (IDAC)]. Analysis of blood counts demonstrated a monophasic decline of WBCs and ANCs, unlike a previous depiction of a biphasic pattern. HiDAC was associated with a significantly sharper decline of WBCs than IDAC. Our data support a monophasic decline pattern of WBCs and ANCs following contemporary cytarabine protocols. The decline rate is steeper for patients receiving HiDAC than for those receiving IDAC. These results might help form evidence based guidelines regarding patient monitoring intensity, timing of prophylactic antibacterial and antifungal treatment as well as growth factors' support following cytarabine based consolidation for AML. © 2014 The British Pharmacological Society.

  4. Severe palmar-plantar erythrodysesthesia and aplasia in an adult undergoing re-induction treatment with high-dose cytarabine for acute myelogenous leukemia: a possible drug interaction between posaconazole and cytarabine.

    PubMed

    Alzghari, Saeed K; Seago, Susan E; Cable, Christian T; Herrington, Jon D

    2017-09-01

    High-dose cytarabine is recommended for re-induction chemotherapy in patients less than 60 years of age with acute myelogenous leukemia. This case describes a patient receiving high-dose cytarabine for re-induction and subsequently developed tingling and numbness in her hands and feet followed by severe pain, swelling, and erythema consistent with a diagnosis of palmar-plantar erythrodysesthesia. Furthermore, the patient's hemoglobin, platelets, and neutrophils did not recover after over 30 days post high-dose cytarabine. The patient was concurrently receiving posaconazole for fungal prophylaxis which was initiated after the induction therapy. We speculate that posaconazole may inhibit the cytarabine efflux through P-glycoprotein inhibition leading to the patient's palmar-plantar erythrodysesthesia and subsequent aplasia. Future pharmacokinetic studies need to be conducted to ascertain if posaconazole does influence the pharmacokinetics of cytarabine.

  5. Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel as an efficient cytarabine delivery system.

    PubMed

    Liu, Jing; Jiang, Yue; Cui, Yuting; Xu, Chuanshan; Ji, Xiaoqing; Luan, Yuxia

    2014-10-01

    Carrier with high drug loading content is one of the most important issues in drug delivery system. In the present work, an ion-pair amphiphilic molecule composed of anticancer drug cation and surfactant anion is used for straightforward fabricating vesicles for cancer therapy. Anticancer drug (cytarabine hydrochloride) and anionic surfactant (AOT) are selected for the fabrication of ion-pair amphiphilic molecule. One amphiphilic molecule contains one drug cation, thus the drug loading content is 50% (mol/mol) in theory. The in vitro drug release study shows that the release time of cytarabine is about 3 times of the pure cytarabine solution and the permeability of cytarabine has been improved about 160 times tested by parallel artificial membrane permeability assay model. However, the hemolytic toxicity is largely decreased in the studied concentration range. The in vitro cytotoxicity results show that cytarabine-AOT amphiphiles have a much lower IC50 (drug concentration resulting in 50% cell death) value and a higher cell inhibition rate comparing with their respective components, indicating its effective therapy for leukemic cells. To obtain a longer and a convenient drug release system, the prepared vesicles are further incorporated into the thermosensitive PLGA-PEG-PLGA hydrogel to prepare a subcutaneous administration. The in vivo drug release results indicate that cytarabine-AOT vesicle-loaded hydrogel is a good injectable delivery system for controlled release of cytarabine for cancer therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Cytarabine Lipid Complex Injection

    MedlinePlus

    Cytarabine lipid complex comes as a liquid to be injected intrathecally (into the fluid-filled space of the spinal canal) over 1 to 5 minutes by a doctor or nurse in a medical facility. At first, cytarabine lipid ...

  7. Comparison of consolidation strategies in acute myeloid leukemia: high-dose cytarabine alone versus intermediate-dose cytarabine combined with anthracyclines.

    PubMed

    Kim, Dae Sik; Kang, Ka-Won; Lee, Se Ryeon; Park, Yong; Sung, Hwa Jung; Kim, Seok Jin; Choi, Chul Won; Kim, Byung Soo

    2015-09-01

    We compared the efficacy of high-dose cytarabine alone to that of intermediate-dose cytarabine combined with anthracyclines as consolidation therapy. Patients enrolled in the Korea University acute myeloid leukemia (AML) registry received remission induction chemotherapy with the same standard induction regimen (idarubicin and cytarabine 3 + 7). Postremission therapy was performed for three or four cycles according to one of the following regimens: high-dose cytarabine (3 g/m(2)) or combination of intermediate-dose cytarabine (1 g/m(2)) with anthracyclines (idarubicin or mitoxantrone). Among the 443 AML patients enrolled in the registry, 145 patients received consolidation chemotherapy. The median overall survival (OS) and relapse-free survival (RFS) in the high-dose cytarabine group were significantly longer than those in the anthracycline combination group (OS, not reached vs. 16.6 months, p = 0.045; RFS, 38.6 months vs. 11.0 months, p = 0.011). The median duration of neutropenia was longer in the anthracycline combination group than in the high-dose cytarabine group (8 vs. 10 days, p = 0.001). This study suggests that high-dose cytarabine consolidation may produce superior outcomes than combination treatment with intermediate-dose cytarabine and anthracyclines and that the addition of anthracyclines during AML consolidation has limited value as compared to cytarabine intensification.

  8. Clinical significance of in vivo cytarabine-induced gene expression signature in AML.

    PubMed

    Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R; Cogle, Christopher R; Bhise, Neha; Raimondi, Susana C; Downing, James R; Baker, Sharyn D; Ribeiro, Raul C; Rubnitz, Jeffrey E

    2016-01-01

    Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

  9. Influence of cytarabine metabolic pathway polymorphisms in acute myeloid leukemia induction treatment.

    PubMed

    Megías-Vericat, Juan Eduardo; Montesinos, Pau; Herrero, María José; Moscardó, Federico; Bosó, Virginia; Martínez-Cuadrón, David; Rojas, Luis; Rodríguez-Veiga, Rebeca; Boluda, Blanca; Sendra, Luis; Cervera, José; Poveda, José Luis; Sanz, Miguel Ángel; Aliño, Salvador F

    2017-12-01

    Cytarabine is considered the most effective chemotherapeutic option in acute myeloid leukemia (AML). The impact of 10 polymorphisms in cytarabine metabolic pathway genes were evaluated in 225 adult de novo AML patients. Variant alleles of DCK rs2306744 and CDA rs602950 showed higher complete remission (p = .024, p = .045), with lower survival rates for variant alleles of CDA rs2072671 (p = .015, p = .045, p = .032), rs3215400 (p = .033) and wild-type genotype of rs602950 (p = .039, .014). Induction death (p = .033) and lower survival rates (p = .021, p = .047) were correlated to RRM1 rs9937 variant allele. In addition, variant alleles of CDA rs532545 and rs602950 were related to skin toxicity (p = .031, p = .049) and mucositis to DCK rs2306744 minor allele (p = .046). Other toxicities associated to variant alleles were hepatotoxicity to NT5C2 rs11598702 (p = .032), lung toxicity (p = .031) and thrombocytopenia to DCK rs4694362 (p = .046). This study supports the interest of cytarabine pathway polymorphisms regarding efficacy and toxicity of AML therapy in a coherent integrated manner.

  10. Clinical significance of In vivo Cytarabine Induced Gene Expression Signature in AML

    PubMed Central

    Lamba, Jatinder K.; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R.; Cogle, Christopher R.; Bhise, Neha; Raimondi, Susana C.; Downing, James R.; Baker, Sharyn D.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.

    2016-01-01

    Despite initial remission, approximately 60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML, however extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy can trigger adaptive response by influencing leukemic cell transcriptome and hence development of resistance or refractory disease. It is however challenging to perform such a study due to lack of availability of specimens post-drug treatment. In this study our primary objective was to identify in vivo cytarabine induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. Our results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response. PMID:26366682

  11. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

    PubMed

    Ravandi, Farhad; Ritchie, Ellen K; Sayar, Hamid; Lancet, Jeffrey E; Craig, Michael D; Vey, Norbert; Strickland, Stephen A; Schiller, Gary J; Jabbour, Elias; Erba, Harry P; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M; Cortes, Jorge; Roboz, Gail J; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R; Fox, Judith A; Ward, Renee; Smith, Jennifer A; Acton, Gary; Mehta, Cyrus; Stuart, Robert K; Kantarjian, Hagop M

    2015-09-01

    patients, p<0·0001). Early mortality was similar between treatment groups (30-day: 28 [8%] of 355 patients in the vosaroxin plus cytarabine group vs 23 [7%] of 350 in the placebo plus cytarabine group; 60-day: 70 [20%] vs 68 [19%]). Treatment-related deaths occurred at any time in 20 (6%) of 355 patients given vosaroxin plus cytarabine and in eight (2%) of 350 patients given placebo plus cytarabine. Treatment-related serious adverse events occurred in 116 (33%) and 58 (17%) patients in each group, respectively. Grade 3 or worse adverse events that were more frequent in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group included febrile neutropenia (167 [47%] vs 117 [33%]), neutropenia (66 [19%] vs 49 [14%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), bacteraemia (43 [12%] vs 16 [5%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Although there was no significant difference in the primary endpoint between groups, the prespecified secondary analysis stratified by randomisation factors suggests that the addition of vosaroxin to cytarabine might be of clinical benefit to some patients with relapsed or refractory acute myeloid leukaemia. Sunesis Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Daunorubicin and Cytarabine Lipid Complex Injection

    MedlinePlus

    Daunorubicin and cytarabine lipid complex is used to treat certain types of acute myeloid leukemia (AML; a type of cancer of ... is in a class of medications called anthracyclines. Cytarabine is in a class of medications called antimetabolites. ...

  13. Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients.

    PubMed

    Röllig, C; Kramer, M; Gabrecht, M; Hänel, M; Herbst, R; Kaiser, U; Schmitz, N; Kullmer, J; Fetscher, S; Link, H; Mantovani-Löffler, L; Krümpelmann, U; Neuhaus, T; Heits, F; Einsele, H; Ritter, B; Bornhäuser, M; Schetelig, J; Thiede, C; Mohr, B; Schaich, M; Platzbecker, U; Schäfer-Eckart, K; Krämer, A; Berdel, W E; Serve, H; Ehninger, G; Schuler, U S

    2018-04-01

    The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve

  14. Generalized benign cutaneous reaction to cytarabine.

    PubMed

    Ruben, Beth S; Yu, Wesley Y; Liu, Fan; Truong, Sam V; Wang, Kevin C; Fox, Lindy P

    2015-11-01

    Cytarabine-induced toxicity manifests as various cutaneous morphologies. A generalized papular purpuric eruption has not been well described. We aimed to characterize a distinct cytarabine-related eruption. We reviewed all cases of cytarabine-related toxicity with papular purpuric eruptions or violaceous erythema at the University of California, San Francisco between 2006 and 2011. Sixteen cases were identified. The eruption began as erythematous papules that evolved into coalescing purpuric papules and plaques. It had affinity for intertriginous areas, neck, ears, and scalp. Pruritus was common, but no systemic complications were documented. Thirteen patients (81.3%) developed the eruption after completion of chemotherapy. Differential diagnosis often included viral exanthem (62.5%), drug eruption (50%), and vasculitis (37.5%). Histopathology was nonspecific but commonly demonstrated sparse lymphocytic infiltrates, spongiosis, and/or red cell extravasation. Importantly, the eruption was neither predicted by past cytarabine exposure nor predictive of future recurrence. This is a review of cases from a single institution. Observation was limited to acute hospitalization, however, charts were reviewed for subsequent reactions on rechallenge. The eruption described herein represents a specific skin-limited reaction to cytarabine. Awareness of its characteristic morphology, distribution, and timeline will aid in clinical diagnosis. Reassurance concerning its benign nature will prevent unnecessary intervention or cessation of chemotherapy. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Impact of novel polymorphisms related to cytotoxicity of cytarabine in the induction treatment of acute myeloid leukemia.

    PubMed

    Megías-Vericat, Juan E; Montesinos, Pau; Herrero, María J; Moscardó, Federico; Bosó, Virginia; Martínez-Cuadrón, David; Poveda, José L; Sanz, Miguel Á; Aliño, Salvador F

    2017-07-01

    Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy and toxicity was analyzed. Six of polymorphisms with clinical significance in the previous study [rs12036333, rs10758713, rs9883101, rs6550826, IRX2: rs2897047, mutated in colorectal cancers (MCC): rs7729269] were analyzed in a cohort of 225 adult patients at initial diagnosis of AML treated with an induction scheme of idarubicin plus cytarabine. The variant alleles of rs12036333 and rs10758713 confirmed the previous associations with lower survival rates. The minor alleles of rs9883101 and rs6550826 were also related to lower survival, in concordance with higher cytarabine-induced cytotoxicity observed in pediatric patients. However, discordant findings between AML adult and pediatric population were observed with IRX2 rs2897047, showing higher survival in heterozygous genotype carriers. The heterozygous genotype of MCC rs7729269 was associated with higher cytarabine-induced toxicities (renal, hepatic, lung, skin toxicities), whereas lower time to thrombocytopenia recovery was associated with the MCC rs7729269 minor allele. This study confirms the influence in survival rates of these polymorphisms in an adult AML population. Novel associations between MCC SNPs and cytarabine toxicities were reported and should be validated in prospective studies involving larger groups of patients.

  16. Chemical meningitis related to intra-CSF liposomal cytarabine.

    PubMed

    Durand, Bénédicte; Zairi, Fahed; Boulanger, Thomas; Bonneterre, Jacques; Mortier, Laurent; Le Rhun, Emilie

    2017-10-01

    Therapeutic options of leptomeningeal metastases include intra-cerebrospinal fluid (CSF) chemotherapy. Among intra-CSF agents, liposomal cytarabine has advantages but can induce specific toxicities. A BRAF-V600E-mutated melanoma leptomeningeal metastases patient, treated by dabrafenib and liposomal cytarabine, presented after the first injection of liposomal cytarabine with hyperthermia and headaches. Despite sterile CSF/blood analyses, extended intravenous antibiotics were given and the second injection was delayed. The diagnosis of chemical meningitis was finally made. Dose reduction and appropriate symptomatic treatment permitted the administration of 15 injections of liposomal cytarabine combined with dabrafenib. A confirmation of the diagnosis of chemical meningitis is essential in order (1) not to delay intra-CSF or systemic chemotherapy or (2) to limit the administration of unnecessary but potentially toxic antibiotics.

  17. Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption.

    PubMed

    Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin

    2016-09-10

    Cytarabine has a poor oral absorption due to its rapid deamination and poor membrane permeability. Bile acid transporters are highly expressed both in enterocytes and hepatocytes and to increase the oral bioavailability and investigate the potential application of cytarabine for liver cancers, a transporter- recognizing prodrug strategy was applied to design and synthesize four conjugates of cytarabine with cholic acid (CA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA) and ursodeoxycholic acid (UDCA). The anticancer activities against HepG2 cells were evaluated by MTT assay and the role of bile acid transporters during cellular transport was investigated in a competitive inhibition experiment. The in vitro and in vivo metabolic stabilities of these conjugates were studied in rat plasma and liver homogenates. Finally, an oral bioavailability study was conducted in rats. All the cholic acid-cytarabine conjugates (40μM) showed potent antiproliferative activities (up to 70%) against HepG2 cells after incubation for 48h. The addition of bile acids could markedly reduce the antitumor activities of these conjugates. The N(4)-ursodeoxycholic acid conjugate of cytarabine (compound 5) exhibited optimal stability (t1/2=90min) in vitro and a 3.9-fold prolonged half-life of cytarabine in vivo. More importantly, compound 5 increased the oral bioavailability 2-fold compared with cytarabine. The results of the present study suggest that the prodrug strategy based on the bile acid transporters is suitable for improving the oral absorption and the clinical application of cytarabine. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. ABCC4 Is a Determinant of Cytarabine-Induced Cytotoxicity and Myelosuppression.

    PubMed

    Drenberg, C D; Hu, S; Li, L; Buelow, D R; Orwick, S J; Gibson, A A; Schuetz, J D; Sparreboom, A; Baker, S D

    2016-02-01

    Resistance to cytarabine remains a major challenge in the treatment of acute myeloid leukemia (AML). Based on previous studies implicating ABCC4/MRP4 in the transport of nucleosides, we hypothesized that cytarabine is sensitive to ABCC4-mediated efflux, thereby decreasing its cytotoxic response against AML blasts. The uptake of cytarabine and its monophosphate metabolite was found to be facilitated in ABCC4-expressing vesicles and intracellular retention was significantly impaired by overexpression of human ABCC4 or mouse Abcc4 (P < 0.05). ABCC4 was expressed highly in AML primary blasts and cell lines, and cytotoxicity of cytarabine in cells was increased in the presence of the ABCC4 inhibitors MK571 or sorafenib, as well as after ABCC4 siRNA. In Abcc4-null mice, cytarabine-induced hematological toxicity was enhanced and ex vivo colony-forming assays showed that Abcc4-deficiency sensitized myeloid progenitors to cytarabine. Collectively, these studies demonstrate that ABCC4 plays a protective role against cytarabine-mediated insults in leukemic and host myeloid cells. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  19. Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML.

    PubMed

    Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

    2017-05-01

    We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3.

  20. Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML

    PubMed Central

    Malani, D; Murumägi, A; Yadav, B; Kontro, M; Eldfors, S; Kumar, A; Karjalainen, R; Majumder, M M; Ojamies, P; Pemovska, T; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Aittokallio, T; Kallioniemi, O

    2017-01-01

    We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3. PMID:27833094

  1. Palmar-plantar erythrodysesthesia syndrome following treatment with high-dose methotrexate or high-dose cytarabine.

    PubMed

    Karol, Seth E; Yang, Wenjian; Smith, Colton; Cheng, Cheng; Stewart, Clinton F; Baker, Sharyn D; Sandlund, John T; Rubnitz, Jeffrey E; Bishop, Michael W; Pappo, Alberto S; Jeha, Sima; Pui, Ching-Hon; Relling, Mary V

    2017-09-15

    Palmar-plantar erythrodysesthesia syndrome (PPES) is an uncommon side effect of high-dose cytarabine or methotrexate. Prior case reports of PPES have been limited, and the predisposing factors for the development of PPES remain unknown. A review of databases identified 22 patients (1.3%) who developed 39 episodes of PPES among 1720 patients after treatment with high-dose cytarabine or methotrexate. Symptoms lasted a mean of 6.4 days. Hands and feet were both involved in 68% of the initial episodes. Parenteral opioids were required for pain control by 27% of the patients. In comparison with the 1698 children treated with similar therapy, the children who developed PPES were older (mean age at diagnosis, 14.3 vs 7.7 years; P = 7.5 × 10 -7 ). The frequency of PPES was less common in patients receiving methotrexate alone (7 of 946 or 0.7%) versus cytarabine (7 of 205 or 3.4%; P = .005) but was not different for those receiving both high-dose methotrexate and cytarabine (8 of 569 or 1.4%; P = .32). Prolonged infusions of methotrexate were associated with less frequent PPES in comparison with rapid infusions (P = 1.5 × 10 -5 ), as was the co-administration of dexamethasone with cytarabine (P = 2.5 × 10 -6 ). Self-described race and sex were not associated with PPES. In a multivariate analysis, older age and high-dose cytarabine administration without dexamethasone remained associated with PPES (P = 1.1 × 10 -4 and P = .038, respectively). A genome-wide association study did not identify any associations with PPES meeting the genome-wide significance threshold, but top variants were enriched for skin expression quantitative trait loci, including rs11764092 in AUTS2 (P = 6.45 × 10 -5 ). These data provide new insight into the incidence of PPES as well as its risk factors. Cancer 2017;123:3602-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Protection of intestinal damage by pretreatment with cytarabine (cytosine arabinoside)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Phelps, T.A.; Blackett, N.M.

    The circumstances in which cytarabine (cytosine arabinoside) ''protects'' intestinal epithelial stem cells against radiation have been investigated. Special attention has been given to this protective effect with radiation doses in the clinically used range in order to determine whether the protective effect might be of use in radiotherapy. It has been shown that 12 hours after cytarabine the D/sub 0/ and extrapolation number are increased when large single doses of radiation are used. To determine the effect of cytarabine at lower doses, it is necessary to use a second irradiation as an ''assay'' dose. By this means it is shownmore » that there is more protection than can be accounted for by the change in D/sub 0/ and extrapolation number at the time of the first dose. Evidence is presented indicating that the rate of stem cell regeneration is not increased by cytarabine pretreatment. Finally, the relation between intestinal protection, bone marrow stem cell enhanced recovery and improved animal survival as a result of cytarabine pretreatment is discussed.« less

  3. Cytarabine-resistant leukemia cells are moderately sensitive to clofarabine in vitro.

    PubMed

    Yamauchi, Takahiro; Uzui, Kanako; Nishi, Rie; Shigemi, Hiroko; Ueda, Takanori

    2014-04-01

    Clofarabine is transported into leukemic cells via the equilibrative nucleoside transporters (hENT) 1 and 2 and the concentrative nucleoside transporter (hCNT) 3, then phosphorylated by deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) to an active triphosphate metabolite. Cytarabine uses hENT1 and dCK for its activation. We hypothesized that cytarabine-resistant leukemia cells retain sensitivity to clofarabine. Human myeloid leukemia HL-60 cells and cytarabine-resistant variant HL/ara-C20 cells were used in the present study. Despite 20-fold cytarabine resistance, the HL/ara-C20 cells exhibited only a 6-fold resistance to clofarabine compared to HL-60 cells. The intracellular concentration of the triphosphate metabolite of cytarabine was reduced to 1/10, and that of clofarabine was halved in the HL/ara-C20 cells. hENT1 and dCK were reduced, but hCNT3 and dGK were not altered in the HL/ara-C20 cells, which might contribute to their retained capability to produce intracellular triphosphate metabolite of clofarabine. Clofarabine was cytotoxic to leukemia cells that were resistant to cytarabine.

  4. Effects of cytarabine on activation of human T cells - cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic acid.

    PubMed

    Ersvaer, Elisabeth; Brenner, Annette K; Vetås, Kristin; Reikvam, Håkon; Bruserud, Øystein

    2015-05-02

    Cytarabine is used in the treatment of acute myeloid leukemia (AML). Low-dose cytarabine can be combined with valproic acid and all-trans retinoic acid (ATRA) as AML-stabilizing treatment. We have investigated the possible risk of immunotoxicity by this combination. We examined the effects of cytarabine combined with valproic acid and ATRA on in vitro activated human T cells, and we tested cytarabine at concentrations reached during in vivo treatment with high doses, conventional doses and low doses. T cells derived from blood donors were activated in vitro in cell culture medium alone or supplemented with ATRA (1 μM), valproic acid (500 or 1000 μM) or cytarabine (0.01-44 μM). Cell characteristics were assessed by flow cytometry. Supernatants were analyzed for cytokines by ELISA or Luminex. Effects on primary human AML cell viability and proliferation of low-dose cytarabine (0.01-0.5 μM) were also assessed. Statistical tests include ANOVA and Cluster analyses. Only cytarabine 44 μM had both antiproliferative and proapoptotic effects. Additionally, this concentration increased the CD4:CD8 T cell ratio, prolonged the expression of the CD69 activation marker, inhibited CD95L and heat shock protein (HSP) 90 release, and decreased the release of several cytokines. In contrast, the lowest concentrations (0.35 and 0.01 μM) did not have or showed minor antiproliferative or cytotoxic effects, did not alter activation marker expression (CD38, CD69) or the release of CD95L and HSP90, but inhibited the release of certain T cell cytokines. Even when these lower cytarabine concentrations were combined with ATRA and/or valproic acid there was still no or minor effects on T cell viability. However, these combinations had strong antiproliferative effects, the expression of both CD38 and CD69 was altered and there was a stronger inhibition of the release of FasL, HSP90 as well as several cytokines. Cytarabine (0.01-0.05 μM) showed a dose-dependent antiproliferative effect on

  5. Deoxycytidine kinase is downregulated under hypoxic conditions and confers resistance against cytarabine in acute myeloid leukaemia.

    PubMed

    Degwert, Nicole; Latuske, Emily; Vohwinkel, Gabi; Stamm, Hauke; Klokow, Marianne; Bokemeyer, Carsten; Fiedler, Walter; Wellbrock, Jasmin

    2016-09-01

    Leukaemia initiating cells reside within specialised niches in the bone marrow where they undergo complex interactions with different stromal cell types. The bone marrow niche is characterised by a low oxygen content resulting in high expression of hypoxia-inducible factor 1 α in leukaemic cells conferring a negative prognosis to patients with acute myeloid leukaemia (AML). In the current study, we investigated the impact of hypoxic vs. normoxic conditions on the sensitivity of AML cell lines and primary AML blasts to cytarabine. AML cells cultured under 6% oxygen were significantly more resistant against cytarabine compared to cells cultured under normoxic conditions in proliferation and colony-formation assays. Interestingly upon cultivation under hypoxia, the expression of the cytarabine-activating enzyme deoxycytidine kinase was downregulated in all analysed AML cell lines and primary AML samples representing a possible mechanism for resistance to chemotherapy. Furthermore, the downregulation of deoxycytidine kinase could be associated with hypoxia-inducible factor 1 α as treatment with its inhibitor BAY87-2243 hampered the downregulation of deoxycytidine kinase expression under hypoxic conditions. In conclusion, our data reveal that hypoxia-induced downregulation of deoxycytidine kinase represents one stroma-cell-independent mechanism of drug resistance to cytarabine in acute myeloid leukaemia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Activity of the Multikinase Inhibitor Sorafenib in Combination With Cytarabine in Acute Myeloid Leukemia

    PubMed Central

    Hu, Shuiying; Niu, Hongmei; Inaba, Hiroto; Orwick, Shelley; Rose, Charles; Panetta, John C.; Yang, Shengping; Pounds, Stanley; Fan, Yiping; Calabrese, Christopher; Rehg, Jerold E.; Campana, Dario; Rubnitz, Jeffrey E.

    2011-01-01

    Background Acute myeloid leukemia (AML) is a genetically heterogeneous cancer that frequently exhibits aberrant kinase signaling. We investigated a treatment strategy combining sorafenib, a multikinase inhibitor with limited single-agent activity in AML, and cytarabine, a key component of AML chemotherapy. Methods Using 10 human AML cell lines, we determined the effects of sorafenib (10 μM) on antileukemic activity by measuring cell viability, proliferation, ERK1/2 signaling, and apoptosis. We also investigated the effects of sorafenib treatment on the accumulation of cytarabine and phosphorylated metabolites in vitro. A human equivalent dose of sorafenib in nontumor-bearing NOD-SCID-IL2Rγnull mice was determined by pharmacokinetic studies using high performance liquid chromatography with tandem mass spectrometric detection, and steady-state concentrations were estimated by the fit of a one-compartment pharmacokinetic model to concentration–time data. The antitumor activity of sorafenib alone (60 mg/kg) twice daily, cytarabine alone (6.25 mg/kg administered intraperitoneally), or sorafenib once or twice daily plus cytarabine was evaluated in NOD-SCID-IL2Rγnull mice bearing AML xenografts. Results Sorafenib at 10 μM inhibited cell viability, proliferation and ERK1/2 signaling, and induced apoptosis in all cell lines studied. Sorafenib also increased the cellular accumulation of cytarabine and metabolites resulting in additive to synergistic antileukemic activity. A dose of 60 mg/kg in mice produced a human equivalent sorafenib steady-state plasma exposure of 10 μM. The more dose-intensive twice-daily sorafenib plus cytarabine (n = 15) statistically significantly prolonged median survival in an AML xenograft model compared with sorafenib once daily plus cytarabine (n = 12), cytarabine alone (n = 26), or controls (n = 27) (sorafenib twice daily plus cytarabine, median survival = 46 days; sorafenib once daily plus cytarabine, median survival = 40 days

  7. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine; Jonsson, Olafur Gisli; Taskinen, Mervi; Abrahamsson, Jonas; Vettenranta, Kim; Åsberg, Ann; Risteli, Juha; Heldrup, Jesper; Schmiegelow, Kjeld

    2016-11-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6/27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower extremity sensory pain in 1 liposomal cytarabine-treated patient, no permanent adverse neurological sequelae were observed. In intention-to-treat analysis, projected 5-year event-free survival (pEFS-5y) was borderline higher for patients in the liposomal cytarabine arm compared with the TIT arm (1.0 vs. 0.69, P=0.046). However, pEFS-5y and projected 5-year relapse-free survival did not differ signficantly between patients treated with liposomal cytarabine or TIT (1.0 vs. 0.73, P=0.10; 1.0 vs. 0.76, P=0.12). Larger prospective trials are needed to explore whether liposomal cytarabine should be used as first-line prevention of relapse.

  8. Daunorubicin Hydrochloride and Cytarabine Liposome

    Cancer.gov

    This page contains brief information about daunorubicin hydrochloride and cytarabine liposome and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  9. Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats.

    PubMed

    Hernández García, Ernestina; Osnaya Brizuela, Norma; Valenzuela Peraza, Armando; Calderón Guzmán, David; Ortiz Herrera, Maribel; Juárez Olguín, Hugo; Barragán Mejía, Gerardo; Santamaría Del Ángel, Daniel; Rojas Ochoa, Alberto

    2018-02-13

    The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to measure levels of dopamine, lipid peroxidation (TBARS), serotonin metabolite (5-HIAA), Na+, K+ ATPase activity, and glutathione (GSH), using validated methods. Sweeteners increased the glucose in animals that received cytarabine. Dopamine increased in cortex and decreased in striatum of animals that received stevia alone and combined with cytarabine. 5-HIAA decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined. GSH increased in animals that received sweeteners and decreased with cytarabine. Lipoperoxidation decreased in groups that received sweeteners and cytarabine. Histopathological changes revealed marked degeneration of neuronal cells in animals treated with cytarabine. These results show that sweeteners as stevia or splenda may lead to the onset of unfavorable changes in dopamine and 5-HIAA. Antioxidant effects may be involved. Besides, histological changes revealed marked lesions of neuronal cells in experimental animals treated with cytarabine.

  10. Cytarabine syndrome despite corticosteroid premedication in an adult undergoing induction treatment for acute myelogenous leukemia.

    PubMed

    Jirasek, Matthew A; Herrington, Jon D

    2016-12-01

    Cytarabine syndrome is a rare clinical condition characterized by fever, malaise, myalgia, arthralgia, and/or rash that occurs after receipt of cytarabine. Our patient developed fever, malaise, and diffuse body pain shortly following cytarabine initiation despite receiving prophylactic dexamethasone. The patient's discomfort was treated with intravenous morphine and her other symptoms were controlled with a higher dose of dexamethasone. Although the exact cause is not fully understood, cytarabine syndrome is hypothesized to be an immune-mediated response following cytarabine-induced apoptosis that results in a rapid increase in proinflammatory cytokines. While there is no standard therapy for cytarabine syndrome, corticosteroids appear to play a role in the treatment and prevention of the condition by suppressing the proinflammatory response. Since our case describes the development of cytarabine syndrome despite dexamethasone, clinicians should monitor for this adverse event if patients begin exhibiting characteristics of this syndrome. © The Author(s) 2015.

  11. The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates.

    PubMed

    Pola, R; Janoušková, O; Etrych, T

    2016-10-20

    Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropa-noyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl-phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and beta-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine.

  12. Systemic effects of low-dose dopamine during administration of cytarabine.

    PubMed

    Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

    2017-09-01

    Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

  13. Pharmacokinetics and toxicity of intrathecal liposomal cytarabine in children and adolescents following age-adapted dosing.

    PubMed

    Peyrl, Andreas; Sauermann, Robert; Chocholous, Monika; Azizi, Amedeo A; Jäger, Walter; Höferl, Martina; Slavc, Irene

    2014-02-01

    Assessment of the optimal drug dose for intrathecal therapy in children is challenging because of the non-linear increase in cerebrospinal fluid (CSF) volume throughout childhood and potential differences in the elimination rate in children versus adults. The present study was designed to prospectively collect pharmacokinetic and safety data on age-adapted intrathecal liposomal cytarabine in children aged >3 years. Sixteen patients with malignant brain tumours were included in the study. Children aged 3-10 years received liposomal cytarabine 35 mg with concomitant dexamethasone, and those aged >10 years received 50 mg. Serial CSF and plasma samples were collected before administration and 1 h, 12 h, 24 h, 1 week and 2 weeks post-dosing. CSF was analysed for free and encapsulated cytarabine, and plasma was analysed for free cytarabine. The average elimination half-life values in children aged 3-10 years and in those aged >10 years, treated with liposomal cytarabine 35 mg and 50 mg, respectively, were 40.9 and 43.7 h for free cytarabine and 31.5 and 36.4 h for encapsulated cytarabine in CSF. Although these values were lower than those previously reported, cytarabine concentrations exceeded the cytotoxic threshold of 0.1 mg/L in all patients until 1 week post-intraventricular administration. Cytarabine concentrations in plasma were negligible. In general, liposomal cytarabine was well tolerated, with relevant but manageable toxicities. Liposomal cytarabine in doses of 35 mg for children aged 3-10 years and 50 mg for older patients shows sufficient drug exposure for at least 1 week and appears to be well tolerated.

  14. Effects of Selective Checkpoint Kinase 1 Inhibition on Cytarabine Cytotoxicity in Acute Myelogenous Leukemia Cells in Vitro

    PubMed Central

    Schenk, Erin L.; Koh, Brian D.; Flatten, Karen S.; Peterson, Kevin L.; Parry, David; Hess, Allan D.; Smith, B. Douglas; Karp, Judith E.; Karnitz, Larry M.; Kaufmann, Scott H.

    2012-01-01

    Purpose Previous studies have demonstrated that the replication checkpoint, which involves the kinases ATR and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical AML during cytarabine infusion in vivo and then assessed the impact of combining cytarabine with the recently described Chk1 inhibitor SCH 900776 in vitro. Experimental design AML marrow aspirates harvested before and during cytarabine infusion were examined by immunoblotting. Human AML lines treated with cytarabine in the absence or presence of SCH 900776 were assayed for checkpoint activation by immunoblotting, nucleotide incorporation into DNA and flow cytometry. Long-term effects in AML lines, clinical AML isolates, and normal myeloid progenitors were assayed using clonogenic assays. Results Immunoblotting demonstrated increased Chk1 phosphorylation, a marker of checkpoint activation, in over half of Chk1-containing AMLs after 48 h of cytarabine infusion. In human AML lines, SCH 900776 not only disrupted cytarabine-induced Chk1 activation and S phase arrest, but also markedly increased cytarabine-induced apoptosis. Clonogenic assays demonstrated that SCH 900776 enhanced the anti-proliferative effects of cytarabine in AML cell lines and clinical AML samples at concentrations that had negligible impact on normal myeloid progenitors. Conclusions These results not only provide evidence for cytarabine-induced S phase checkpoint activation in AML in the clinical setting, but also show that a selective Chk1 inhibitor can overcome the S phase checkpoint and enhance the cytotoxicity of cytarabine. Accordingly, further investigation of the cytarabine/SCH 900776 combination in AML appears warranted. PMID:22869869

  15. Novel liver-specific cholic acid-cytarabine conjugates with potent antitumor activities: Synthesis and biological characterization

    PubMed Central

    Chen, Dan-qi; Wang, Xin; Chen, Lin; He, Jin-xue; Miao, Ze-hong; Shen, Jing-kang

    2011-01-01

    Aim: Cytarabine is an efficient anticancer agent for acute myelogenous leukemia, but with short plasma half-life and rapid deamination to its inactive metabolite. The aim of this study was to design and synthesize novel cholic acid-cytarabine conjugates to improve its pharmacokinetic parameters. Methods: The in vitro stability of novel cholic acid-cytarabine conjugates was investigated in simulated gastric and intestinal fluid, mouse blood and liver homogenate using HPLC. The portacaval samples of the conjugates were examined in male Sprague-Dawley rats using LC/MS, and in vivo distribution was examined in male Kunming mice using LC/MS. Antitumor activities were tested in HL60 cells using MTT assay. Results: Cholic acid-cytarabine compounds with four different linkers were designed and synthesized. All the four cholic acid-cytarabine conjugates could release cytarabine when incubated with the simulated gastric and intestinal fluid, mouse blood and liver homogenate. The conjugates 6, 12, and 16 were present in the portacaval samples, whereas the conjugate 7 was not detected. The conjugates 6 and 16 showed high specificity in targeting the liver (liver target index 34.9 and 16.3, respectively) and good absorption in vivo, as compared with cytarabine. In cytarabine-sensitive HL60 cells, the conjugates 6, 12, and 16 retained potent antitumor activities. Conclusion: Three novel cholic acid-cytarabine conjugates with good liver-targeting properties and absorption were obtained. Further optimization of the conjugates is needed in the future. PMID:21516131

  16. Safety of inadvertent administration of overdose of intrathecal Cytarabine in a pediatric patient.

    PubMed

    Al Omar, Suha; Amayiri, Nisreen; Madanat, Faris

    2015-10-01

    To describe a medication error of intrathecal Cytarabine overdose that was managed conservatively with no apparent toxicities. An 11-year-old girl was diagnosed with bone marrow relapsed precursor B-cell acute lymphoblastic leukemia. According to her chemotherapy protocol, she was started on triple intrathecal chemotherapy consisting of Methotrexate, Cytarabine and Hydrocortisone on day 1 of the protocol. After the intrathecal therapy being administered to the patient, the pharmacist who checked the medication realized that the wrong formulation of Cytarabine was used to prepare the intrathecal therapy; this error resulted in five times overdose of Cytarabine. The patient was then managed conservatively without cerebrospinal fluid exchange. Our patient remained clinically and neurologically stable without apparent toxicities and was discharged safely from hospital. Supportive care without the need for invasive procedures such as cerebrospinal fluid exchange may be adequate for managing intrathecal Cytarabine overdose. © The Author(s) 2014.

  17. Evaluation of Cytarabine Against Ewing Sarcoma Xenografts by the Pediatric Preclinical Testing Program

    PubMed Central

    Houghton, Peter J.; Morton, Christopher L.; Kang, Min; Reynolds, C. Patrick; Billups, Catherine A.; Favours, Edward; Payne-Turner, Debbie; Tucker, Chandra; Smith, Malcolm A.

    2015-01-01

    Treatment with the nucleoside analog cytarabine has been shown to mimic changes in gene expression associated with down-regulation of the EWS-FLI1 oncogene in Ewing sarcoma cell lines, selectively inhibit their growth in vitro, and cause tumor regression in athymic nude mice. For this report cytarabine was studied in vitro against a panel of 23 pediatric cancer cell lines and in vivo against 6 Ewing sarcoma xenografts. Acute lymphoblastic leukemia cell lines were the most sensitive to cytarabine in vitro (median IC50 9 nM), while Ewing sarcoma cell lines showed intermediate sensitivity (median IC50 232 nM). Cytarabine at a dose of 150 mg/kg administered daily 5× failed to significantly inhibit growth of five xenograft models, but reduced growth rate of the A673 xenograft by 50%. Cytarabine shows no differential in vitro activity against Ewing sarcoma cell lines and is ineffective in vivo against Ewing sarcoma xenografts at the dose and schedule studied. PMID:20979180

  18. The hematopoietic tumor suppressor interferon regulatory factor 8 (IRF8) is upregulated by the antimetabolite cytarabine in leukemic cells involving the zinc finger protein ZNF224, acting as a cofactor of the Wilms' tumor gene 1 (WT1) protein.

    PubMed

    Montano, Giorgia; Ullmark, Tove; Jernmark-Nilsson, Helena; Sodaro, Gaetano; Drott, Kristina; Costanzo, Paola; Vidovic, Karina; Gullberg, Urban

    2016-01-01

    The transcription factor interferon regulatory factor-8 (IRF8) is highly expressed in myeloid progenitors, while most myeloid leukemias show low or absent expression. Loss of IRF8 in mice leads to a myeloproliferative disorder, indicating a tumor-suppressive role of IRF8. The Wilms tumor gene 1 (WT1) protein represses the IRF8-promoter. The zinc finger protein ZNF224 can act as a transcriptional co-factor of WT1 and potentiate the cytotoxic response to the cytostatic drug cytarabine. We hypothesized that cytarabine upregulates IRF8 and that transcriptional control of IRF8 involves WT1 and ZNF224. Treatment of leukemic K562 cells with cytarabine upregulated IRF8 protein and mRNA, which was correlated to increased expression of ZNF224. Knock down of ZNF224 with shRNA suppressed both basal and cytarabine-induced IRF8 expression. While ZNF224 alone did not affect IRF8 promoter activity, ZNF224 partially reversed the suppressive effect of WT1 on the IRF8 promoter, as judged by luciferase reporter experiments. Coprecipitation revealed nuclear binding of WT1 and ZNF224, and by chromatin immunoprecipitation (ChIP) experiments it was demonstrated that WT1 recruits ZNF224 to the IRF8 promoter. We conclude that cytarabine-induced upregulation of the IRF8 in leukemic cells involves increased levels of ZNF224, which can counteract the repressive activity of WT1 on the IRF8-promoter. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Inhibition of mTOR-Dependent Autophagy Sensitizes Leukemic Cells to Cytarabine-Induced Apoptotic Death

    PubMed Central

    Arsikin, Katarina; Mircic, Aleksandar; Suzin-Zivkovic, Violeta; Perovic, Vladimir; Bogdanovic, Andrija; Paunovic, Verica; Markovic, Ivanka; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2014-01-01

    The present study investigated the role of autophagy, a cellular self-digestion process, in the cytotoxicity of antileukemic drug cytarabine towards human leukemic cell lines (REH, HL-60, MOLT-4) and peripheral blood mononuclear cells from leukemic patients. The induction of autophagy was confirmed by acridine orange staining of intracellular acidic vesicles, electron microscopy visualization of autophagic vacuoles, as well as by the increase in autophagic proteolysis and autophagic flux, demonstrated by immunoblot analysis of p62 downregulation and LC3-I conversion to autophagosome-associated LC3-II in the presence of proteolysis inhibitors, respectively. Moreover, the expression of autophagy-related genes Atg4, Atg5 and Atg7 was stimulated by cytarabine in REH cells. Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase. Cytarabine had no effect on the activation of mTOR inhibitor AMP-activated protein kinase. Leucine, an mTOR activator, reduced both cytarabine-induced autophagy and cytotoxicity. Accordingly, pharmacological downregulation of autophagy with bafilomycin A1 and chloroquine, or RNA interference-mediated knockdown of LC3β or p62, markedly increased oxidative stress, mitochondrial depolarization, caspase activation and subsequent DNA fragmentation and apoptotic death in cytarabine-treated REH cells. Cytarabine also induced mTOR-dependent cytoprotective autophagy in HL-60 and MOLT-4 leukemic cell lines, as well as primary leukemic cells, but not normal leukocytes. These data suggest that the therapeutic efficiency of cytarabine in leukemic patients could be increased by the inhibition of the mTOR-dependent autophagic response. PMID:24714637

  20. Inhibition of mTOR-dependent autophagy sensitizes leukemic cells to cytarabine-induced apoptotic death.

    PubMed

    Bosnjak, Mihajlo; Ristic, Biljana; Arsikin, Katarina; Mircic, Aleksandar; Suzin-Zivkovic, Violeta; Perovic, Vladimir; Bogdanovic, Andrija; Paunovic, Verica; Markovic, Ivanka; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

    2014-01-01

    The present study investigated the role of autophagy, a cellular self-digestion process, in the cytotoxicity of antileukemic drug cytarabine towards human leukemic cell lines (REH, HL-60, MOLT-4) and peripheral blood mononuclear cells from leukemic patients. The induction of autophagy was confirmed by acridine orange staining of intracellular acidic vesicles, electron microscopy visualization of autophagic vacuoles, as well as by the increase in autophagic proteolysis and autophagic flux, demonstrated by immunoblot analysis of p62 downregulation and LC3-I conversion to autophagosome-associated LC3-II in the presence of proteolysis inhibitors, respectively. Moreover, the expression of autophagy-related genes Atg4, Atg5 and Atg7 was stimulated by cytarabine in REH cells. Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase. Cytarabine had no effect on the activation of mTOR inhibitor AMP-activated protein kinase. Leucine, an mTOR activator, reduced both cytarabine-induced autophagy and cytotoxicity. Accordingly, pharmacological downregulation of autophagy with bafilomycin A1 and chloroquine, or RNA interference-mediated knockdown of LC3β or p62, markedly increased oxidative stress, mitochondrial depolarization, caspase activation and subsequent DNA fragmentation and apoptotic death in cytarabine-treated REH cells. Cytarabine also induced mTOR-dependent cytoprotective autophagy in HL-60 and MOLT-4 leukemic cell lines, as well as primary leukemic cells, but not normal leukocytes. These data suggest that the therapeutic efficiency of cytarabine in leukemic patients could be increased by the inhibition of the mTOR-dependent autophagic response.

  1. Severe Cerebral Vasospasm and Childhood Arterial Ischemic Stroke After Intrathecal Cytarabine.

    PubMed

    Tibussek, Daniel; Natesirinilkul, Rungrote; Sun, Lisa R; Wasserman, Bruce A; Brandão, Leonardo R; deVeber, Gabrielle

    2016-02-01

    We report on 2 patients who developed widespread cerebral vasospasm and arterial ischemic strokes (AIS) after application of intrathecal (IT) cytarabine. In a 3-year-old child with acute lymphoblastic leukemia (ALL), left leg weakness, hyperreflexia, and clonus were noted 4 days after her first dose of IT cytarabine during the induction phase of her chemotherapy. Cerebral MRI revealed multiple acute cerebral ischemic infarcts and widespread cerebral vasospasm. A 5-year-old girl complained of right arm and leg pain and began limping 11 days after IT cytarabine. Symptoms progressed to right dense hemiplegia, left gaze deviation, headache, and speech arrest. MRI revealed 2 large cortical areas of diffusion restriction in the right frontal and left parietal lobes. Cerebral magnetic resonance angiography (MRA) showed irregular narrowing affecting much of the intracranial arterial circulation. Although the first child fully recovered from her neurologic symptoms, the second patient had persistent hemiplegia on follow-up. Including this report, there are now 4 pediatric ALL cases of severe cerebral vasospasm and AIS in the context of IT cytarabine administration, strongly suggesting a true association. Differential diagnosis and management issues are discussed. Along with the more widespread use of MRI and MRA, the true frequency of this severe adverse effect will become clearer in future. For any child with neurologic symptoms within hours or days of receiving IT cytarabine, a low threshold for cerebral imaging with MRI and MRA is recommended. Copyright © 2016 by the American Academy of Pediatrics.

  2. FLT3 is implicated in cytarabine transport by human equilibrative nucleoside transporter 1 in pediatric acute leukemia.

    PubMed

    Català, Albert; Pastor-Anglada, Marçal; Caviedes-Cárdenas, Liska; Malatesta, Roberta; Rives, Susana; Vega-García, Nerea; Camós, Mireia; Fernández-Calotti, Paula

    2016-08-02

    FLT3 abnormalities are negative prognostic markers in acute leukemia. Infant leukemias are a subgroup with frequent MLL (KMT2A) rearrangements, FLT3 overexpression and high sensitivity to cytarabine, but dismal prognosis. Cytarabine is transported into cells by Human Equilibrative Nucleoside Transporter-1 (hENT1, SLC29A1), but the mechanisms that regulate hENT1 in acute leukemia have been scarcely studied.We explored the expression and functional link between FLT3 and main cytarabine transporters in 50 pediatric patients diagnosed with acute lymphoblastic leukemia and MLL rearrangement (ALL-MLL+) and other subtypes of leukemia, and in leukemia cell lines.A significant positive correlation was found between FLT3 and hENT1 expression in patients. Cytarabine uptake into cells was mediated mainly by hENT1, hENT2 and hCNT1. hENT1-mediated uptake of cytarabine was transiently abolished by the FLT3 inhibitor PKC412, and this effect was associated with decreased hENT1 mRNA and protein levels. Noticeably, the cytotoxicity of cytarabine was lower when cells were first exposed to FLT3 inhibitors (PKC412 or AC220), probably due to decreased hENT1 activity, but we observed a higher cytotoxic effect if FLT3 inhibitors were administered after cytarabine.FLT3 regulates hENT1 activity and thereby affects cytarabine cytotoxicity. The sequence of administration of cytarabine and FLT3 inhibitors is important to maintain their efficacy.

  3. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia.

    PubMed

    Azevedo, M C; Velloso, E D R P; Buccheri, V; Chamone, D A F; Dorlhiac-Llacer, P E

    2015-02-01

    In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

  4. Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

    PubMed Central

    Azevedo, M.C.; Velloso, E.D.R.P.; Buccheri, V.; Chamone, D.A.F.; Dorlhiac-Llacer, P.E.

    2014-01-01

    In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival. PMID:25517921

  5. Genipin-modified gelatin nanocarriers as swelling controlled drug delivery system for in vitro release of cytarabine.

    PubMed

    Khan, Huda; Shukla, R N; Bajpai, A K

    2016-04-01

    The aim of the present investigation was to design biocompatible gelatin nanoparticles, capable of releasing the cytarabine drug in a controllable way by regulating the extent of swelling of nanoparticles. In order to achieve the proposed objectives, gelatin (Type A, derived from acid cured tissue) was modified by crosslinking with genipin and nanoparticles of crosslinked gelatin were prepared using single water in oil (W/O) emulsion technique. The nanoparticles were characterized by techniques like FTIR, SEM, TEM, particles size analysis, and surface potential measurements. The nanoparticle chemical architecture was found to influence drug-releasing capacity. The influence of experimental conditions such as pH and simulated physiological fluids as the release medium was also investigated on the release profiles of cytarabine. It is possible to fabricate high-performance materials, by designing of controlled size gelatin nanoparticles with good biocompatible properties along with desired drug release profiles. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Panobinostat Enhances Cytarabine and Daunorubicin Sensitivities in AML Cells through Suppressing the Expression of BRCA1, CHK1, and Rad51

    PubMed Central

    Edwards, Holly; Caldwell, J. Timothy; Chen, Wei; Inaba, Hiroto; Xu, Xuelian; Buck, Steven A.; Taub, Jeffrey W.; Baker, Sharyn D.; Ge, Yubin

    2013-01-01

    Acute myeloid leukemia (AML) remains a challenging disease to treat and urgently requires new therapies to improve its treatment outcome. In this study, we investigated the molecular mechanisms underlying the cooperative antileukemic activities of panobinostat and cytarabine or daunorubicin (DNR) in AML cell lines and diagnostic blast samples in vitro and in vivo. Panobinostat suppressed expression of BRCA1, CHK1, and RAD51 in AML cells in a dose-dependent manner. Further, panobinostat significantly increased cytarabine- or DNR-induced DNA double-strand breaks and apoptosis, and abrogated S and/or G2/M cell cycle checkpoints. Analogous results were obtained by shRNA knockdown of BRCA1, CHK1, or RAD51. Cotreatment of NOD-SCID-IL2Rγnull mice bearing AML xenografts with panobinostat and cytarabine significantly increased survival compared to either cytarabine or panobinostat treatment alone. Additional studies revealed that panobinostat suppressed the expression of BRCA1, CHK1, and RAD51 through downregulation of E2F1 transcription factor. Our results establish a novel mechanism underlying the cooperative antileukemic activities of these drug combinations in which panobinostat suppresses expression of BRCA1, CHK1, and RAD51 to enhance cytarabine and daunorubicin sensitivities in AML cells. PMID:24244429

  7. Outcomes of Substituting Oral Fludarabine for Intravenous Fludarabine in Combination with Cytarabine and Filgrastim for Treatment of Primary Refractory or Relapsed Acute Leukemias.

    PubMed

    Demichelis-Gómez, Roberta; Crespo-Solís, Erick; Pérez-Jacobo, Luis Fernando; Valencia-Rocha, Ubaldo Rafael; Rosas-López, Adriana

    2015-01-01

    Treatment of relapsed/refractory acute myeloid or lymphoid leukemia consists of salvage chemotherapy followed by allogeneic hematopoietic stem-cell transplantation. Intravenous fludarabine, cytarabine, and filgrastim is an effective regimen in this setting. In view of the lack of availability of intravenous fludarabine in Mexico from 2009-2013, we substituted an equivalent oral fludarabine dose (40 mg) for the intravenous formulation. This is a retrospective comparison of the toxicity and effectiveness of oral fludarabine, cytarabine, and filgrastim versus intravenous fludarabine, cytarabine and filgrastim. A total of 44 patients with relapsed/refractory acute myeloid leukemia or acute lymphoid leukemia treated in an academic medical center from 2005-2013 with oral fludarabine, cytarabine and filgrastim (21 patients) or intravenous fludarabine, cytarabine and filgrastim (23 patients) were included in the analysis. There was a trend towards a higher complete remission rate and a longer overall survival following intravenous fludarabine, cytarabine, and filgrastim as compared with oral fludarabine, cytarabine, and filgrastim: complete remission rates 39.1 vs. 23.8% (p = 0.342) and overall survival 6.14 vs. 10.78 months (p = 0.363), respectively. A higher incidence of neutropenic fever (100 vs. 76.2%; p = 0.019) and septic shock (34.8 vs. 0%; p = 0.003) and a longer hospitalization (26.8 vs. 19.4 days; p = 0.046) were observed with intravenous fludarabine, cytarabine, and filgrastim. In multivariate analysis, factors associated with a shorter survival were septic shock (HR: 3.93; 95% CI: 1.67-9.25; p = 0.002) and a higher number of previous treatments (HR: 2.5; 95% CI: 1.26-4.99; p = 0.009). Complete remission was associated with better survival (HR: 0.18; 95% CI: 0.08-0.44; p < 0.001). Further studies are needed to determine the optimal dose and timing of oral fludarabine when given as part of the fludarabine, cytarabine, and filgrastim regimen for relapsed

  8. Effects of cholesterol concentration on the interaction of cytarabine with lipid membranes: a molecular dynamics simulation study.

    PubMed

    Karami, Leila; Jalili, Seifollah

    2015-01-01

    Liposomal cytarabine, DepoCyt, is a chemotherapy agent which is used in cancer treatment. This form of cytarabine has more efficacy and fewer side effects relative to the other forms. Since DepoCyt contains the cytarabine encapsulated within phosphatidylcholine and the sterol molecules, we modeled dioleoylphosphatidylcholine (DOPC)/cholesterol bilayer membrane as a carrier for cytarabine to study drug-bilayer interactions. For this purpose, we performed a series of united-atom molecular dynamics (MD) simulations for 25 ns to investigate the interactions between cytarabine and cholesterol-containing DOPC lipid bilayers. Only the uncharged form of cytarabine molecule was investigated. In this study, different levels of the cholesterol content (0, 20, and 40%) were used. MD simulations allowed us to determine dynamical and structural properties of the bilayer membrane and to estimate the preferred location and orientation of the cytarabine molecule inside the bilayer membrane. Properties such as membrane thickness, area per lipid, diffusion coefficient, mass density, bilayer packing, order parameters, and intermolecular interactions were examined. The results show that by increasing the cholesterol concentration in the lipid bilayers, the bilayer thickness increases and area per lipid decreases. Moreover, in accordance with the experiments, our calculations show that cholesterol molecules have ordering effect on the hydrocarbon acyl chains. Furthermore, the cytarabine molecule preferentially occupies the polar region of the lipid head groups to form specific interactions (hydrogen bonds). Our results fully support the experimental data. Our finding about drug-bilayer interaction is crucial for the liposomal drug design.

  9. Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi’s Sarcoma-Associated Herpesvirus Latent and Lytic Replications

    PubMed Central

    Gruffaz, Marion; Zhou, Shenghua; Vasan, Karthik; Rushing, Teresa; Michael, Qing Liu; Lu, Chu

    2018-01-01

    ABSTRACT Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically linked to primary effusion lymphoma (PEL), an aggressive and nontreatable malignancy commonly found in AIDS patients. In this study, we performed a high-throughput screening of 3,731 characterized compounds and identified cytarabine, approved by the FDA for treating numerous types of cancer, as a potent inhibitor of KSHV-induced PEL. We showed the high efficacy of cytarabine in the growth inhibition of various PEL cells by inducing cell cycle arrest and apoptosis. Cytarabine inhibited host DNA and RNA syntheses and therefore induced cellular cytotoxicity. Furthermore, cytarabine inhibited viral DNA and RNA syntheses and induced the rapid degradation of KSHV major latent protein LANA (latency-associated nuclear antigen), leading to the suppression of KSHV latent replication. Importantly, cytarabine effectively inhibited active KSHV replication and virion production in PEL cells. Finally, cytarabine treatments not only effectively inhibited the initiation and progression of PEL tumors but also induced regression of grown PEL tumors in a xenograft mouse model. Altogether, our study has identified cytarabine as a novel therapeutic agent for treating PEL as well as eliminating KSHV persistent infection. PMID:29739902

  10. Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

    PubMed

    Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

    2018-05-02

    Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Stability of four standardized preparations of methotrexate, cytarabine, and hydrocortisone for intrathecal use.

    PubMed

    Olmos-Jiménez, Raquel; Espuny-Miró, Alberto; Díaz-Carrasco, María Sacramento; Fernández-Varón, Emilio; Valderrey-Pulido, Manuel; Cárceles-Rodríguez, Carlos

    2016-10-01

    Intrathecal administration of methotrexate, cytarabine, and hydrocortisone is commonly used to treat and prevent central nervous system involvement in leukemias and lymphomas. The use of intrathecal solutions with pH and osmolarity values close to physiologic range of CSF (pH 7.31-7.37, osmolarity 281-306 mOsm/kg) and standardization of the methotrexate, cytarabine, and hydrocortisone doses in children and adults based on age is highly recommended. Stability studies of standardized intrathecal mixtures under these conditions have not yet been published. The purpose of this study was to evaluate the physical and chemical stabilities of four standardized mixtures of methotrexate, cytarabine, and hydrocortisone stored at 2-8℃ and 25℃ up to 7 days after preparation. Four different standardized intrathecal mixtures were prepared and stored at 2-8℃ and 25℃ and protected from light. Triplicate samples were taken at different times and precipitation, appearance, color, pH, and osmolarity were analyzed. Methotrexate, cytarabine, and hydrocortisone concentrations were measured using a modified high-performance liquid chromatography method. No variation greater than 10% of the initial concentration of methotrexate, cytarabine, and hydrocortisone was observed in any of the four standardized mixtures for the 7 days of study when stored at 2-8℃ and 25℃ and protected from light. The osmolarity of the four preparations was within the physiologic range of CSF for 7 days at both 2-8℃ and 25℃. The pH values close to the physiologic range of CSF were stable for 48 h at 25℃ and for 120 h at 2-8℃. Triple intrathecal standardized preparations of methotrexate, cytarabine, and hydrocortisone sodium phosphate are physically and chemically stable at 25℃ for 48 h and at 2-8℃ for 5 days. © The Author(s) 2015.

  12. Oleic Acid Protects Against Oxidative Stress Exacerbated by Cytarabine and Doxorubicin in Rat Brain.

    PubMed

    Guzmán, David Calderón; Brizuela, Norma Osnaya; Herrera, Maribel Ortíz; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; Mejía, Gerardo Barragán

    2016-01-01

    The objective of this study was to analyze the effect of doxorubicin and cytarabine on biogenic amines and oxidative biomarkers in the brain of rats treated with oleic acid. Thirty-six Wistar rats distributed in 6 groups, were treated as follows: group 1 (control), NaCl 0.9%; group 2 doxorubicin (1mg/kg); group 3 cytarabine (70mg /kg); group 4 oleic acid (1500μl/kg); group 5 doxorubicin + oleic acid; group 6 cytarabine + oleic acid. All compounds were administered intraperitoneally for 5 days. The Rats were sacrificed after receiving the last administration and their brains were dissected in cortex, hemispheres, and cerebellum/medulla oblongata. Blood samples were obtained on sacrifice to assess the levels of glucose and triglycerides. In each brain region, lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolites (5-HIAA) and dopamine were measured using validated methods. Cytarabine decreased the levels of dopamine, TBARS, GSH, H2O2 and ATPase in all regions. Doxorubicin combined with oleic acid increased the levels of GSH in cortex, and decreased ATPase in cerebellum/medulla oblongata. These results suggest that the reduction of dopamine and oxidant effect during cytarabine treatment could result in brain injury but could be prevented by oleic acid supplementation.

  13. Breast cancer leptomeningeal metastasis: the results of combined treatment and the comparison of methotrexate and liposomal cytarabine as intra-cerebrospinal fluid chemotherapy.

    PubMed

    Niwińska, Anna; Rudnicka, Halina; Murawska, Magdalena

    2015-02-01

    This was a prospective observational study to assess the results of the treatment of patients with breast cancer leptomeningeal metastasis (LM) and to compare the efficacy of methotrexate and liposomal cytarabine in patients treated intrathecally by lumbar puncture. In this prospective observational study, 149 consecutive patients with breast cancer and LM treated between the years 1999 and 2011 were assessed. Multimodality treatment methods were used: systemic therapy in 77 patients, radiotherapy in 92 patients, intrathecal methotrexate in 81 patients, and intrathecal liposomal cytarabine in 15 patients. The median survival of all patients was 4.2 months. The median survival of patients in whom systemic intravenous/oral treatment was used was 6 months, in those who did not have systemic treatment, the median survival was 2 months (P < .001). The median survival of patients treated with intrathecal methotrexate was 4.2 months; in patients treated with intrathecal liposomal cytarabine, the median survival was 4.6 months, and in patients who did not receive intrathecal treatment, the median survival was 3.7 months (P = .717). Median survival after whole-brain radiotherapy was 4.6 months and with no radiotherapy, it was 3.2 months (P = .028). Multivariate analysis revealed a Karnofsky performance status (KPS) of > 70. Systemic intravenous/oral treatment and bone as a site of metastasis were factors prolonging survival from LM. Among treatment methods, only systemic therapy prolonged survival in patients with LM. Neither radiotherapy nor lumbar intrathecal therapy influenced survival in those patients; however, both methods alleviated signs and symptoms of LM. No difference in survival was observed in patients treated intrathecally with methotrexate and those treated with liposomal cytarabine. Treatment with both drugs was comparable. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Daunorubicin and Cytarabine Liposome in Newly Diagnosed Therapy-Related Acute Myeloid Leukemia (AML) or AML With Myelodysplasia-Related Changes.

    PubMed

    Kim, Miryoung; Williams, Sherry

    2018-03-01

    To evaluate the efficacy and safety of daunorubicin and cytarabine liposome in older adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). A literature search of PubMed and MEDLINE (January 2017 to January 2018) was performed using the terms CPX-351, Vyxeos, daunorubicin and cytarabine liposome, and acute myeloid leukemia. Phase I, II, and III clinical trials evaluating the efficacy and safety of daunorubicin and cytarabine liposome were reviewed with a specific focus on its use in older patients with newly diagnosed AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. The phase II trial demonstrated that daunorubicin and cytarabine liposome improved response rates (RR), but there was no difference in event-free survival and overall survival in the overall patient population. However, clinical benefit was most pronounced in secondary AML with an increased RR and survival. The phase III trial illustrated that daunorubicin and cytarabine liposome improved survival and RR with tolerable toxicity compared with standard 7 plus 3 (daunorubicin and cytarabine) in patients 60 to 75 years of age with t-AML or AML-MRC. More patients proceeded to a stem cell transplant, and 30-day and 60-day mortality was lower with daunorubicin and cytarabine liposome. Grade 3 to 5 toxicities were similar between the 2 groups, except daunorubicin and cytarabine liposome had prolonged cytopenia and a higher risk of hemorrhage. Daunorubicin and cytarabine liposome improves RR and survival, with tolerable toxicity in older patients with t-AML or AML-MRC.

  15. Inhibition of histone deacetylases 1 and 6 enhances cytarabine-induced apoptosis in pediatric acute myeloid leukemia cells.

    PubMed

    Xu, Xuelian; Xie, Chengzhi; Edwards, Holly; Zhou, Hui; Buck, Steven A; Ge, Yubin

    2011-02-16

    Pediatric acute myeloid leukemia (AML) remains a challenging disease to treat even with intensified cytarabine-based chemotherapy. Histone deacetylases (HDACs) have been reported to be promising therapeutic targets for treating AML. However, HDAC family members that are involved in chemotherapy sensitivities remain unknown. In this study, we sought to identify members of the HDAC family that are involved in cytarabine sensitivities, and to select the optimal HDACI that is most efficacious when combined with cytarabine for treating children with AML. Expression profiles of classes I, II, and IV HDACs in 4 pediatric AML cell lines were determined by Western blotting. Inhibition of class I HDACs by different HDACIs was measured post immnunoprecipitation. Individual down-regulation of HDACs in pediatric AML cells was performed with lentiviral shRNA. The effects of cytarabine and HDACIs on apoptosis were determined by flow cytometry analysis. Treatments with structurally diverse HDACIs and HDAC shRNA knockdown experiments revealed that down-regulation of both HDACs 1 and 6 is critical in enhancing cytarabine-induced apoptosis in pediatric AML, at least partly mediated by Bim. However, down-regulation of HDAC2 may negatively impact cytarabine sensitivities in the disease. At clinically achievable concentrations, HDACIs that simultaneously inhibited both HDACs 1 and 6 showed the best anti-leukemic activities and significantly enhanced cytarabine-induced apoptosis. Our results further confirm that HDACs are bona fide therapeutic targets for treating pediatric AML and suggest that pan-HDACIs may be more beneficial than isoform-specific drugs.

  16. Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis.

    PubMed

    Jahn, Franziska; Jordan, Karin; Behlendorf, Timo; Globig, Cordula; Schmoll, Hans-Joachim; Müller-Tidow, Carsten; Jordan, Berit

    2015-01-01

    Although rare, neoplastic meningitis (NM) has been increasingly observed in patients with cancer due to the prolonged course of the disease. Intrathecal chemotherapy with methotrexate or cytarabine with repeating injection schedules of 2-3 times per week is currently the mainstay of treatment. An efficacious and comfortable treatment alternative might be represented by liposomal cytarabine. In this retrospective study, we reviewed all patients with NM due to solid tumors or hematological malignancies treated with liposomal cytarabine at our institution between March 2004 and September 2011. The primary endpoint was treatment response, which was defined as improvement in neurological symptoms and/or conversion of the initial cerebrospinal fluid cytology and/or response in the radiological findings. The main secondary endpoint was safety. Fifty-one adult patients were evaluable for safety and 44 patients for efficacy. In 36 patients (81.8%), a treatment response was achieved. The median overall survival after diagnosis of NM was 11 months (95% confidence interval 8.8-13.2). Adverse events grade 1-4 occurred in 31 patients (60.8%), whereas grade 3-4 occurred in 18 patients (35.3%). The encouraging efficacy and safety data obtained in our analysis and the convenient administration schedule make intrathecal liposomal cytarabine a favorable treatment option for NM patients.

  17. AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair.

    PubMed

    Ford, James B; Baturin, Dmitry; Burleson, Tamara M; Van Linden, Annemie A; Kim, Yong-Mi; Porter, Christopher C

    2015-09-29

    While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine and that mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.

  18. AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

    PubMed Central

    Burleson, Tamara M.; Van Linden, Annemie A.; Kim, Yong-Mi; Porter, Christopher C.

    2015-01-01

    While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine. Mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia. PMID:26334102

  19. Inhibition of Histone Deacetylases 1 and 6 Enhances Cytarabine-Induced Apoptosis in Pediatric Acute Myeloid Leukemia Cells

    PubMed Central

    Xu, Xuelian; Xie, Chengzhi; Edwards, Holly; Zhou, Hui; Buck, Steven A.; Ge, Yubin

    2011-01-01

    Background Pediatric acute myeloid leukemia (AML) remains a challenging disease to treat even with intensified cytarabine-based chemotherapy. Histone deacetylases (HDACs) have been reported to be promising therapeutic targets for treating AML. However, HDAC family members that are involved in chemotherapy sensitivities remain unknown. In this study, we sought to identify members of the HDAC family that are involved in cytarabine sensitivities, and to select the optimal HDACI that is most efficacious when combined with cytarabine for treating children with AML. Methodology Expression profiles of classes I, II, and IV HDACs in 4 pediatric AML cell lines were determined by Western blotting. Inhibition of class I HDACs by different HDACIs was measured post immnunoprecipitation. Individual down-regulation of HDACs in pediatric AML cells was performed with lentiviral shRNA. The effects of cytarabine and HDACIs on apoptosis were determined by flow cytometry analysis. Results Treatments with structurally diverse HDACIs and HDAC shRNA knockdown experiments revealed that down-regulation of both HDACs 1 and 6 is critical in enhancing cytarabine-induced apoptosis in pediatric AML, at least partly mediated by Bim. However, down-regulation of HDAC2 may negatively impact cytarabine sensitivities in the disease. At clinically achievable concentrations, HDACIs that simultaneously inhibited both HDACs 1 and 6 showed the best anti-leukemic activities and significantly enhanced cytarabine-induced apoptosis. Conclusion Our results further confirm that HDACs are bona fide therapeutic targets for treating pediatric AML and suggest that pan-HDACIs may be more beneficial than isoform-specific drugs. PMID:21359182

  20. Simultaneous determination of clofarabine and cytarabine in human plasma by LC-MS/MS.

    PubMed

    Büttner, Božena; Oertel, Reinhard; Schetelig, Johannes; Middeke, Jan Moritz; Bornhäuser, Martin; Seeling, Andreas; Knoth, Holger

    2016-06-05

    Combination of cytostatic agents is a basic principle in the treatment of cancer. For the treatment of acute myeloid leukemia (AML), purine analogs, like clofarabine and cytarabine act synergistically. Little is known, however, on their interaction in vivo. We developed a method for the simultaneous determination of clofarabine and cytarabine in human plasma. The substances were extracted from plasma samples by protein precipitation with acetonitrile. Cladribine was the internal standard (IS). The analytes were separated on Synergi HydroRP column (150mm×2.0mm, 4μm) and a triple-quadrupole mass spectrometry with an electrospray ionisation (ESI) source was applied for detection. The mobile phase consisted of acetonitrile, ammonium acetate 2mM and 0.5% formic acid in a gradient mode at a flow rate of 0.5ml/min. The injection volume was 10μl and the total run time was 6.0min. Retention times were 2.46min for clofarabine, 0.97min for cytarabine and 2.43min for the IS. Calibration ranges were 8-1000ng/ml for clofarabine and 20-2500ng/ml for cytarabine. The intra-day and inter-day precision was less than 15% and the relative standard deviation was all within ±15%. This new method allows a rapid and simple determination of both clofarabine and cytarabine in human plasma. It was applied to a pharmacokinetic investigation within a hematological trial in adult patients with AML. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia

    PubMed Central

    Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

    2017-01-01

    Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre-processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)-gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein-DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid-repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF-pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF-gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA-box binding protein associated factor 1 and CCCTC

  2. Bioinformatic analysis of the effects and mechanisms of decitabine and cytarabine on acute myeloid leukemia.

    PubMed

    Zhou, Shiyong; Liu, Pengfei; Zhang, Huilai

    2017-07-01

    Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre‑processing. Gene Ontology (GO) analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Analysis Discovery. Genes corresponding to the differentially methylated sites were obtained using the annotation package of the methylation microarray platform. The overlapping genes were identified, which exhibited the opposite variation trend between gene expression and DNA methylation. Important transcription factor (TF)‑gene pairs were screened out, and a regulated network subsequently constructed. A total of 190 DEGs and 540 differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine. A total of 36 GO terms of DEGs were enriched, including nucleosomes, protein‑DNA complexes and the nucleosome assembly. The 540 differentially methylated sites were located on 240 genes, including the acid‑repeat containing protein (ACRC) gene that was additionally differentially expressed. In addition, 60 TF pairs and overlapped methylated sites, and 140 TF‑pairs and DEGs were screened out. The regulated network included 68 nodes and 140 TF‑gene pairs. The present study identified various genes including ACRC and proliferating cell nuclear antigen, in addition to various TFs, including TATA‑box binding protein associated factor 1 and

  3. Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

    PubMed

    Gállego Pérez-Larraya, Jaime; Palma, José Alberto; Carmona-Iragui, María; Fernández-Torrón, Roberto; Irimia, Pablo; Rodríguez-Otero, Paula; Panizo, Carlos; Martínez-Vila, Eduardo

    2011-07-01

    Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

  4. Synthesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid bilayers and monolayers.

    PubMed

    Sarpietro, Maria Grazia; Ottimo, Sara; Giuffrida, Maria Chiara; Rocco, Flavio; Ceruti, Maurizio; Castelli, Francesco

    2011-03-15

    Cytarabine (1-β-D-arabinofuranosylcytosine, Ara-C), a pyrimidine nucleoside analogue, is an attractive therapeutic agent for the treatment of both acute and chronic myeloblastic leukemias. 1,1',2-tris-nor-Squalene acid (squaleneCOOH) has been conjugated to cytarabine with the formation of the squalenoyl-cytarabine prodrug, in order to improve the drug lipophilicity and, consequently, the affinity towards the environment of biological membranes, as well as of lipophilic carriers. The interaction of cytarabine and its prodrug with dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles and monolayers has been studied by the differential scanning calorimetry and the Langmuir-Blodgett techniques. The interaction has been evaluated considering the effect of the compounds on the DMPC MLV and monolayers behaviour. The aim was to have information on the interaction of the drug and the prodrug with the biological membranes and on the possibility to use liposomes as carriers for the prodrug. The results showed an improved affinity of the prodrug with MLV and monolayers with respect to the free drug. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Antiglioma effects of cytarabine on leptomeningeal metastasis of high-grade glioma by targeting the PI3K/Akt/mTOR pathway.

    PubMed

    Zhao, Kai-Hong; Zhang, Can; Bai, Yue; Li, Yan; Kang, Xun; Chen, Jian-Xin; Yao, Kun; Jiang, Tao; Zhong, Xiao-Song; Li, Wen-Bin

    2017-01-01

    Leptomeningeal metastasis (LM) of high-grade glioma is a highly lethal disease requiring new effective therapeutic measures. For both de novo or relapsed glioma with LM, intrathecal cytarabine chemotherapy is not frequently used for first-line and relapse protocols. We encountered a clinical case demonstrating effective application of cytarabine in high-grade glioma with LM, prompting us to explore the effects of cytarabine on malignant glioma and molecular mechanisms of such effects through in vivo and in vitro experiments. The U87 cell line was selected to represent human glioma for studies. Cell viability was measured by MTT assay, plate colony formation assay, and trypan-blue dye exclusion test. Apoptosis was assessed by flow cytometry. Protein expression levels were detected by Western blot assay and immunohistochemistry. mRNA expression was examined by quantitative real-time reverse transcription polymerase chain reaction. Cytarabine inhibited tumor growth during the in vivo experiment. The present study confirmed that cytarabine inhibits proliferation and promotes apoptosis of U87 cells, and molecular analysis of this effect showed that cytarabine significantly reduces expression of phosphatidylinositol 3-kinase/serine/threonine kinase also known as the protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway, Ki-67, BCL2, and 4-1BB, and upregulates Bax and cleaved caspase-3. Our findings indicated that intrathecal administration of cytarabine manifests potential in prophylaxis and treatment of malignant glioma with LM. Effective medications for high-grade glioma with LM should contain cytarabine.

  6. Antiglioma effects of cytarabine on leptomeningeal metastasis of high-grade glioma by targeting the PI3K/Akt/mTOR pathway

    PubMed Central

    Zhao, Kai-Hong; Zhang, Can; Bai, Yue; Li, Yan; Kang, Xun; Chen, Jian-Xin; Yao, Kun; Jiang, Tao; Zhong, Xiao-Song; Li, Wen-Bin

    2017-01-01

    Leptomeningeal metastasis (LM) of high-grade glioma is a highly lethal disease requiring new effective therapeutic measures. For both de novo or relapsed glioma with LM, intrathecal cytarabine chemotherapy is not frequently used for first-line and relapse protocols. We encountered a clinical case demonstrating effective application of cytarabine in high-grade glioma with LM, prompting us to explore the effects of cytarabine on malignant glioma and molecular mechanisms of such effects through in vivo and in vitro experiments. The U87 cell line was selected to represent human glioma for studies. Cell viability was measured by MTT assay, plate colony formation assay, and trypan-blue dye exclusion test. Apoptosis was assessed by flow cytometry. Protein expression levels were detected by Western blot assay and immunohistochemistry. mRNA expression was examined by quantitative real-time reverse transcription polymerase chain reaction. Cytarabine inhibited tumor growth during the in vivo experiment. The present study confirmed that cytarabine inhibits proliferation and promotes apoptosis of U87 cells, and molecular analysis of this effect showed that cytarabine significantly reduces expression of phosphatidylinositol 3-kinase/serine/threonine kinase also known as the protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway, Ki-67, BCL2, and 4-1BB, and upregulates Bax and cleaved caspase-3. Our findings indicated that intrathecal administration of cytarabine manifests potential in prophylaxis and treatment of malignant glioma with LM. Effective medications for high-grade glioma with LM should contain cytarabine. PMID:28721010

  7. Safety and tolerability of intrathecal liposomal cytarabine as central nervous system prophylaxis in patients with acute lymphoblastic leukemia.

    PubMed

    Valentin, Angelika; Troppan, Katharina; Pfeilstöcker, Michael; Nösslinger, Thomas; Linkesch, Werner; Neumeister, Peter

    2014-08-01

    Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in up to 15% of patients and is frequently associated with poor outcome. The purpose of our study was to evaluate the efficacy and safety of a slow-release liposomal formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal cytarabine on a compassionate use basis. After a median observation period of 23 months (range 2-118) only two patients experienced a combined medullary-leptomeningeal disease recurrence after primary diagnosis. Except for headache grade 2 in two patients, no specific toxicity attributable to IT liposomal cytarabine application was noted. Long-term neurological side effects were not observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears to be feasible and well tolerated.

  8. Improving antiproliferative effect of the anticancer drug cytarabine on human promyelocytic leukemia cells by coating on Fe3O4@SiO2 nanoparticles.

    PubMed

    Shahabadi, Nahid; Falsafi, Monireh; Mansouri, Kamran

    2016-05-01

    In this study, Fe3O4@SiO2-cytarabine magnetic nanoparticles (MNPs) were prepared via chemical coprecipitation reaction and coating silica on the surface of Fe3O4 MNPs by Stöber method via sol-gel process. The surface of Fe3O4@SiO2 MNPs was modified by an anticancer drug, cytarabine. The structural properties of the samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Zetasizer analyzer, and transmission electron microscopy (TEM). The results indicated that the crystalline phase of iron oxide NPs was magnetite (Fe3O4) and the average sizes of Fe3O4@SiO2-cytarabine MNPs were about 23 nm. Also, the surface characterization of Fe3O4@SiO2-cytarabine MNPs by FT-IR showed that successful coating of Fe3O4 NPs with SiO2 and binding of cytarabine drug onto the surface of Fe3O4@SiO2 MNPs were through the hydroxyl groups of the drug. The in vitro cytotoxic activity of Fe3O4@SiO2-cytarabine MNPs was investigated against cancer cell line (HL60) in comparison with cytarabine using MTT colorimetric assay. The obtained results showed that the effect of Fe3O4@SiO2-cytarabine magnetic nanoparticles on the cell lines were about two orders of magnitude higher than that of cytarabine. Furthermore, in vitro DNA binding studies were investigated by UV-vis, circular dichroism, and fluorescence spectroscopy. The results for DNA binding illustrated that DNA aggregated on Fe3O4@SiO2-cytarabine MNPs via groove binding. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Probing the binding reaction of cytarabine to human serum albumin using multispectroscopic techniques with the aid of molecular docking.

    PubMed

    Xu, Liang; Hu, Yan-Xi; Li, Jin; Liu, Yu-Feng; Zhang, Li; Ai, Hai-Xin; Liu, Hong-Sheng

    2017-08-01

    Cytarabine is a kind of chemotherapy medication. In the present study, the molecular interaction between cytarabine and human serum albumin (HSA) was investigated via fluorescence, UV-vis absorption, circular dichroism (CD) spectroscopy and molecular docking method under simulative physiological conditions. It was found that cytarabine could effectively quench the intrinsic fluorescence of HSA through a static quenching process. The apparent binding constants between drug and HSA at 288, 293 and 298K were estimated to be in the order of 10 3 L·mol -1 . The thermodynamic parameters ΔH°, ΔG°and ΔS° were calculated, in which the negative ΔG°suggested that the binding of cytarabine to HSA was spontaneous, moreover the negative ΔS°and negative ΔH°revealed that van der Waals force and hydrogen bonds were the major forces to stabilize the protein-cytarabine (1:1) complex. The competitive binding experiments showed that the primary binding site of cytarabine was located in the site I (subdomain IIA) of HSA. In addition, the binding distance was calculated to be 3.4nm according to the Förster no-radiation energy transfer theory. The analysis of CD and three-dimensional (3D) fluorescence spectra demonstrated that the binding of drug to HSA induced some conformational changes in HSA. The molecular docking study also led to the same conclusion obtained from the spectral results. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Lipid based noninvasive vesicular formulation of cytarabine: Nanodeformable liposomes.

    PubMed

    Raj, Rakesh; Raj, Pooja Mongia; Ram, Alpana

    2016-06-10

    Leukemia is the common cause of death and worldwide incidence of this disease is increasing. Chemotherapy is the first choice for leukemia treatment, but the major limitations of standard therapy are its side effects and poor patient compliances. Therefore it is imperative to look for a therapeutic system with lesser side effects urgently to address the underlying causes of poor treatment outcomes. In such a scenario transdermal route for delivery of chemotherapeutic drugs could be a better alternative to provide sustained drug level, enhanced activity, self administration and better patient compliances. The present work is focus on the design of nanolipid based transdermal carrier, deformable liposomes bearing cytarabine as a model drug for effective delivery of drug with enhanced transdermal flux. Developed nanocarriers were characterized for their size, morphology, entrapment efficiency, skin penetration and irritation. It could be concluded that nanodeformable liposomes accentuated transdermal flux of cytarabine and could provide a new strategy for leukemia. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Cytarabine: cytocidal effect on normal and leukemic lymphocytes. Synergism with x-rays and comparison with mechlorethamine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schrek, R.; Stefani, S.S.

    To study the in vitro toxicity of cytarabine to nondividing lymphocytes from normal persons and from patients with chronic lymphocytic leukemia, the cells were incubated with the drug at 37/sup 0/C for 3 to 7 days and the number of viable lymphocytes was counted before and after incubation. Cytarabine produced a cytocidal effect on normal and leukemic lymphocytes, and the leukemic lymphocytes were more sensitive than the normal cells. Both deoxycytidine and incubation at 27/sup 0/C protected the cells from the cytotoxicity of the drug. The combination of cytarabine and x-irradiation produced a synergistic cytocidal effect of normal lymphocytes. Inmore » contrast, mechlorethamine was usually less toxic to leukemic than to normal lymphocytes and produced an additive, not a synergistic effect with x-irradiation.« less

  12. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia.

    PubMed

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-06-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m(2) in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3-4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). Copyright© Ferrata Storti Foundation.

  13. Fludarabine and cytarabine versus high-dose cytarabine in consolidation treatment of t(8; 21) acute myeloid leukemia: A prospective, randomized study.

    PubMed

    Li, Ruiqi; Hu, Xiaoxia; Wang, Libing; Cheng, Hui; Lv, Shuqing; Zhang, Weiping; Wang, Jianmin; Yang, Jianmin; Song, Xianmin

    2017-01-01

    Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30-40% patients, with only 50-60% of patients with t(8;21) AML cured with regimens containing high-dose cytarabine (HD-Ara-C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD-Ara-C (n = 22). Our study showed that at 36-months, relapse-free survival (RFS) was 81.73% in the FA arm and 50.73% in the HD-Ara-C arm (P = 0.04), overall survival (OS) was 91.1% and 48.4% (P = 0.01) in the FA arm and in the HD-Ara-C arm respectively; whereas cumulative incidence of relapse (CIR) was 18.27% and 47.39%, in the FA arm and in the HD-Ara-C arm respectively (P = 0.05). In our study, treatment with FA, MRD2 status (reduction ≥ 3-log) and absence of c-kit mutations were identified as independent prognostic factors for lower risk of relapse, improved RFS and OS. We also found RFS for patients without c-kit mutations was 100% in FA arm, and 57.8% in HD-Ara-C arm at 36 months (P = 0.005); OS of both groups at 36 months was 100% and 51.4%, respectively (P = 0.004), suggesting a benefit of consolidation therapy with FA for t(8;21) AML patients, especially, those without c-kit mutations (Clinicaltrials.org ID NCT# 02024308). Am. J. Hematol. 92:12-17, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Combination screening in vitro identifies synergistically acting KP372-1 and cytarabine against acute myeloid leukemia.

    PubMed

    Österroos, A; Kashif, M; Haglund, C; Blom, K; Höglund, M; Andersson, C; Gustafsson, M G; Eriksson, A; Larsson, R

    2016-10-15

    Cytogenetic lesions often alter kinase signaling in acute myeloid leukemia (AML) and the addition of kinase inhibitors to the treatment arsenal is of interest. We have screened a kinase inhibitor library and performed combination testing to find promising drug-combinations for synergistic killing of AML cells. Cytotoxicity of 160 compounds in the library InhibitorSelect™ 384-Well Protein Kinase Inhibitor I was measured using the fluorometric microculture cytotoxicity assay (FMCA) in three AML cell lines. The 15 most potent substances were evaluated for dose-response. The 6 most cytotoxic compounds underwent combination synergy analysis based on the FMCA readouts after either simultaneous or sequential drug addition in AML cell lines. The 4 combinations showing the highest level of synergy were evaluated in 5 primary AML samples. Synergistic calculations were performed using the combination interaction analysis package COMBIA, written in R, using the Bliss independence model. Based on obtained results, an iterative combination search was performed using the therapeutic algorithmic combinatorial screen (TACS) algorithm. Of 160 substances, cell survival was ⩽50% at <0.5μM for Cdk/Crk inhibitor, KP372-1, synthetic fascaplysin, herbimycin A, PDGF receptor tyrosine kinase inhibitor IV and reference-drug cytarabine. KP372-1, synthetic fascaplysin or herbimycin A obtained synergy when combined with cytarabine in AML cell lines MV4-11 and HL-60. KP372-1 added 24h before cytarabine gave similar results in patient cells. The iterative search gave further improved synergy between cytarabine and KP372-1. In conclusion, our in vitro studies suggest that combining KP372-1 and cytarabine is a potent and synergistic drug combination in AML. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. MK-2206 induces apoptosis of AML cells and enhances the cytotoxicity of cytarabine.

    PubMed

    Lu, Jeng-Wei; Lin, Yu-Min; Lai, Yen-Ling; Chen, Chien-Yuan; Hu, Chung-Yi; Tien, Hwei-Fang; Ou, Da-Liang; Lin, Liang-In

    2015-07-01

    Genetic alterations in the PI3K/AKT cascade have been linked to various human cancers including acute myeloid leukemia (AML) and have emerged to be promising targets for treatment. In this study, we explored the molecular mechanism and clinical implication of a specific allosteric AKT inhibitor, MK-2206, in the treatment of AML. Four leukemia cell lines, MV-4-11, MOLM-13, OCI/AML3, and U937, were used. Apoptosis and cell cycle distribution were determined by flow cytometry analysis. Expression of anti-apoptotic protein family and glycogen synthase kinase 3β (GSK3β) signaling was determined by western blotting. Drug combination effects of MK-2206 with cytarabine were evaluated by cell proliferation assay, and the combination index values were calculated by CompuSyn software. MK-2206 had no effect on normal peripheral blood mononuclear cells, but induced G1-phase arrest and apoptosis in leukemia cells. Among anti-apoptotic Bcl-2 family members, only myeloid cell leukemia-1 (Mcl-1) was significantly suppressed. Mcl-1 suppression by MK-2206 was closely associated with decreased GSK3β phosphorylation at Ser9, an event leads to GSK3β activation. Furthermore, the effect of MK-2206 on Mcl-1 downregulation was abolished by GSK3β inhibitor, lithium chloride and proteasome inhibitor, MG-132, suggesting that MK-2206 acted through a GSK3β-mediated, proteasome-dependent protein degradation. In addition, co-administration of MK-2206 with cytarabine could enhance the cytotoxic efficacy of cytarabine in leukemia cell lines. In conclusion, we have demonstrated that MK-2206 is an active agent in AML and its efficacy as in combination with cytarabine is implicated.

  16. DNA-binding study of anticancer drug cytarabine by spectroscopic and molecular docking techniques.

    PubMed

    Shahabadi, Nahid; Falsafi, Monireh; Maghsudi, Maryam

    2017-01-02

    The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 10 4 L mol -1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure -20.61 KJ mol -1 . This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.

  17. Retrospective Comparison of Fludarabine in Combination With Intermediate-Dose Cytarabine Versus High-Dose Cytarabine As Consolidation Therapies for Acute Myeloid Leukemia

    PubMed Central

    Zhang, Wenjun; Ding, Yi; Wu, Hao; Chen, Yuhua; Lu, Huina; Chen, Chunying; Fu, Jianfei; Wang, Weiguang; Liang, Aibin; Zou, Shanhua

    2014-01-01

    Abstract This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission. Disease-free survival (DFS) and overall survival (OS) based on age (≥60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013. Total 82 patients (FA, n = 45; HiDAC, n = 37; 14–65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients. PMID:25501050

  18. Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients

    PubMed Central

    Gamazon, Eric R.; Lamba, Jatinder K.; Pounds, Stanley; Stark, Amy L.; Wheeler, Heather E.; Cao, Xueyuan; Im, Hae K.; Mitra, Amit K.; Rubnitz, Jeffrey E.; Ribeiro, Raul C.; Raimondi, Susana; Campana, Dario; Crews, Kristine R.; Wong, Shan S.; Welsh, Marleen; Hulur, Imge; Gorsic, Lidija; Hartford, Christine M.; Zhang, Wei; Cox, Nancy J.; Dolan, M. Eileen

    2013-01-01

    A whole-genome approach was used to investigate the genetic determinants of cytarabine-induced cytotoxicity. We performed a meta-analysis of genome-wide association studies involving 523 lymphoblastoid cell lines (LCLs) from individuals of European, African, Asian, and African American ancestry. Several of the highest-ranked single-nucleotide polymorphisms (SNPs) were within the mutated in colorectal cancers (MCC) gene. MCC expression was induced by cytarabine treatment from 1.7- to 26.6-fold in LCLs. A total of 33 SNPs ranked at the top of the meta-analysis (P < 10−5) were successfully tested in a clinical trial of patients randomized to receive low-dose or high-dose cytarabine plus daunorubicin and etoposide; of these, 18 showed association (P < .05) with either cytarabine 50% inhibitory concentration in leukemia cells or clinical response parameters (minimal residual disease, overall survival (OS), and treatment-related mortality). This count (n = 18) was significantly greater than expected by chance (P = .016). For rs1203633, LCLs with AA genotype were more sensitive to cytarabine-induced cytotoxicity (P = 1.31 × 10−6) and AA (vs GA or GG) genotype was associated with poorer OS (P = .015), likely as a result of greater treatment-related mortality (P = .0037) in patients with acute myeloid leukemia (AML). This multicenter AML02 study trial was registered at www.clinicaltrials.gov as #NCT00136084. PMID:23538338

  19. Venetoclax and low-dose cytarabine induced complete remission in a patient with high-risk acute myeloid leukemia: a case report.

    PubMed

    Liu, Bingshan; Narurkar, Roshni; Hanmantgad, Madhura; Zafar, Wahib; Song, Yongping; Liu, Delong

    2018-05-21

    Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.

  20. Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage.

    PubMed

    Xie, Chengzhi; Edwards, Holly; Caldwell, J Timothy; Wang, Guan; Taub, Jeffrey W; Ge, Yubin

    2015-02-01

    Resistance to cytarabine and anthracycline-based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl-2, Bcl-xL, and/or Mcl-1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti-apoptotic Bcl-2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan-Bcl-2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double-strand breaks (DSBs) preceded a decrease of Mcl-1 levels, nuclear translocation of Bcl-2, Bcl-xL, and Mcl-1, and apoptosis. These results indicate that obatoclax enhances cytarabine-induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA-damaging agents in AML and possibly a broader range of malignancies. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Double labeling of human leukemic cells using /sup 3/H-cytarabine and monoclonal antibody against bromodeoxyuridine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Raza, A.; Preisler, H.D.

    A new technique using immunofluorescence and autoradiography is described, in which the DNA of cells in S phase are labeled with two different probes. This method makes it possible to study the relationship between DNA synthesis and the uptake and/or incorporation of chemotherapeutic agents into normal or neoplastic cells. An example is provided in which the incorporation of /sup 3/H-cytarabine into DNA is demonstrated to occur only in cells which were synthesizing DNA during exposure to /sup 3/H-cytarabine. Other radioactively labeled probes can be used as well.

  2. Suspected drug-induced infiltrative lung disease culminating in acute respiratory failure in a dog treated with cytarabine and prednisone.

    PubMed

    Hart, Samantha K; Waddell, Lori

    2016-11-01

    To describe a case of suspected drug-induced infiltrative lung disease (ILD) and acute respiratory failure associated with the administration of cytarabine and prednisone in a dog requiring mechanical ventilation. A 4.5-year-old, female spayed Yorkshire Terrier presented to the ICU with acute onset of respiratory distress following a 24-hour cytarabine infusion. The patient was previously diagnosed with meningoencephalitis of unknown etiology (MUO), caudal occipital malformation, and syringohydromyelia, and was being treated with oral prednisone and levetiracetam, and cytarabine infusions. The patient developed tachypnea and dyspnea, and had diffuse crackles on auscultation of all lung fields, and hypoxemia 6 hours following completion of the fourth cytarabine infusion (300 mg/m 2 ). Thoracic radiographs revealed diffuse, bilateral infiltrates consistent with noncardiogenic pulmonary edema or acute respiratory distress syndrome. Respiratory distress and hypoxemia persisted despite oxygen supplementation and furosemide therapy and led to initiation of mechanical ventilation. Approximately 12 hours later, the dog became progressively hypoxemic with worsening pulmonary edema. The owners elected euthanasia. Postmortem examination revealed pulmonary edema and diffuse interstitial pneumonia. Histopathologic evaluation revealed pulmonary edema, severe acute neutrophilic and histiocytic pneumonia, and multifocal interstitial fibrosis. Bacterial culture yielded no growth. Drug-induced ILD is rarely reported in the veterinary literature, and has not previously been reported in dogs receiving cytarabine. As with administration of any medication, adverse events may occur. While ILD is unlikely to be commonly recognized, it may be considered in veterinary patients receiving chemotherapy that acutely become dyspneic. © Veterinary Emergency and Critical Care Society 2016.

  3. Methotrexate and Cytarabine-Loaded Nanocarriers for Multidrug Cancer Therapy. Spectroscopic Study.

    PubMed

    Pentak, Danuta; Kozik, Violetta; Bąk, Andrzej; Dybał, Paulina; Sochanik, Aleksander; Jampilek, Josef

    2016-12-08

    Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC) interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance 2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR) were consistent with the results obtained by Differential Scanning Calorimetry (DSC). Transmission Electron Microscopy (TEM) was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR).

  4. Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

    PubMed

    González-Barca, E; Canales, M; Salar, A; Ferreiro-Martínez, J J; Ferrer-Bordes, S; García-Marco, J A; Sánchez-Blanco, J J; García-Frade, J; Peñalver, J; Bello-López, J L; Sancho, J M; Caballero, D

    2016-05-01

    The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL.

  5. Successful use of high-dose cytarabine in a patient with acute myeloid leukemia and severe hepatic dysfunction.

    PubMed

    Barker, Jacob A; Marini, Bernard L; Bixby, Dale; Perissinotti, Anthony J

    2016-12-01

    Acute myeloid leukemia is a hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and other tissues. Prognosis is poor with 5-year survival rates ranging from 5-65% depending on demographic and clinical features. Outcomes are worse for patients that have an antecedent myeloproliferative neoplasm that evolves to acute myeloid leukemia, with a survival rate of <10%. Treatment for acute myeloid leukemia has remained cytarabine and an anthracycline given in the standard 3 + 7 regimen. However, for patients with liver dysfunction this regimen, among many others, cannot be given safely. There is currently a lack of data regarding the use of cytarabine in patients with severe hepatic dysfunction. In this case report, we present a patient with secondary acute myeloid leukemia who successfully received a modified regimen of high-dose cytarabine while in severe hepatic dysfunction (bilirubin >15 mg/dL). © The Author(s) 2015.

  6. Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology.

    PubMed

    Early, P J; Crook, K I; Williams, L M; Davis, E G; Muñana, K R; Papich, M G; Messenger, K M

    2017-08-01

    The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25 mg/m 2 /h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (C MAX ) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma. © 2016 John Wiley & Sons Ltd.

  7. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial.

    PubMed

    Willemze, Roelof; Suciu, Stefan; Meloni, Giovanna; Labar, Boris; Marie, Jean-Pierre; Halkes, Constantijn J M; Muus, Petra; Mistrik, Martin; Amadori, Sergio; Specchia, Giorgina; Fabbiano, Francesco; Nobile, Francesco; Sborgia, Marco; Camera, Andrea; Selleslag, Dominik L D; Lefrère, Francois; Magro, Domenico; Sica, Simona; Cantore, Nicola; Beksac, Meral; Berneman, Zwi; Thomas, Xavier; Melillo, Lorella; Guimaraes, Jose E; Leoni, Pietro; Luppi, Mario; Mitra, Maria E; Bron, Dominique; Fillet, Georges; Marijt, Erik W A; Venditti, Adriano; Hagemeijer, Anne; Mancini, Marco; Jansen, Joop; Cilloni, Daniela; Meert, Liv; Fazi, Paola; Vignetti, Marco; Trisolini, Silvia M; Mandelli, Franco; de Witte, Theo

    2014-01-20

    Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD

  8. Aptamer Internalization via Endocytosis Inducing S-Phase Arrest and Priming Maver-1 Lymphoma Cells for Cytarabine Chemotherapy.

    PubMed

    Li, Huan; Yang, Shuanghui; Yu, Ge; Shen, Liangfang; Fan, Jia; Xu, Ling; Zhang, Hedong; Zhao, Nianxi; Zeng, Zihua; Hu, Tony; Wen, Jianguo; Zu, Youli

    2017-01-01

    The goal of precision therapy is to efficiently treat cancer without side effects. Aptamers are a class of small ligands composed of single-stranded oligonucleotides that bind to their targets with high affinity and specificity. In this study, we identified an ssDNA aptamer specifically targeting Maver-1 lymphoma cells with high binding affinity (K d = 70±8 pmol/L). Interestingly, cellular cycle studies revealed that exposure of Maver-1 cells to synthetic aptamers triggered S-phase arrest of 40% of the cells (vs. 18% baseline). Confocal microscopy confirmed specific cell binding of aptamers and the resultant endocytosis into Maver-1 cells. Subsequent functional assays validated the fact that aptamer internalization into targeted cells is a prerequisite for Maver-1 cell growth inhibition. Importantly, aptamer-induced S-phase arrest induced enhanced chemotherapeutic results involving cytarabine, which primarily kills lymphoma cells at S-phase. Combination treatments revealed that aptamer re-exposure considerably primed Maver-1 cells for cytarabine chemotherapy, thus achieving a synergistic killing effect by reaching cell death rates as high as 61% (vs. 13% or 14% induced by aptamer or cytarabine treatment alone). These findings demonstrated that aptamers do not only act as molecular ligands but can also function as biotherapeutic agents by inducing S-phase arrest of lymphoma cells. In addition, logical combination of aptamer and cytarabine treatments ushers the way to a unique approach in precision lymphoma chemotherapy.

  9. Aptamer Internalization via Endocytosis Inducing S-Phase Arrest and Priming Maver-1 Lymphoma Cells for Cytarabine Chemotherapy

    PubMed Central

    Li, Huan; Yang, Shuanghui; Yu, Ge; Shen, Liangfang; Fan, Jia; Xu, Ling; Zhang, Hedong; Zhao, Nianxi; Zeng, Zihua; Hu, Tony; Wen, Jianguo; Zu, Youli

    2017-01-01

    The goal of precision therapy is to efficiently treat cancer without side effects. Aptamers are a class of small ligands composed of single-stranded oligonucleotides that bind to their targets with high affinity and specificity. In this study, we identified an ssDNA aptamer specifically targeting Maver-1 lymphoma cells with high binding affinity (Kd = 70±8 pmol/L). Interestingly, cellular cycle studies revealed that exposure of Maver-1 cells to synthetic aptamers triggered S-phase arrest of 40% of the cells (vs. 18% baseline). Confocal microscopy confirmed specific cell binding of aptamers and the resultant endocytosis into Maver-1 cells. Subsequent functional assays validated the fact that aptamer internalization into targeted cells is a prerequisite for Maver-1 cell growth inhibition. Importantly, aptamer-induced S-phase arrest induced enhanced chemotherapeutic results involving cytarabine, which primarily kills lymphoma cells at S-phase. Combination treatments revealed that aptamer re-exposure considerably primed Maver-1 cells for cytarabine chemotherapy, thus achieving a synergistic killing effect by reaching cell death rates as high as 61% (vs. 13% or 14% induced by aptamer or cytarabine treatment alone). These findings demonstrated that aptamers do not only act as molecular ligands but can also function as biotherapeutic agents by inducing S-phase arrest of lymphoma cells. In addition, logical combination of aptamer and cytarabine treatments ushers the way to a unique approach in precision lymphoma chemotherapy. PMID:28435459

  10. Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

    PubMed

    Pugliese, Novella; Salvatore, Paola; Iula, Dora Vita; Catania, Maria Rosaria; Chiurazzi, Federico; Della Pepa, Roberta; Cerchione, Claudio; Raimondo, Marta; Giordano, Claudia; Simeone, Luigia; Caruso, Simona; Pane, Fabrizio; Picardi, Marco

    2017-07-01

    Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m 2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic

  11. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study

    PubMed Central

    Ravandi, Farhad; Ritchie, Ellen K.; Sayar, Hamid; Lancet, Jeffrey E.; Craig, Michael D.; Vey, Norbert; Strickland, Stephen A.; Schiller, Gary J.; Jabbour, Elias; Erba, Harry P.; Pigneux, Arnaud; Horst, Heinz-August; Recher, Christian; Klimek, Virginia M.; Cortes, Jorge; Roboz, Gail J.; Odenike, Olatoyosi; Thomas, Xavier; Havelange, Violaine; Maertens, Johan; Derigs, Hans-Günter; Heuser, Michael; Damon, Lloyd; Powell, Bayard L.; Gaidano, Gianluca; Carella, Angelo-Michele; Wei, Andrew; Hogge, Donna; Craig, Adam R.; Fox, Judith A.; Ward, Renee; Smith, Jennifer A.; Acton, Gary; Mehta, Cyrus; Stuart, Robert K.; Kantarjian, Hagop M.

    2016-01-01

    Summary Background Safe and effective treatments are urgently needed for patients with relapsed/refractory acute myeloid leukaemia (AML). We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed/refractory AML. Methods VALOR was a phase 3, double-blind, placebo-controlled trial conducted at 101 international sites. Patients were randomised 1:1 to vosaroxin (90 mg/m2 IV days 1,4) plus cytarabine (1 g/m2 IV days 1–5) (vos/cyt) or placebo plus cytarabine (pla/cyt) using a permuted block procedure stratified by disease status, age, and geographic location. All participants were blind to treatment assignment. Primary endpoints were overall survival (OS) and 30- and 60-day mortality. Efficacy analyses were by intention-to-treat; safety analyses included all treated patients. This study is registered at clinicaltrials.gov (NCT01191801). Findings Between December 2010 and September 2013, 711 patients were randomised to vos/cyt (n=356) or pla/cyt (n=355). Median OS was 7·5 months with vos/cyt and 6·1 months with pla/cyt (hazard ratio 0·87; unstratified log-rank p=0·061; stratified p=0·0241) and was supported by a sensitivity analysis censoring for subsequent transplant (6·7 and 5·3 months; p=0·0243). Complete remission (CR) rate was higher with vos/cyt vs pla/cyt (30·1% vs 16·3%, p<0·0001). Early mortality rates were equivalent (vos/cyt vs pla/cyt: 30-day, 7·9% vs 6·6%; 60-day, 19·7% vs 19·4%). Treatment-related deaths occurred at any time in 18 patients (5·1%) with vos/cyt and 8 (2·3%) with pla/cyt. Grade ≥3 adverse events more frequent with vos/cyt included febrile neutropenia (167/355 [47%] vs 117/350 [33%]), stomatitis (54 [15%] vs 10 [3%]), hypokalaemia (52 [15%] vs 21 [6%]), sepsis (42 [12%] vs 18 [5%]), and pneumonia (39 [11%] vs 26 [7%]). Interpretation Addition of vosaroxin to cytarabine prolonged survival in patients with relapsed/refractory AML

  12. The novel HSP90 inhibitor NVP-AUY922 shows synergistic anti-leukemic activity with cytarabine in vivo.

    PubMed

    Wendel, Torunn; Zhen, Yan; Suo, Zenhe; Bruheim, Skjalg; Wiedlocha, Antoni

    2016-01-15

    HSP90 is a molecular chaperone essential for stability, activity and intracellular sorting of many proteins, including oncoproteins, such as tyrosine kinases, transcription factors and cell cycle regulatory proteins. Therefore, inhibitors of HSP90 are being investigated for their potential as anti-cancer drugs. Here we show that the HSP90 inhibitor NVP-AUY922 induced degradation of the fusion oncoprotein FOP2-FGFR1 in a human acute myeloid leukemia (AML) cell line, KG-1a. Concordantly, downstream signaling cascades, such as STAT1, STAT3 and PLCγ were abrogated. At concentrations that caused FOP2-FGFR1 degradation and signaling abrogation, NVP-AUY922 treatment caused significant cell death and inhibition of proliferation of KG-1a cells in vitro. In an animal model for AML, NVP-AUY922 administrated alone showed no anti-leukemic activity. However, when NVP-AUY922 was administered in combination with cytarabine, the two compounds showed significant synergistic anti-leukemic activity in vivo. Thus NVP-AUY922 and cytarabine combination therapy might be a prospective strategy for AML treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study.

    PubMed

    Halpern, A B; Othus, M; Huebner, E M; Buckley, S A; Pogosova-Agadjanyan, E L; Orlowski, K F; Scott, B L; Becker, P S; Hendrie, P C; Chen, T L; Percival, M-E M; Estey, E H; Stirewalt, D L; Walter, R B

    2017-12-01

    DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC (granulocyte colony-stimulating factor (G-CSF); clofarabine; cytarabine) and G-CLAM (G-CSF; cladribine; cytarabine; mitoxantrone)). Thus, while meeting the prespecified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.

  14. Cytarabine and daunorubicin for the treatment of acute myeloid leukemia.

    PubMed

    Murphy, Tracy; Yee, Karen W L

    2017-11-01

    Acute myeloid leukemia (AML) is the most common acute forms of leukemia in adults. It has a poor long-term survival with a high relapse rate and at relapse, is commonly resistant to available therapies. The current combination of daunorubicin (DNR) for three days and cytarabine (Ara-C) as a continuous infusion for seven days, more commonly known as '3 + 7' has remained essentially unaltered over the last forty-four years and remains the standard induction regimen internationally. Areas covered: This paper will briefly review clinically important trials related to '3 + 7'. Somatic mutations in AML that are linked to chemoresistance to '3 + 7'will be discussed. Other topics covered include the novel ratiometric agent containing daunorubicin and cytarabine, CPX-351, and midostaurin in FLT3 mutated AML. Expert opinion: '3 + 7' continues to be the backbone of therapy for AML. However, genetic risk stratification should be used to determine patients who are unlikely to respond to standard intensive chemotherapy and hence, should be enrolled onto a clinical trial upfront. This will facilitate development of newer effective treatment strategies in AML. Patients with mutations that are associated with chemoresistance should be offered therapies which may circumvent or overcome these pathways.

  15. Autophagy is an important event for low-dose cytarabine treatment in acute myeloid leukemia cells.

    PubMed

    Chen, Liyun; Guo, Pei; Zhang, Yunxiang; Li, Xiaoyang; Jia, Peimin; Tong, Jianhua; Li, Junmin

    2017-09-01

    Cytarabine (Ara-c) has been an important agent in acute myeloid leukemia (AML) treatment for more than 40 years. While, the mechanisms underlying low dose cytarabine (LD Ara-c) is poorly understood. In this study, we investigated the therapeutic effect of LD Ara-C in vitro. U937 and HEL cell lines were treated with increasing dose of Ara-C and showed growth inhibition rates in a time and dose-dependent manner. Treatment with LD Ara-C (50nM) induced a time-dependent increase in expression of microtubule-associated protein light chain 3 (LC3) and beclin1, but degradation of sequestosome1 (p62) in both U937 and HEL cells. Characteristic of autophagosomes appeared after 24h treatment. Meanwhile, deregulation of Akt-mTOR pathway was also detected. When cultured in presence of autophagy inhibitors, autophagy and differentiation was reversed, and cell growth inhibition was also attenuated. Similar phenomenon could also be seen when beclin1 expression was down-regulated. Taken together, we concluded that LD Ara-C can induce autophagy in AML cells and appeared to play an important role in differentiation and death. Down-regulation of Akt-mTOR pathway is involved in these processes. We suggest that cytarabine-induced autophagy is not a pro-survival mechanism, but accounts for its antineoplastic effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia.

    PubMed

    Shah, Krupa; Mirza, Sheefa; Desai, Urja; Jain, Nayan; Rawal, Rakesh

    2016-01-01

    The aim of the study was to find a role of Curcumin from natural source to overcome drug resistance as well as to reduce cytotoxicity profile of the drug in Acute Myeloid Leukemia patients. Primary leukemic cells were obtained from AML patient's bone marrow. These cells were then exposed to different concentration of cytarabine and curcumin to find out IC50 values and also its effect on MDR genes like MDR1, BCRP, LRP and FLT3 by RT-PCR method. Our results suggested that curcumin down regulates MDR genes. Gene expression was decreased by 35.75, 31.30, 27.97 % for MDR1, LRP, BCRP respectively. In FLT3, it was 65.86 % for wild type and 31.79 % for FLT3-ITD. In addition to this, curcumin has also shown anti-proliferative effect as well as synergistic effect in combination with Cytarabine on primary leukemic cells. Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC50 value decreases when treated in combination.

  17. Identification of predictive markers of cytarabine response in AML by integrative analysis of gene-expression profiles with multiple phenotypes

    PubMed Central

    Lamba, Jatinder K; Crews, Kristine R; Pounds, Stanley B; Cao, Xueyuan; Gandhi, Varsha; Plunkett, William; Razzouk, Bassem I; Lamba, Vishal; Baker, Sharyn D; Raimondi, Susana C; Campana, Dario; Pui, Ching-Hon; Downing, James R; Rubnitz, Jeffrey E; Ribeiro, Raul C

    2011-01-01

    Aim To identify gene-expression signatures predicting cytarabine response by an integrative analysis of multiple clinical and pharmacological end points in acute myeloid leukemia (AML) patients. Materials & methods We performed an integrated analysis to associate the gene expression of diagnostic bone marrow blasts from acute myeloid leukemia (AML) patients treated in the discovery set (AML97; n = 42) and in the independent validation set (AML02; n = 46) with multiple clinical and pharmacological end points. Based on prior biological knowledge, we defined a gene to show a therapeutically beneficial (detrimental) pattern of association of its expression positively (negatively) correlated with favorable phenotypes such as intracellular cytarabine 5´-triphosphate levels, morphological response and event-free survival, and negatively (positively) correlated with unfavorable end points such as post-cytarabine DNA synthesis levels, minimal residual disease and cytarabine LC50. Results We identified 240 probe sets predicting a therapeutically beneficial pattern and 97 predicting detrimental pattern (p ≤ 0.005) in the discovery set. Of these, 60 were confirmed in the independent validation set. The validated probe sets correspond to genes involved in PIK3/PTEN/AKT/mTOR signaling, G-protein-coupled receptor signaling and leukemogenesis. This suggests that targeting these pathways as potential pharmacogenomic and therapeutic candidates could be useful for improving treatment outcomes in AML. Conclusion This study illustrates the power of integrated data analysis of genomic data as well as multiple clinical and pharmacologic end points in the identification of genes and pathways of biological relevance. PMID:21449673

  18. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.

    PubMed

    Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Schoch, Claudia; Fonatsch, Christa; Löffler, Helmut; Haferlach, Torsten; Ludwig, Wolf-Dieter; Maschmeyer, Georg; Staib, Peter; Aul, Carlo; Gruneisen, Andreas; Lengfelder, Eva; Frickhofen, Norbert; Kern, Wolfgang; Serve, Hubert L; Mesters, Rolf M; Sauerland, Maria Cristina; Heinecke, Achim

    2003-12-15

    To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age < 60 years] or 1 g/m2 [age > or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age < 60 years) or 0.5 g/m2 (age > or = 60 years) x 8 instead of maintenance. A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026). We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

  19. Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients.

    PubMed

    Kim, Inho; Koh, Youngil; Yoon, Sung-Soo; Park, Seonyang; Kim, Byoung Kook; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Cheong, June-Won; Lee, Hong-Kee; Kim, Sung-Hyun; Kim, Hyuk; Joo, Young Don; Lee, Sang-Min; Won, Jong-Ho; Park, Sung-Kyu; Hong, Dae-Sik; Kim, Se-Hyung; Sohn, Sang Kyun; Kim, Chul-Soo; Park, Eunkyung; Kim, Min Kyoung; Park, Moo Rim; Lee, Je-Hwan; Min, Yoo Hong

    2013-01-01

    We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Copyright © 2012 Wiley Periodicals, Inc.

  20. [A Case of a Multidisciplinary Team Approach to Serious Hand-Foot Syndrome Induced by High-Dose Cytarabine Therapy].

    PubMed

    Sakurada, Hiroaki; Aoi, Miki; Yuge, Masaaki; Sugimura, Yuriko; Kitamura, Kunio; Yamamura, Masumi; Tachi, Tomoya; Teramachi, Hitomi

    2016-07-01

    A 40's year-old female patient with acute myeloblastic leukemia received high-dose cytarabine(HD-Ara-C)as her third induction therapy. Because the pharmacist in charge noticed on a prior interview that she had experienced a mild skin eruption similar to hand-foot syndrome(HFS)in the previous round oftherapy(idarubicin and cytarabine), heparinoid lotion and hypoallergenic soap were used to prevent HFS. However, HFS occurred on day 3, and further developed on day 6 to grade 3 with painful erythema, swelling, and paresthesia affecting the entire surface of both hands. We cared for her with moisturization, lifestyle guidance, rotation of steroid ointment, and occlusive dressing techniques according to a multidisciplinary team approach composed ofa hematologist, dermatologist, pharmacist, and nurse. Her symptoms resolved on day 40.

  1. Phase II study of tosedostat with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukaemia or high-risk MDS.

    PubMed

    Mawad, Raya; Becker, Pamela S; Hendrie, Paul; Scott, Bart; Wood, Brent L; Dean, Carol; Sandhu, Vicky; Deeg, Hans Joachim; Walter, Roland; Wang, Lixia; Myint, Han; Singer, Jack W; Estey, Elihu; Pagel, John M

    2016-01-01

    Tosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission (CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Thirty-four patients ≥60 years old (median age 70 years; range, 60-83) were randomized to receive tosedostat (120 mg on days 1-21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2 /d) or decitabine (20 mg/m2 /d) every 35 d. Twenty-nine patients (85%) had AML, including 15 (44%) with secondary AML/MDS, and 5 (15%) had MDS-refractory anaemia with excess blasts type 2. The CR/CR with incomplete count recovery (CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3-internal tandem duplication mutations. Median follow-up was 11.2 months (range, 0.5-22.3), and median survival was 11.5 months (95% confidence interval, 5.2-16.7). Twenty-three patients (67.6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3-4 non-haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/MDS, results in a CR/CRi rate of >50%, and warrants further study in larger trials. © 2015 John Wiley & Sons Ltd.

  2. Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach.

    PubMed

    Desai, Urja N; Shah, Krupa P; Mirza, Sheefa H; Panchal, Darshil K; Parikh, Sonia K; Rawal, Rakesh M

    2015-01-01

    Acute Myeloid Leukemia (AML) therapy continues to be a daunting challenge. Cytosine Arabinoside (Ara-C) is widely used to treat hematological malignancy in humans, but often becomes ineffective because of increased resistance to the drug which may lead to a worse prognosis. Therefore new strategies are needed to understand the mechanism responsible for drug resistance and to develop new therapies to overcome it. Research evidence based on natural compounds used alone or in combination with current chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin and Silibinin displayed anti-cancer activity against various types of cancers and cell lines and can be used in combination with Cytarabine with the aim to increase cytotoxicy profile and reduction in drug resistance. Experimental Work: Primary cells obtained from AML patient's bone marrow were used to develop in-vitro model and further exposed to various concentration of Cytarabine (10 nM-5000 nM), Hesperidin (0.5 μM-100 μM) and Silibinin (0.5 μM-100 μM) alone and in combination with Cytarabine (Hesperidin-25 μM, Silibinin10 μM) to check cytotoxicity using MTT assay. Synergistic effect was evaluated by Combination Index method. In-vitro study of Hesperidin and Silibinin indicated their cytotoxicity at IC 50 value 50.12 μM and 16.2 μM, respectively. Combination Index study revealed Hesperidin and Silibinin both showed synergistic potential and decreased the IC 50 value of Cytarabine by ~5.9 and ~4.5 folds, respectively. Both natural compounds showed potential anti-leukemic activity hence may be used for AML therapy alone or in combination with other chemotherapeutic agents.

  3. A Randomized Phase 2 Study of Idarubicin and Cytarabine With Clofarabine or Fludarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia

    PubMed Central

    Jabbour, Elias; Short, Nicholas J.; Ravandi, Farhad; Huang, Xuelin; Xiao, Lianchun; Garcia-Manero, Guillermo; Plunkett, William; Gandhi, Varsha; Sasaki, Koji; Pemmaraju, Naveen; Daver, Naval G.; Borthakur, Gautam; Jain, Nitin; Konopleva, Marina; Estrov, Zeev; Kadia, Tapan M.; Wierda, William G.; DiNardo, Courtney D.; Brandt, Mark; O’Brien, Susan M.; Cortes, Jorge E.; Kantarjian, Hagop

    2017-01-01

    BACKGROUND Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine. RESULTS The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CONCLUSIONS CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. PMID:28708931

  4. Liposomal cytarabine in the prophylaxis and treatment of CNS lymphoma: toxicity analysis in a retrospective case series study conducted at Polish Lymphoma Research Group Centers.

    PubMed

    Jurczak, Wojciech; Kroll-Balcerzak, Renata; Giebel, Sebastian; Machaczka, Maciej; Giza, Agnieszka; Ogórka, Tomasz; Fornagiel, Szymon; Rybka, Justyna; Wróbel, Tomasz; Kumiega, Beata; Skotnicki, Aleksander B; Komarnicki, Mieczysław

    2015-04-01

    Lymphomas with primary or secondary involvement of central nervous system (CNS) have poor prognosis despite specific treatment protocols which include whole brain radiotherapy and high-dose systemic and/or intrathecal chemotherapy. Toxicity of intrathecal liposomal cytarabine-based regimens collected between November 2006 and January 2012 was assessed retrospectively. Data from 120 adult lymphoma patients with, or at high risk of CNS involvement who received intrathecal liposomal cytarabine-based regimens at six Polish Lymphoma Research Group centres between November 2006 and January 2012 were assessed retrospectively. Patients were divided into three cohorts: A (high risk of CNS disease, n = 88), B (cerebrospinal fluid pleocytosis without neurological symptoms or pathological imaging findings, n = 7), and C (CNS disease/neurological involvement; n = 25). In all examined groups, toxicity of treatment was found to be acceptable (including the prophylactic setting). None of the patients in cohorts A or B who took intrathecal liposomal cytarabine 50 mg, repeated every 2-4 weeks (mean 3.8 doses) had experienced a CNS relapse at a median follow-up time of 3 years. Patients in cohort C had a 76 % overall neurological response rate (including a 40 % complete response rate) and median overall survival of 4.8 years. Regimens incorporating liposomal cytarabine seem to be safe and effective treatments for lymphomas with CNS involvement.

  5. Alternating R-CHOP and R-cytarabine is a safe and effective regimen for transplant-ineligible patients with a newly diagnosed mantle cell lymphoma.

    PubMed

    Klener, Pavel; Fronkova, Eva; Belada, David; Forsterova, Kristina; Pytlik, Robert; Kalinova, Marketa; Simkovic, Martin; Salek, David; Mocikova, Heidi; Prochazka, Vit; Blahovcova, Petra; Janikova, Andrea; Markova, Jana; Obr, Ales; Berkova, Adela; Kubinyi, Jozef; Vaskova, Martina; Mejstrikova, Ester; Campr, Vit; Jaksa, Radek; Kodet, Roman; Michalova, Kyra; Trka, Jan; Trneny, Marek

    2018-02-01

    Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years. Most patients had intermediate (39.7%) and high-risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography-computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression-free survival and overall survival were 51.3% and 68.6% at 4 years, respectively. Mantle cell lymphoma international prognostic index, bulky disease (≥ 5 cm), and achievement of positron emission tomography-negativity independently correlated with progression-free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R-CHOP and R-cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial (clinicaltrials.gov) NCT03054883. Copyright © 2017 John Wiley & Sons, Ltd.

  6. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia.

    PubMed

    Jabbour, Elias; Short, Nicholas J; Ravandi, Farhad; Huang, Xuelin; Xiao, Lianchun; Garcia-Manero, Guillermo; Plunkett, William; Gandhi, Varsha; Sasaki, Koji; Pemmaraju, Naveen; Daver, Naval G; Borthakur, Gautam; Jain, Nitin; Konopleva, Marina; Estrov, Zeev; Kadia, Tapan M; Wierda, William G; DiNardo, Courtney D; Brandt, Mark; O'Brien, Susan M; Cortes, Jorge E; Kantarjian, Hagop

    2017-11-15

    Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients). Patients received induction with idarubicin and cytarabine, plus either clofarabine or fludarabine. Responding patients could receive up to 6 cycles of consolidation therapy. Outcomes were compared with a historical cohort of patients who received idarubicin and cytarabine. The complete remission/complete remission without platelet recovery rate was similar among patients in the CIA and FIA arms (80% and 82%, respectively). The median event-free survival was 13 months and 12 months, respectively (P = .91), and the median overall survival was 24 months and not reached, respectively (P = .23), in the 2 treatment arms. CIA was associated with more adverse events, particularly transaminase elevation, hyperbilirubinemia, and rash. Early mortality was similar in the 2 arms (60-day mortality rate of 4% for CIA vs 1% for FIA; P = .32). In an exploratory analysis of patients aged <50 years, FIA was found to be associated with improved survival compared with idarubicin and cytarabine (2-year event-free survival rate: 58% vs 30% [P = .05] and 2-year overall survival rate: 72% vs 36% [P = .009]). CIA and FIA have similar efficacy in younger patients with newly diagnosed AML, although FIA is associated with a better toxicity profile. Cancer 2017;123:4430-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

  7. Induction treatment of acute myeloid leukemia in an elderly patient with intramarrow injection/administration of cytarabine. Second case report.

    PubMed

    Islam, Anwarul

    2017-09-01

    We show for the second time that intramarrow injection/administration of chemotherapeutic agents such as cytarabine (Ara-C) can be used safely and effectively and is associated with no toxicity, promising antileukemic activity and possible improved survival.

  8. Liposomal cytarabine in prophylaxis or curative treatment of central nervous system involvement in Burkitt leukemia/lymphoma.

    PubMed

    Segot, Amandine; Raffoux, Emmanuel; Lengline, Etienne; Thieblemont, Catherine; Dombret, Hervé; Boissel, Nicolas; Cluzeau, Thomas

    2015-11-01

    In recent years, the outcome of Burkitt leukemia/lymphoma (BL) has improved significantly. Central nervous system (CNS) involvement continues to be a poor prognostic indicator. High doses of intravenous polychemotherapy, intrathecal chemotherapy, and cranio-spinal radiation therapy are used by numerous groups. Majority of patients are cured after this strategy. The next challenge is to decrease toxicities of treatment, including long-term toxicities secondary to cranio-spinal radiation therapy observed in these cured patients. Liposomal cytarabine could be a good alternative to cranio-spinal radiation therapy as already reported in acute lymphoblastic leukemia. We report here eleven patients treated in our center for BL, with liposomal cytarabine instead of cranio-spinal radiation therapy as prophylactic or curative treatment for CNS involvement. Treatment was safe with no short-term grade >3 adverse events. Moreover, no long-term side effects and no impact on outcome were observed. We conclude that LC could be a good option to decrease short/long-term side effects of cranio-spinal radiation therapy in BL and could be evaluated in a future clinical trial.

  9. Undetected Severe Fetal Myelosuppression following Administration of High-Dose Cytarabine for Acute Myeloid Leukemia: Is More Frequent Surveillance Necessary?

    PubMed Central

    Holland, Marium

    2017-01-01

    Background Cytarabine use during pregnancy carries a 5–7% risk of neonatal cytopenia. We report two cases of fetal myelosuppression following high-dose cytarabine administration for acute myeloid leukemia (AML). Case 1 A 36-year-old G9P6 diagnosed with AML at 21 weeks was monitored for fetal anemia weekly and growth monthly. At 33 weeks (after 2 cycles), BPP was 2/10 and MCA PSV was elevated at 1.51 MoM. Urgent cesarean section was performed. The infant had an initial pH of 6.78 and pancytopenia (hematocrit 13.3%, platelets 3 K/UL, and white blood cell count 2.0 K/UL). Initially transfusion dependent, the neonate had count recovery by 3 weeks. Case 2 A 30-year-old G4P3 with AML at 26 weeks was monitored for fetal anemia twice weekly and growth monthly. At 34 weeks (after cycle 1), she was admitted with neutropenic fever. The fetal MCA PSV was borderline at 1.48 MoM. It improved to 1.38 MoM at 35 weeks but the fetal tracing worsened. At delivery the fetus was found to have a hematocrit of 30%, but with normal platelet and WBC. The fetus did not require any transfusions. Conclusion Cytarabine use during pregnancy may cause neonatal myelosuppression. We recommend monitoring for fetal anemia with MCA Dopplers twice weekly. PMID:29075543

  10. Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial.

    PubMed

    Omuro, Antonio; Chinot, Olivier; Taillandier, Luc; Ghesquieres, Hervé; Soussain, Carole; Delwail, Vincent; Lamy, Thierry; Gressin, Rémy; Choquet, Sylvain; Soubeyran, Pierre; Huchet, Aymeri; Benouaich-Amiel, Alexandra; Lebouvier-Sadot, Sophie; Gyan, Emmanuel; Touitou, Valérie; Barrié, Maryline; del Rio, Monica Sierra; Gonzalez-Aguilar, Alberto; Houillier, Caroline; Delgadillo, Daniel; Lacomblez, Lucette; Tanguy, Marie Laure; Hoang-Xuan, Khê

    2015-06-01

    No standard chemotherapy regimen exists for primary CNS lymphoma, reflecting an absence of randomised studies. We prospectively tested two promising methotrexate-based regimens, one more intensive and a milder regimen, for primary CNS lymphoma in the elderly population, who account for most patients. In this open-label, randomised phase 2 trial, done in 13 French institutions, we enrolled immunocompetent patients who had neuroimaging and histologically confirmed newly diagnosed primary CNS lymphoma, were aged 60 years and older, and had a Karnofsky performance scale score of 40 or more. Participants were stratified by Karnofsky performance scale score (<60 vs ≥60) and treating institution and randomly assigned (1:1) to receive methotrexate (3·5 g/m(2)) with temozolomide (150 mg/m(2)) or methotrexate (3·5 g/m(2)), procarbazine (100 mg/m(2)), vincristine (1·4 mg/m(2)), and cytarabine (3 mg/m(2)). Neither regimen included radiotherapy; both included prophylactic G-CSF and corticosteroids. The primary endpoint was 1-year progression-free survival. Analysis was intent to treat, in a non-comparative phase 2 trial design. This study is registered with ClinicalTrials.gov, number NCT00503594. Between July 16, 2007, and March 25, 2010, 98 patients were enrolled, of whom 95 were randomly assigned and analysed; 48 to methotrexate with temozolomide and 47 to methotrexate, procarbazine, vincristine, and cytarabine. 1-year progression-free survival was 36% (95% CI 22-50) in the methotrexate, procarbazine, vincristine, and cytarabine group and 36% (22-50) in the methotrexate with temozolomide group; median progression-free survival was 9·5 months (95% CI 5·3-13·8) versus 6·1 months (3·8-11·9), respectively. Objective responses were noted in 82% (95% CI 68-92) of patients in the methotrexate, procarbazine, vincristine, and cytarabine group versus 71% (55-84) of patients in the methotrexate with temozolomide group. Median overall survival was 31 months (95% CI 12·2-35·8

  11. Treatment of primary acute myeloid leukemia: results of a prospective multicenter trial including high-dose cytarabine or stem cell transplantation as post-remission strategy.

    PubMed

    Brunet, Salut; Esteve, Jordi; Berlanga, Joan; Ribera, Josep M; Bueno, Javier; Martí, Josep M; Bargay, Joan; Guardia, Ramon; Juliá, Antoni; Granena, Albert; Montserrat, Emili; Sierra, Jorge

    2004-08-01

    To evaluate a regimen of induction and consolidation chemotherapy, followed by a post-remission therapy which depended on age and cytogenetics, in patients with primary acute myeloid leukemia. Two hundred patients up to 60 years old received idarubicin, standard dose cytarabine and etoposide as induction chemotherapy and one consolidation course including intermediate dose cytarabine and mitoxantrone. Subsequently, patients with favorable cytogenetics, [i.e., t(8;21), inv(16)] were scheduled to receive 2 courses of high-dose cytarabine. The remainder were scheduled for allogeneic stem cell transplantation (SCT), if 50 years old or lacking a donor. In patients with favorable cytogenetics the 4-year probabilities of survival and leukemia-free survival (LFS) were 62+/-9% and 41+/-10%, respectively. The results were better in patients with t(8;21). LFS at 4 years in patients 50 years old assigned to auto-SCT had a 4-year LFS of 17+/-9%. Adverse cytogenetics and white blood cell count >or= 20 yen 109/L at diagnosis were associated with lower probability of survival and leukemia-free survival. We confirmed that high-dose cytarabine seems a good option for patients with t(8;21). Autologous and allogeneic SCT led to similar leukemia-free survival in patients

  12. Chidamide in FLT3-ITD positive acute myeloid leukemia and the synergistic effect in combination with cytarabine.

    PubMed

    Li, Xia; Yan, Xiao; Guo, Wenjian; Huang, Xin; Huang, Jiansong; Yu, Mengxia; Ma, Zhixin; Xu, Yu; Huang, ShuJuan; Li, Chenying; Zhou, Yile; Jin, Jie

    2017-06-01

    Chidamide, a novel histone deacetylase inhibitor (HDACi), has been approved for treatment of T-cell lymphomas in multiple clinical trials. It has been demonstrated that chidamide can inhibit cell cycle, promote apoptosis and induce differentiation in leukemia cells, whereas its effect on acute myeloid leukemia (AML) patients with FLT3-ITD mutation has not been clarified. In this study, we found that chidamide specifically induced G0/G1 arrest and apoptosis in FLT3-ITD positive AML cells in a concentration and time-dependent manner. We also found chidamide had the cytotoxicity effect on FLT3-ITD positive and negative AML cells. Moreover, with respect to relapsed/refractory patients, chidamide showed the same effectiveness as that in de novo AML patients. Notably, chidamide synergistically enhanced apoptosis caused by cytarabine. Our results support chidamide alone or combine with cytarabine may be used as an alternative therapeutic choice for AML patients especially those with FLT3-ITD mutation or relapsed/refractory ones. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. The role of nanoparticles in the albumin-cytarabine and albumin-methotrexate interactions.

    PubMed

    Pentak, Danuta; Maciążek-Jurczyk, Małgorzata; Zawada, Zygmunt H

    2017-04-01

    Understanding the interactions which occur between nanomaterials and biomolecules is one of the most important issues in nanotechnology. Determining the properties of nanoparticles obtained through the use of novel methods and defining the scope of their application as drug carriers has important practical significance. Nanoparticles containing methotrexate and cytarabine obtained by a modified reverse-phase evaporation method (mREV) were characterized through the use of the UV/Vis and NMR methods. Obtained results confirmed high degree of analysed drugs encapsulation. The encapsulation efficiencies of cytarabine (AraC) and methotrexate (MTX) in L DPPC/AraC/MTX were found to be 86.30% (AraC) and 86.00% (MTX). The increased permeability of the phospholipid membranes, resulting from physico-chemical properties and the location of the drug, as well as from the physico-chemical properties of the phospholipids themselves, has been confirmed by increase in the length of the T1 relaxation time of protons in the N + (CH 3 ) 3 group. The study of analysed drugs release process from the liposomes has been made for bovine serum albumin, both in the absence (dBSA) and in the presence of fatty acid (BSA). Moreover two types of kinetic models (Bhaskar equation and Rigter-Peppas equation) have been used. Based on the study it has been concluded that mathematical modelling of drug release can be very helpful in speeding up product development and in better understanding the mechanisms controlling drug release from advanced delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Health economic impact of high-dose versus standard-dose cytarabine induction chemotherapy for acute myeloid leukaemia.

    PubMed

    Fedele, P L; Avery, S; Patil, S; Spencer, A; Haas, M; Wei, A

    2014-08-01

    Induction chemotherapy for acute myeloid leukaemia (AML) is one of the most resource-intensive cancer therapies delivered in hospitals. To assess the health resource impact of different chemotherapy approaches for AML commonly used in Australia. A retrospective analysis was undertaken in 63 patients aged 18-55 years with AML given induction with either 7 + 3 (cytarabine 100 mg/m(2) days 1-7 and idarubicin 12 mg/m(2) days 1-3) or HiDAC-3 (high-dose cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7 and idarubicin 12 mg/m(2) days 1-3) chemotherapy. Average costs of hospitalisation, pathology, radiology, chemotherapy and ancillary drugs were calculated and compared with current Victorian casemix funding. Two consolidation approaches, HiDAC (cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7) × either three or four cycles (following 7 + 3) and IcE (idarubicin 12,mg/m(2) days 1-2, cytarabine 100 mg/m(2) × 5 days and etoposide 75 mg/m(2) × 5 days) × 2 cycles (following HiDAC-3) were modelled, using a policy of discharge following completion of chemotherapy with outpatient monitoring. The cost (in AUD) of induction was similar between 7 + 3 ($58,037) and HiDAC-3 ($56,902), with bed day costs accounting for 61-62% of the total expense. Blood bank costs ranked second, accounting for 15%. Accumulated costs for HiDAC consolidation were $44,289 for a three-cycle protocol and $59,052 for four cycles ($14,763 per cycle) versus $31,456 for two cycles of IcE consolidation ($15,728 per cycle). Overall, the classical 7 + 3 → HiDAC approach ($102,326/$117,089 for three or four consolidation cycles) incurs a greater cost than a HiDAC-3 → IcE × 2 approach ($88,358). For patients requiring complete hospitalisation until neutrophil recovery, the estimated costs of treatment will be even higher, ranging between $122,282 for HiDAC-3 → IcE × 2, $153,212 for 7 + 3 → HiDAC × 3 and $184,937 for 7 + 3 → HiDAC × 4. State-based casemix funding for non-complicated AML therapy is

  15. Dose Intensification of Daunorubicin and Cytarabine during Treatment of Adult Acute Lymphoblastic Leukemia: Results of Cancer and Leukemia Group B Study 19802

    PubMed Central

    Stock, Wendy; Johnson, Jeffrey L.; Stone, Richard M.; Kolitz, Jonathan E.; Powell, Bayard L.; Wetzler, Meir; Westervelt, Peter; Marcucci, Guido; DeAngelo, Daniel J.; Vardiman, James W.; McDonnell, Diane; Mrózek, Krzysztof; Bloomfield, Clara D.; Larson, Richard A.

    2014-01-01

    Purpose CALGB 19802, a phase II study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) of adults with acute lymphoblastic leukemia (ALL), and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis. Patients and Methods One hundred sixty-one eligible, previously untreated patients age 16–82 years (median, 40 years) were enrolled; 33 (20%) were ≥60years old. Results One hundred twenty-eight patients (80%) achieved a complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. With a median follow-up of 10.4 years for surviving patients, 5-year DFS was 25% (95% CI, 18–33%) and overall survival (OS) was 30% (95% CI, 23–37%). Patients <60 years who received the 80 mg/m2 dose of daunorubicin had a DFS of 33% (22–44%) and OS of 39% (29–49%) at 5 years. Eighty-four (52%) patients relapsed, including nine (6%) with isolated CNS relapses. Omission of cranial irradiation did not result in higher than historical CNS relapse rates. Conclusion Intensive systemic, oral, and intrathecal methotrexate dosing permitted omission of CNS irradiation. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historical CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets. PMID:22744771

  16. Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia.

    PubMed

    Alexander, Thomas B; Lacayo, Norman J; Choi, John K; Ribeiro, Raul C; Pui, Ching-Hon; Rubnitz, Jeffrey E

    2016-12-01

    Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia. Patients and Methods Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m 2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m 2 and cytarabine 2 g/m 2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1. Results Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m 2 , three at 40 mg/m 2 , six at 55 mg/m 2 , and five at 70 mg/m 2 . The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m 2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m 2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m 2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.

  17. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin in the treatment of secondary hemophagocytic lymphohistiocytosis with classical Hodgkin lymphoma: a case report and review of the literature.

    PubMed

    Hu, Steve; Bansal, Pranshu; Lynch, David; Rojas Hernandez, Cristhiam Mauricio; Dayao, Zoneddy

    2016-12-20

    Hemophagocytic lymphohistiocytosis is becoming an increasingly recognized disorder in adults. Classical Hodgkin lymphoma is a relatively uncommon etiology of hemophagocytic lymphohistiocytosis and may complicate treatment options. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin are discussed here as a treatment regimen. A 66-year-old Hispanic man previously in good health presented with a 1-month history of recurrent fevers, chills, and night sweats and a 3-week history of new onset jaundice. A bone marrow biopsy revealed a normocellular bone marrow with increased histiocytes with areas of hemophagocytic activity. He met five out of eight criteria for hemophagocytic lymphohistiocytosis diagnosis including fevers, pancytopenia, hemophagocytosis, ferritin of 23,292 ng/mL (>500 ng/mL), and soluble-CD25 of 15,330 pg/mL (>1033 pg/mL). A right cervical lymph node biopsy revealed CD15, CD30, MUM-1, and Epstein-Barr virus-encoded small ribonucleic acid-positive cells with morphologic findings of classical Hodgkin lymphoma, lymphocyte-rich subtype. He completed 2 weeks of hemophagocytic lymphohistiocytosis-directed therapy with etoposide and dexamethasone, but then was switched to rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin due to minimal improvement in his pancytopenia and hepatic impairment. He completed one full cycle of rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin with notable improvement in serial hepatic function panels and had an undetectable Epstein-Barr virus viral load. However, he eventually died due to complications of Enterococcus faecalis bacteremia and colonic microperforation in the setting of persistent pancytopenia. This case discusses the challenges facing treatment of adult malignancy-associated hemophagocytic lymphohistiocytosis. Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin may be a viable option for patients with secondary

  18. Sugar-modified poly(propylene imine) dendrimers as drug delivery agents for cytarabine to overcome drug resistance.

    PubMed

    Szulc, Aleksandra; Pulaski, Lukasz; Appelhans, Dietmar; Voit, Brigitte; Klajnert-Maculewicz, Barbara

    2016-11-20

    Maltose-modified poly(propylene imine) glycodendrimers (PPI-m OS) of the 4th generation provide a promising strategy for leukemia treatment. Anticancer therapy with nucleoside analog drugs such as cytarabine (Ara-C) frequently has limited efficacy due to drug resistance, inefficient uptake and accumulation of the drug inside cancer cells where it has to be transformed into the active triphosphate congener. The cationic nature of PPI dendrimers makes it possible to form complexes with nucleotide Ara-C triphosphate forms (Ara-CTP). The aim of this work was to test the concept of applying PPI glycodendrimers as drug delivery devices in order to facilitate the delivery of activated cytarabine to cancer cells to overcome metabolic limitations of the drug. The study has been carried out using 1301 and HL-60 leukemic cell lines as well as peripheral blood mononuclear cells. The results of cytotoxicity and apoptosis assays showed enhanced activity of Ara-C triphosphate form (Ara-CTP) complexed with PPI-m dendrimers in relation to free Ara-C and Ara-CTP against 1301 leukemic cells. Secondly, enhanced uptake and cytotoxicity of Ara-CTP-dendrimers complexes toward 1301 cells with blocked human equilibrative nucleoside transporter - hENT1 suggested that this combination might be a versatile candidate for chemotherapy against resistant acute lymphoblastic leukemia cells with lower expression of hENT1. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. High dose cytarabine and mitoxantrone: an effective induction regimen for high-risk acute myeloid leukemia (AML).

    PubMed

    Larson, Sarah M; Campbell, Nicholas P; Huo, Dezheng; Artz, Andrew; Zhang, Yanming; Gajria, Devika; Green, Margaret; Weiner, Howie; Daugherty, Christopher; Odenike, Olatoyosi; Godley, Lucy A; Hyjek, Elizabeth; Gurbuxani, Sandeep; Thirman, Michael; Sipkins, Dorothy; Van Besien, Koen; Larson, Richard A; Stock, Wendy

    2012-03-01

    Patients with high-risk AML, defined as those with advanced age, relapsed/refractory disease, unfavorable molecular and cytogenetic abnormalities, therapy-related myeloid neoplasm (t-MN) and multiple medical co-morbidities tend to respond poorly to standard cytarabine and daunorubicin induction therapy and have a poor prognosis. We performed a retrospective analysis of an alternative induction regimen using high dose cytarabine (HiDAC) and mitoxantrone (MITO) administered to 78 high-risk patients with AML at The University of Chicago from 2001 to 2008. The primary endpoints of the study were complete remission (CR) rate and death within 30 days of initiation of treatment. The median age was 63 years (range:23-85); 27% of these patients had a Charlson co-morbidity index (CCI) > 2. Forty-three (56%) patients had unfavorable cytogenetics, 28 (37%) had intermediate-risk cytogenetics and 5 (7%) had favorable cytogenetics. The CR rate was 45% and the CRi rate 10%; 7 patients (9%) died during induction. Notably, t-MN and relapsed/refractory patients had CR and induction death rates equivalent to de novo AML patients within this series. In this high risk AML population, HiDAC/MITO induction demonstrated an overall response rate of 55% with a low induction death rate of 9% and allowed 32 (41%) patients to proceed to allogeneic stem cell transplant.

  20. Physicochemical properties of liposomes as potential anticancer drugs carriers. Interaction of etoposide and cytarabine with the membrane: Spectroscopic studies

    NASA Astrophysics Data System (ADS)

    Pentak, Danuta

    2014-03-01

    The interactions between etoposide, cytarabine and 1,2-dihexadecanoyl-sn-glycerol-3-phosphocholine bilayers were studied using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR). These techniques have proven to be a very powerful tool in studying the structure and dynamics of phospholipid bilayers. In particular, DSC can provide information on the phase transition temperature and cooperativity of the lipid molecules in the absence and presence of the drug. Vibrational spectroscopy is well suited to the study of drug-lipid interactions, since it allows for an investigation of the conformation of phospholipid molecules at different levels in lipid bilayers and follows structural changes that occur during the gel to liquid-crystalline phase transition. NMR supported the determination of the main phase transition temperatures (TC) of 1,2-dihexadecanoyl-sn-glycerol-3-phosphocholine (DPPC). The main phase transition temperature (TC) determined by 1H NMR is comparable with values obtained by DSC for all studied liposomes. The location of cytarabine and etoposide in liposomes was also determined by NMR. Atomic force microscopy (AFM) images, acquired immediately after sample deposition on a mica surface, revealed the spherical shape of lipid vesicles.

  1. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network.

    PubMed

    Hermine, Olivier; Hoster, Eva; Walewski, Jan; Bosly, André; Stilgenbauer, Stephan; Thieblemont, Catherine; Szymczyk, Michal; Bouabdallah, Reda; Kneba, Michael; Hallek, Michael; Salles, Gilles; Feugier, Pierre; Ribrag, Vincent; Birkmann, Josef; Forstpointner, Roswitha; Haioun, Corinne; Hänel, Mathias; Casasnovas, René Olivier; Finke, Jürgen; Peter, Norma; Bouabdallah, Kamal; Sebban, Catherine; Fischer, Thomas; Dührsen, Ulrich; Metzner, Bernd; Maschmeyer, Georg; Kanz, Lothar; Schmidt, Christian; Delarue, Richard; Brousse, Nicole; Klapper, Wolfram; Macintyre, Elizabeth; Delfau-Larue, Marie-Hélène; Pott, Christiane; Hiddemann, Wolfgang; Unterhalt, Michael; Dreyling, Martin

    2016-08-06

    Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II-IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II-IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Of 497 patients (median age 55 years [IQR 49-60]) randomised from July 20, 2004, to March 18, 2010, 234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6.1 years (95% CI 5.4-6.4), time to treatment failure was significantly longer in the cytarabine group (median 9.1 years [95% CI 6.3-not reached], 5 year rate 65% [95% CI 57-71]) than in the control group (3.9 years

  2. The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.

    PubMed

    Pastina, B; Early, P J; Bergman, R L; Nettifee, J; Maller, A; Bray, K Y; Waldron, R J; Castel, A M; Munana, K R; Papich, M G; Messenger, K M

    2018-05-15

    The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m 2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg -1 day -1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m 2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs. © 2018 John Wiley & Sons Ltd.

  3. Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML)

    PubMed Central

    Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael

    2014-01-01

    Summary Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. Methods In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n=8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n=16). LY2181308 was administered with a loading dosage of 3 consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m2 was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m2 was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Results Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). Conclusions LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials. PMID:23397500

  4. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML

    PubMed Central

    Cortes, Jorge E.; Hogge, Donna E.; Tallman, Martin S.; Kovacsovics, Tibor J.; Damon, Lloyd E.; Komrokji, Rami; Solomon, Scott R.; Kolitz, Jonathan E.; Cooper, Maureen; Yeager, Andrew M.; Louie, Arthur C.; Feldman, Eric J.

    2014-01-01

    CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission + incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs 51.2%, P = .07), meeting predefined criteria for success (P < .1). Differences in EFS and OS were not statistically significant. A planned analysis of the secondary AML subgroup demonstrated an improved response rate (57.6% vs 31.6%, P = .06), and prolongation of EFS (hazard ratio [HR] = 0.59, P = .08) and OS (HR = 0.46, P = .01). Recovery from cytopenias was slower after CPX-351 (median days to absolute neutrophil count ≥1000: 36 vs 32; platelets >100 000: 37 vs 28) with more grade 3-4 infections but without increase in infection-related deaths (3.5% vs 7.3%) or 60-day mortality (4.7% vs 14.6%), indicating acceptable safety. These results suggest a clinical benefit with CPX-351, particularly among patients with secondary AML, and provide the rationale for a phase 3 trial currently underway in newly diagnosed secondary AML patients. This study is registered at Clinicaltrials.gov as #NCT00788892. PMID:24687088

  5. Histone deacetylase inhibitors reduce differentiating osteoblast-mediated protection of acute myeloid leukemia cells from cytarabine

    PubMed Central

    Sterner, Rosalie M.; Kremer, Kimberly N.; Al-Kali, Aref; Patnaik, Mrinal M.; Gangat, Naseema; Litzow, Mark R.; Kaufmann, Scott H.; Westendorf, Jennifer J.; van Wijnen, Andre J.; Hedin, Karen E.

    2017-01-01

    The bone marrow microenvironment protects acute myeloid leukemia (AML) cells during chemotherapy and is a major factor in relapse. Here, we examined which type(s) of bone marrow cells are responsible for the relapse of AML following treatment with cytarabine (Ara-C), and we identified a means to inhibit this protection. To determine the protective cell type(s), AML cells were treated with Ara-C, and AML cell survival in the presence or absence of osteoblast lineage cells was assessed. Cultured AML cells and patient bone marrow isolates were each significantly protected from Ara-C-induced apoptosis by co-culture with differentiating osteoblasts. Moreover, pretreating differentiating osteoblasts with the histone deacetylase inhibitors (HDACi) vorinostat and panobinostat abrogated the ability of the differentiating osteoblasts to protect AML cells. Together, our results indicate that differentiating osteoblasts have the potential to promote residual AML in the bone marrow following standard chemotherapy and act via a mechanism requiring HDACi-sensitive gene expression. Using HDACi to target the leukemic microenvironment in combination with Ara-C could potentially improve treatment of AML. Moreover, other strategies for manipulating bone marrow osteoblasts may also help eradicate AML cells and reduce relapse. PMID:29212250

  6. Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia.

    PubMed

    Zhao, Hongyu; Xu, Li; Yang, Yongjian; Shao, Jianhua; Chen, Ping; Dong, Xuebin; Gu, Linping; Li, Daqi

    2017-01-01

    To investigate the safety and efficacy of the triple therapy of decitabine, idarubicin, and cytarabine in the treatment of refractory or recurrent acute myeloid leukemia (R/R AML). We conducted a single-center retrospective study in which decitabine treatment was administered prior to full-dose idarubicin and cytarabine (D-IA) for 21 R/R AML patients. After 1 cycle of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21 (9.5%) showed a partial response. There was a 1-month response rate (RR) in 12/21 patients (57.14%); these patients achieved CR after 2 cycles of D-IA. Five of these 12 (40%) patients then received sequential allogeneic stem cell transplantation. At the last follow-up date, 9/21 (42.8%) patients had survived, and 7/21 (33.3%) were in continuous CR. Hematological toxicity and infections were the most prominent toxicities of this regimen. Other toxicities included nausea, vomiting, bleeding, and liver enzyme abnormalities. No mortalities were recorded due to treatment-related toxicity during remission. The combination was well tolerated, and the RR was encouraging. Our study suggests that D-IA may offer a novel and potentially effective treatment regimen for R/R AML patients. © 2017 S. Karger AG, Basel.

  7. Addition of High-Dose Cytarabine to Fludarabine-Based Conditioning for Hematopoietic Stem Cell Transplantation for Treating Fanconi Anemia Patients with Advanced Myeloid Malignancy: A Single-Center Experience and Literature Review.

    PubMed

    Aoki, Takahiro; Koh, Katsuyoshi; Ikeda, Yuhachi; Sekinaka, Yujin; Akiyama, Kosuke; Mori, Makiko; Arakawa, Yuki; Hanada, Ryoji

    2016-09-01

    The complication of Fanconi anemia (FA) with acute leukemia is rare and challenging to treat because of high relapse rates, despite the improved outcome of hematopoietic stem cell transplantation with fludarabine-based conditioning for treating FA patients with hematological abnormalities. We added high-dose cytarabine to fludarabine-based conditioning to promote an enhanced antitumor effect and successfully subjected 4 patients with FA, including 3 with acute leukemia, to hematopoietic stem cell transplantation. All patients remain alive without treatment-related mortality or evidence of disease. Adding high-dose cytarabine to fludarabine-based conditioning may be tolerable and effective for treating FA patients with acute leukemia. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Effective chemomobilization with etoposide and cytarabine (EC regimen) in lymphoma patients: a single-center, retrospective, observational study.

    PubMed

    Koyama, Daisuke; Nishiwaki, Satoshi; Harada, Yasuhiko; Yamamoto, Satomi; Kurahashi, Shingo; Sugimoto, Takumi; Iwasaki, Toshihiro; Sugiura, Isamu

    2017-09-01

    Autologous stem cell transplantation is an important strategy for patients with relapsed or refractory lymphoma. Although various regimens for peripheral blood stem cell collection have been used, the optimal regimen has not yet been established. We aimed to evaluate the mobilization efficacy and safety of the regimen consisted of etoposide and cytarabine (EC regimen). We retrospectively analyzed the clinical data of 46 lymphoma patients who received peripheral blood stem cell mobilization with the EC regimen [etoposide (100 mg/m2/day, days 1-4) and cytarabine (100 mg/m2/day, days 1-4)] at Toyohashi municipal hospital from 2004 to 2013. The median age of the patients was 55 years. The most common underlying diseases were diffuse large B-cell lymphoma (46%) and follicular lymphoma (26%). Three-quarters of patients were in their second complete or partial remission. The median total number of collected CD34+ cells was 10.6 × 106 kg-1. Forty-two patients (91%) yielded at least 2 × 106 kg-1 CD34+ cells within a median of 2 apheresis days, and 33 patients (72%) achieved it with only one apheresis. Successful mobilization was observed in five of six patients who failed to mobilize previously. Although febrile neutropenia occurred in 22 patients (48%), no fatal infection was observed. The EC regimen was highly effective in lymphoma patients, including patients who mobilized poorly with other regimens. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience.

    PubMed

    García-Recio, Marta; Cladera, Antonia; Bento, Leyre; Dominguez, Julia; Ruiz de Gracia, Silvia; Sartori, Francesca; Del Campo, Raquel; García, Lucia; Ballester, Carmen; Gines, Jordi; Bargay, Joan; Sampol, Antonia; Gutiérrez, Antonio

    2017-01-01

    Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20-30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity. Other options are the administration of intrathecal (IT) MTX, cytarabine or liposomal cytarabine (ITLC). Our aim is to analyze the experience of the centers of the Balearic Lymphoma Group (BLG) about the toxicity and efficacy of ITLC in the prophylaxis and therapy of CNS lymphomatosis. We retrospectively reviewed cases from 2005 to 2015 (n = 58) treated with ITLC. Our toxicity results were: 33% headache, 20% neurological deficits, 11% nausea, 9% dizziness, 4% vomiting, 4% fever, 2% transient blindness and 2% photophobia. In the prophylactic cohort (n = 26) with a median follow-up of 55 months (17-81) only 3 CNS relapses (11%) were observed (testicular DLBCL, Burkitt and plasmablastic lymphoma, with a cumulative incidence of 8%, 14% and 20% respectively). In the treatment cohort (n = 32), CSF complete clearance was obtained in 77% cases. Median OS was 6 months (0-16). Death causes were lymphoma progression (19 patients, 79%), treatment toxicity (2 patients) and non-related (3 patients, 12%). Toxicity profile was good especially when concomitant dexamethasone was administered. In the prophylactic cohort the incidence of CNS relapse in DLBCL group was similar to previously reported for HDMTX and much better than IT MTX. A high number of ITLC injections was associated with better rates of CSF clearance, clinical responses, PFS and lower relapses. Survival is still poor in CNS lymphomatosis and new therapeutic approaches are still needed.

  10. Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse.

    PubMed

    Pilorge, Sylvain; Rigaudeau, Sophie; Rabian, Florence; Sarkozy, Clémentine; Taksin, Anne L; Farhat, Hassan; Merabet, Fathia; Ghez, Stéphanie; Raggueneau, Victoria; Terré, Christine; Garcia, Isabelle; Renneville, Aline; Preudhomme, Claude; Castaigne, Sylvie; Rousselot, Philippe

    2014-04-01

    Gemtuzumab ozogamicin (fGO), a humanized anti-CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥ 6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard-dose cytarabine (200 mg/m² /day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty-four patients (median age 68 years) received fGO with cytarabine. Median follow-up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two-year overall survival (OS) was 51% (95% CI: 28-69) and 2 years relapse-free survival (RFS) was 51% (95%CI: 25-72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. Copyright © 2013 Wiley Periodicals, Inc.

  11. Platinum and high-dose cytarabine-based regimens are efficient in ultra high/high-risk chronic lymphocytic leukemia and Richter's syndrome: results of a French retrospective multicenter study.

    PubMed

    Durot, Eric; Michallet, Anne-Sophie; Leprêtre, Stéphane; Le, Quoc-Hung; Leblond, Véronique; Delmer, Alain

    2015-08-01

    Ultra high-risk chronic lymphocytic leukemia (CLL) and Richter's syndrome (RS) usually display a poor prognosis. Platinum and cytarabine-based regimens have not been evaluated in large cohorts of patients with CLL or RS. This retrospective study was aimed to assess the efficacy of these regimens in 75 patients with relapsed/refractory (R/R) CLL or RS. Forty-seven patients had R/R CLL (including 36 ultra high-risk CLL) and 28 had RS. Median age was 62 years (range, 18-79 years). Median number of previous therapies was 3 (range, 1-7), including fludarabine-based regimens (75%) and alemtuzumab (32%), and 61% of patients were refractory to their last treatment. Deletions of chromosomes 17p and 11q were found in 40% and 39% of cases, respectively. The overall response rates were 60% with 24% complete response (CR) in CLL, and 43% with 25% CR in RS. The median progression-free survival and overall survival were 11 and 14.6 months, respectively. Fludarabine refractoriness and 17p deletion were not associated with a poorer outcome. The only factors predicting shorter survival were performance status ≥ 2 (P = 0.04) and albumin level <3.5 g/dL (P = 0.0004). Toxicities were mainly myelosuppression and infectious complications. Platinum and high-dose cytarabine-based regimens provide high response rates in high-risk CLL and in RS. However, these results will be challenged by the new arriving agents at least in non-transformed CLL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Intesive fludarabine-high dose cytarabine-idarubicin combination as induction therapy with risk-adapted consolidation may improve treatment efficacy in younger Acute Myeloid Leukemia (AML) patients: Rationales, evidences and future perspectives.

    PubMed

    Guolo, Fabio; Minetto, Paola; Clavio, Marino; Miglino, Maurizio; Lemoli, Roberto Massimo; Gobbi, Marco

    2017-03-22

    Acute Myeloid Leukemia (AML) is the commonest form of leukemia in the adults, with an incidence of 3-4 cases per 100,000 people/year. After the first description of the effective cytarabine + antracycline (3+7) induction regimen, in the last 3 decades, no effective targeted drug has been included in the standard treatment of AML. Many efforts of modifying 3+7 adding a third drug or increasing the dose of anthracycline, cytarabine or both did not lead to substantial improvements, mainly due to increased toxicity. Many in vitro and in vivo evidences suggested that fludarabine may increase efficacy of cytarabine through a synergistic effect. Considering the continuous improvements in supportive care and management of infectious complications the feasibility of more intensive induction strategies have increased and a renewed interest in fludarabine-containing induction strategies arose. The recent MRC AML 15 trial has shown that a fludarabine-containing induction, FLAG-Ida, resulted superior to conventional 3+7 in terms of complete remission rates, relapse incidence and survival, although only a minority of patients could complete the whole planned consolidation program due to an excessive hematological toxicity. Our group recently published a 10-year experience with a fludarabine-containing induction that slightly differed from the MRC one and resulted in good efficacy and higher feasibility. In this commentary we review the major evidences supporting the employ of a fludarabine-containing induction in AML, and discuss the future perspectives.

  13. Methotrexate-cytarabine-dexamethasone combination chemotherapy with or without rituximab in patients with primary central nervous system lymphoma.

    PubMed

    Sun, Xuefei; Liu, Jing; Wang, Yaming; Bai, Xueyan; Chen, Yuedan; Qian, Jun; Zhu, Hong; Liu, Fusheng; Qiu, Xiaoguang; Sun, Shengjun; Ji, Nan; Liu, Yuanbo

    2017-07-25

    High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen). The patients treated with RMAD had a complete remission rate of 66.7% after induction chemotherapy; this rate was only 33.3% in patients treated with MAD alone (p = .011). The most common grade 1-3 adverse events were similar and included hematologic toxicity, increased aminotransferase levels, and gastrointestinal reactions. Multivariate analysis revealed that rituximab treatment was associated with longer progression-free survival (PFS, p = .005) but not overall survival (OS). Additionally, we observed that elevated serum lactate dehydrogenase was associated with shorter OS and PFS. We retrospectively analyzed 60 immunocompetent patients with newly diagnosed PCNSL at Beijing Tiantan Hospital, Capital Medical University from January 2010 to June 2016. Twenty-four patients received 3-6 courses of 3.5 g/m2 methotrexate on day 1; 0.5-1 g/m2 cytarabine on day 2; and 5-10 mg dexamethasone on days 1, 2 and 3. Thirty-six patients received the same combination plus rituximab 375 mg/m2 on day 0. All patients repeated the treatment every 3 weeks. High-dose methotrexate based chemotherapy with rituximab yields a higher complete remission rate and does not increase serious toxicities. PFS benefits from the addition of rituximab. OS has an increasing trend in patients treated with rituximab without statistical significance.

  14. [Liposomal cytarabine for the treatment of leptomeningeal dissemination of central nervous system tumours in children and adolescents].

    PubMed

    Moreno, Lucas; García Ariza, Miguel Angel; Cruz, Ofelia; Calvo, Carlota; Fuster, Jose Luis; Salinas, Jose Antonio; Moscardo, Cristina; Portugal, Raquel; Merino, Jose Manuel; Madero, Luis

    2016-11-01

    Leptomeningeal dissemination in paediatric central nervous system (CNS) tumours is associated with a poor outcome, and new therapeutic strategies are desperately needed. One of the main difficulties in the treatment of CNS tumours is blood brain barrier penetration. Intrathecal therapy has shown to be effective in several paediatric tumours. The aim of this article is to review the data available on the use of liposomal cytarabine for paediatric patients with leptomeningeal dissemination of CNS tumours, including the pharmacology, administration route, safety and efficacy data. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Binding of released Bim to Mcl-1 is a mechanism of intrinsic resistance to ABT-199 which can be overcome by combination with daunorubicin or cytarabine in AML cells

    PubMed Central

    Niu, Xiaojia; Zhao, Jianyun; Ma, Jun; Xie, Chengzhi; Edwards, Holly; Wang, Guan; Caldwell, J. Timothy; Xiang, Shengyan; Zhang, Xiaohong; Chu, Roland; Wang, Zhihong; Lin, Hai; Taub, Jeffrey W.; Ge, Yubin

    2016-01-01

    Purpose To investigate the molecular mechanism underlying intrinsic resistance to ABT-199. Experimental Design Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine or daunorubicin. Immunoprecipitation of Bim and Mcl-1 were used to determine the effect of ABT-199 treatment on their interactions with Bcl-2 family members. Lentiviral shRNA knockdown of Bim and CRISPR knockdown of Mcl-1 were used to confirm their role in resistance to ABT-199. JC-1 assays and flow cytometry were used to determine drug-induced apoptosis. Results Immunoprecipitation of Bim from ABT-199 treated cell lines and a primary patient sample demonstrated decreased association with Bcl-2, but increased association with Mcl-1 without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein, unchanged or decreased Mcl-1 transcript levels, and increased Mcl-1 protein half-life, suggesting that the association with Bim plays a role in stabilizing Mcl-1 protein. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage along with decreased Mcl-1 protein levels, compared to ABT-199 alone, and synergistic induction of cell death in both AML cell lines and primary patient samples obtained from AML patients at diagnosis. Conclusions Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. PMID:27103402

  16. High-dose cytarabine as salvage therapy for relapsed or refractory acute myeloid leukemia--is more better or more of the same?

    PubMed

    Wolach, Ofir; Itchaki, Gilad; Bar-Natan, Michal; Yeshurun, Moshe; Ram, Ron; Herscovici, Corina; Shpilberg, Ofer; Douer, Dan; Tallman, Martin S; Raanani, Pia

    2016-03-01

    Cytarabine is the backbone of most chemotherapeutic regimens for acute myeloid leukemia (AML), yet the optimal dose for salvage therapy of refractory or relapsed AML (RR-AML) has not been established. Very high dose single-agent cytarabine at 36 g/m(2) (ARA-36) was previously shown to be effective and tolerable in RR-AML. In this retrospective analysis, we aim to describe the toxicity and efficacy of ARA-36 as salvage therapy for patients with AML who are primary refractory to intensive daunorubicin-containing induction or those relapsing after allogeneic stem cell transplant (alloSCT). Fifteen patients, median age 53 years, were included in the analysis. Six patients were treated for induction failure, one had resistant APL, and eight relapsed after alloSCT. Complete remission was achieved in 60% of patients. Surviving patients were followed for a median of 8.5 months. One-year overall survival was 54% (95% CI 30%-86%), and relapse rate from remission (n = 9) was 56%. Grade III/IV pulmonary, infectious, ocular and gastrointestinal toxicities occurred in 26%, 20%, 20% and 20% of patients respectively. Salvage therapy with ARA-36 regimen for RR-AML has considerable efficacy with manageable toxicity in patients with induction failure or post-transplant relapse. Overall survival in these high-risk patients still remains poor. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.

    PubMed

    Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Torri, Valter; Fox, Christopher P; Rosée, Paul La; Schorb, Elisabeth; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Ferrari, Angela; Linton, Kim M; Rudà, Roberta; Binder, Mascha; Pukrop, Tobias; Balzarotti, Monica; Fabbri, Alberto; Johnson, Peter; Gørløv, Jette Sønderskov; Hess, Georg; Panse, Jens; Pisani, Francesco; Tucci, Alessandra; Stilgenbauer, Stephan; Hertenstein, Bernd; Keller, Ulrich; Krause, Stefan W; Levis, Alessandro; Schmoll, Hans J; Cavalli, Franco; Finke, Jürgen; Reni, Michele; Zucca, Emanuele; Illerhaus, Gerald

    2016-05-01

    Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article. For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with Clinical

  18. Homoharringtonine combined with aclarubicin and cytarabine synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein.

    PubMed

    Cao, Jiang; Feng, Hao; Ding, Ning-Ning; Wu, Qing-Yun; Chen, Chong; Niu, Ming-Shan; Chen, Wei; Qiu, Ting-Ting; Zhu, Hong-Hu; Xu, Kai-Lin

    2016-11-01

    Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO-1 and Kasumi-1 cells. HAA caused cleavage of the AML1-ETO (AE) oncoprotein to form truncated AE (ΔAE). Pretreatment with the caspase-3 inhibitor caspase-3 inhibitor Q-DEVD-OPh (QDO) not only suppressed HAA-induced apoptosis but also abrogated the cleavage of AE and generation of ΔAE. These results suggest that HAA synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein, thus providing direct evidence for the strong activity of HAA toward t(8;21) AML. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Binding of Released Bim to Mcl-1 is a Mechanism of Intrinsic Resistance to ABT-199 which can be Overcome by Combination with Daunorubicin or Cytarabine in AML Cells.

    PubMed

    Niu, Xiaojia; Zhao, Jianyun; Ma, Jun; Xie, Chengzhi; Edwards, Holly; Wang, Guan; Caldwell, J Timothy; Xiang, Shengyan; Zhang, Xiaohong; Chu, Roland; Wang, Zhihong J; Lin, Hai; Taub, Jeffrey W; Ge, Yubin

    2016-09-01

    To investigate the molecular mechanism underlying intrinsic resistance to ABT-199. Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine or daunorubicin. Immunoprecipitation of Bim and Mcl-1 were used to determine the effect of ABT-199 treatment on their interactions with Bcl-2 family members. Lentiviral short hairpin RNA knockdown of Bim and CRISPR knockdown of Mcl-1 were used to confirm their role in resistance to ABT-199. JC-1 assays and flow cytometry were used to determine drug-induced apoptosis. Immunoprecipitation of Bim from ABT-199-treated cell lines and a primary patient sample demonstrated decreased association with Bcl-2, but increased association with Mcl-1 without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein, unchanged or decreased Mcl-1 transcript levels, and increased Mcl-1 protein half-life, suggesting that the association with Bim plays a role in stabilizing Mcl-1 protein. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage along with decreased Mcl-1 protein levels, compared with ABT-199 alone, and synergistic induction of cell death in both AML cell lines and primary patient samples obtained from AML patients at diagnosis. Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. Clin Cancer Res; 22(17); 4440-51. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Nanoassemblies from amphiphilic cytarabine prodrug for leukemia targeted therapy.

    PubMed

    Liu, Jing; Zhao, Dujuan; He, Wenxiu; Zhang, Huiyuan; Li, Zhonghao; Luan, Yuxia

    2017-02-01

    The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH 2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared. The results of MTT assays on FR-positive K562 cells and FR-negative A549 cells demonstrated higher cytotoxicity of HA-Ara NAs than the native drug. Especially, the IC 50 values revealed that NAs/FA-BSA was 3 and 2-fold effective than non-targeted NAs after 24 and 48h treatment with K562 cells, respectively indicating FR-mediated enhanced anti-tumor efficacy. In vitro cellular uptake, larger accumulation of HA-Ara NAs were observed in comparative with the free FITC and the results further confirmed the selective uptake of NAs/FA-BSA in folate receptor enriched cancer cells. Above all, self-assembled HA-Ara NAs exhibited potential superiority for Ara-C delivery and FA-modified NAs would be an excellent candidate for targeting leukemia therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. HPLC-MS/MS method for the simultaneous determination of MB07133 and its metabolites, cytarabine and arabinofuranosyluracil, in rat plasma.

    PubMed

    Wang, Dan; Xiao, Qingqing; Yang, Wanqiu; Qian, Wei; Yang, Jin

    2016-02-20

    MB07133 is an intravenously administered cytarabine mononucleotide (araCMP) prodrug, for the treatment of hepatocellular carcinoma (HCC). A simple, selective and sensitive HPLC-MS/MS method using high pressure liquid chromatography (HPLC) coupled to triple-quadrupole mass spectrometer, was developed and validated for the detection of prodrug MB07133 and its metabolites, cytarabine (araC) and arabinofuranosyluracil (araU) in rat plasma. Protein precipitation using 3% trichloroacetic acid (TCA) was employed to extract analytes from 100μL rat plasma. Adequate separation of araC and araU from their endogenous compounds was achieved on the Synergi(®) fusion-RP column (150mm×4.6mm, 4μm) by a gradient-elution with a mobile phase consisting of ammonium formate (1mM) and methanol at a flow rate of 1mL/min. Multiple reaction monitoring mode (MRM) was applied in the detection of MB07133, araC, araU and Ganciclovir (internal standard) with ion pairs 441.2/330.2, 244.2/112.2, 245.2/113.2 and 256.1/152.2, respectively. The assays were validated with respect to specificity, linearity (100-50000ng/mL for MB07133, 2-1000ng/mL for araC and araU), accuracy and precision, extraction recovery, matrix effect and stability. The validated method has been successfully applied to an intravenous bolus pharmacokinetic study of MB07133 in male Sprague-Dawley rats (18mg/kg i.v.). Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: Final results and long term outcome of a phase II multicenter clinical trial.

    PubMed

    Candoni, Anna; Papayannidis, Cristina; Martinelli, Giovanni; Simeone, Erica; Gottardi, Michele; Iacobucci, Ilaria; Gherlinzoni, Filippo; Visani, Giuseppe; Baccarani, Michele; Fanin, Renato

    2018-05-01

    The aim of this prospective clinical trial was to evaluate the efficacy and safety of a combination of Gemtuzumab-Ozogamicin (GO) and FLAI scheme (fludarabine, cytarabine, idarubicin) as a first-line therapy in CD33 positive AML. We treated 130 patients, aged <65, with a median age of 52 years. FLAI-GO induction regimen included fludarabine (30 mg/sqm) and cytarabine (2 g/sqm) on days 1-5; idarubicin (10 mg/sqm) on days 1, 3, and 5; and GO (3 mg/sqm) on day 6. SCT was planned for all high-risk AML patients, after consolidation with intermediate doses of cytarabine and idarubicin and a high dose of cytarabine. CD33 expression exceeded 20% in all cases. Primary endpoints of the study included feasibility, overall response rate (ORR) and toxicity. Secondary endpoints included the evaluation of MRD by WT1 expression, feasibility and outcome of consolidation with SCT, overall survival (OS) and disease-free survival (DFS). After induction with FLAI-GO, complete remission (CR) rate was 82%. Four patients achieved partial remission (PR) and 12% were resistant (ORR 85%); death during induction (DDI) was 3%. The hematological and extra hematological toxicity of FLAI-GO was manageable; 45% of patients experienced transient and reversible GO infusion related adverse events. In the setting of patients who achieved a cytological CR after FLAI-GO, the mean of WT1 copies dropped from 8337±9936 copies/10 4 ABL (diagnosis) to 182 ± 436 copies after induction therapy (p = 0.0001) showing a very good disease debulking. After a median follow-up of 54 months, 67/130 (52%) patients were alive. The probability of 1, 2, and 5-year OS was 80%, 63%, and 52%, respectively. The probability of 1, 2, and 5-year DFS was 77%, 58%, and 52%, respectively. Allogeneic and autologous SCT was performed in 60 (46%) and 23 (18%) patients, respectively. In summary, the final results of this trial confirm that FLAI-GO is an active and safe treatment strategy for CD33-positive AML patients aged

  3. Paracetamol and cytarabine binding competition in high affinity binding sites of transporting protein

    NASA Astrophysics Data System (ADS)

    Sułkowska, A.; Bojko, B.; Równicka, J.; Sułkowski, W. W.

    2006-07-01

    Paracetamol (acetaminophen, AA) the most popular analgesic drug is commonly used in the treatment of pain in patients suffering from cancer. In our studies, we evaluated the competition in binding with serum albumin between paracetamol (AA) and cytarabine, antyleukemic drug (araC). The presence of one drug can alter the binding affinity of albumin towards the second one. Such interaction can result in changing of the free fraction of the one of these drugs in blood. Two spectroscopic methods were used to determine high affinity binding sites and the competition of the drugs. Basing on the change of the serum albumin fluorescence in the presence of either of the drugs the quenching ( KQ) constants for the araC-BSA and AA-BSA systems were calculated. Analysis of UV difference spectra allowed us to describe the changes in drug-protein complexes (araC-albumin and AA-albumin) induced by the presence of the second drug (AA and araC, respectively). The mechanism of competition between araC and AA has been proposed.

  4. Carboplatin instead of cisplatin in combination with dexamethasone, high-dose cytarabine with or without rituximab (DHAC+/-R) is an effective treatment with low toxicity in Hodgkin's and non-Hodgkin's lymphomas.

    PubMed

    Tessoulin, B; Thomare, P; Delande, E; Moynard, J; Gastinne, T; Moreau, A; Bossard, C; Mahé, B; Blin, N; Dubruille, V; Touzeau, C; Boudreault, J S; Perrin, F; Lok, A; Guillaume, T; Garnier, A; Peterlin, P; Gallas, P; Chevallier, P; Moreau, P; Le Gouill, Steven

    2017-06-01

    The DHAP regimen (high-dose cytarabine in combination with dexamethasone and cisplatin) with or without rituximab (DHAP+/-R) is one of the most common regimens in daily practice. It is considered the standard treatment for relapse or refractory Hodgkin's and non-Hodgkin's lymphoma (NHL). Cisplatin nephrotoxicity is a major concern, and other platinum compounds are being tried. We performed a monocentric retrospective analysis to evaluate the use of carboplatin, so-called DHAC+/-R regimen. The purpose was to assess the toxicity of the DHAC+/-R regimen in real-life. The Dexamethasone, Cytarabine, Carboplatin (DHAC) regimen consisted of carboplatin AUC = 5 mg/ml/min (targeted area under the curve with Calvert's formula) on day 1, cytarabine 2 g/m 2 twice a day on day 2 and IV dexamethasone 40 mg from days 1 to 4. Rituximab was administrated at 375 mg/m 2 on day 1 for CD20+ NHL. The interval between courses was 21 days. During the period considered, 199 patients received DHAC+/-R. For the entire cohort, median follow-up is 24 months (range, 2-82), median OS is not reached (NR), estimated 2-year OS is 75% (95% CI, 69-83) and median progression-free survival (PFS) is 46 months (95% CI, 22-NA). Of 144 patients scheduled for autologous stem cell transplantation (ASCT), 102 (71%, NA = 2) were in response after DHAC+/-R and all except 4 underwent ASCT. Grade ≥ 3 haematological toxicities were mainly thrombocytopenia (n = 101) and anaemia (n = 95). Grade ≥ 3 neutropenia occurred in 10 patients. No grade ≥ 3 renal and one grade 3 neurological toxicity were reported. DHAC+/-R is feasible in daily practice, provides good response rates and jeopardises neither stem cell collection nor ASCT.

  5. Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia.

    PubMed

    Gabor, Krisztina Mita; Schermann, Geza; Lautner-Csorba, Orsolya; Rarosi, Ferenc; Erdelyi, Daniel J; Endreffy, Emoke; Berek, Krisztina; Bartyik, Katalin; Bereczki, Csaba; Szalai, Csaba; Semsei, Agnes F

    2015-04-01

    Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara-C are associated with toxicity and clinical outcome in a patient population with childhood ALL. We studied 8 SNPs in the CDA, DCK, DCTD, SLC28A3, and SLC29A1 genes in 144 patients with childhood acute lymphoblastic leukemia treated according to ALLIC BFM 1990, 1995 and 2002 protocols. DCK rs12648166 and DCK rs4694362 SNPs were associated with hematologic toxicity (OR = 2.63, CI 95% = 1.37-5.04, P = 0.0036 and OR = 2.53, CI 95% = 1.34-4.80, P = 0.0044, respectively). Our results indicate that DCK polymorphisms might be important genetic risk factors for hematologic toxicity during ALL treatment with ara-C. Individualized chemotherapy based on genetic profiling may help to optimize ara-C dosing, leading to improvements in clinical outcome and reduced toxicity. © 2015 Wiley Periodicals, Inc.

  6. [Natural factors influencing sleep].

    PubMed

    Jurkowski, Marek K; Bobek-Billewicz, Barbara

    2007-01-01

    Sleep is a universal phenomenon of human and animal lives, although the importance of sleep for homeo-stasis is still unknown. Sleep disturbances influence many behavioral and physiologic processes, leading to health complications including death. On the other hand, sleep improvement can beneficially influence the course of healing of many disorders and can be a prognostic of health recovery. The factors influencing sleep have different biological and chemical origins. They are classical hormones, hypothalamic releasing and inhibitory hormones, neuropeptides, peptides and others as cytokines, prostaglandins, oleamid, adenosine, nitric oxide. These factors regulate most physiologic processes and are likely elements integrating sleep with physiology and physiology with sleep in health and disorders.

  7. RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia.

    PubMed

    Abraham, Ajay; Varatharajan, Savitha; Karathedath, Sreeja; Philip, Chepsy; Lakshmi, Kavitha M; Jayavelu, Ashok Kumar; Mohanan, Ezhilpavai; Janet, Nancy Beryl; Srivastava, Vivi M; Shaji, Ramachandran V; Zhang, Wei; Abraham, Aby; Viswabandya, Auro; George, Biju; Chandy, Mammen; Srivastava, Alok; Mathews, Vikram; Balasubramanian, Poonkuzhali

    2015-07-01

    Variation in terms of outcome and toxic side effects of treatment exists among acute myeloid leukemia (AML) patients on chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Candidate Ara-C metabolizing gene expression in primary AML cells is proposed to account for this variation. Ex vivo Ara-C sensitivity was determined in primary AML samples using MTT assay. mRNA expression of candidate Ara-C metabolizing genes were evaluated by RQPCR analysis. Global gene expression profiling was carried out for identifying differentially expressed genes between exvivo Ara-C sensitive and resistant samples. Wide interindividual variations in ex vivo Ara-C cytotoxicity were observed among samples from patients with AML and were stratified into sensitive, intermediately sensitive and resistant, based on IC50 values obtained by MTT assay. RNA expression of deoxycytidine kinase (DCK), human equilibrative nucleoside transporter-1 (ENT1) and ribonucleotide reductase M1 (RRM1) were significantly higher and cytidine deaminase (CDA) was significantly lower in ex vivo Ara-C sensitive samples. Higher DCK and RRM1 expression in AML patient's blast correlated with better DFS. Ara-C resistance index (RI), a mathematically derived quotient was proposed based on candidate gene expression pattern. Ara-C ex vivo sensitive samples were found to have significantly lower RI compared with resistant as well as samples from patients presenting with relapse. Patients with low RI supposedly highly sensitive to Ara-C were found to have higher incidence of induction death (p = 0.002; RR: 4.35 [95% CI: 1.69-11.22]). Global gene expression profiling undertaken to find out additional contributors of Ara-C resistance identified many apoptosis as well as metabolic pathway genes to be differentially expressed between Ara-C resistant and sensitive samples. This study highlights the importance of evaluating expression of candidate Ara-C metabolizing genes in predicting ex vivo drug response as well as

  8. Modified ESHAP as salvage chemotherapy for recurrent or refractory non-Hodgkin's lymphoma: results of a single-center study of 32 patients. Modified etoposide, methylprednisolone, cytarabine and cisplatin.

    PubMed

    Oztürk, Mehmet Akif; Barişta, Ibrahim; Altundağ, M Kadri; Türker, Alev; Yalçin, Suayib; Celik, Ismail; Güllü, Ibrahim; Güler, Nilüfer; Ozişik, Yavuz; Kars, Ayşe; Kansu, Emin; Baltali, Eşmen; Tekuzman, Gülten

    2002-12-01

    We have evaluated the clinical efficacy and toxicity of a modified etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) chemotherapy regimen that has been used by the Hacettepe University Department of Medical Oncology (Ankara, Turkey) since 1993. Thirty-two patients (18 men and 14 women) with refractory or recurrent non-Hodgkin's lymphoma (NHL) were treated with this protocol. The median age of the patients was 39 years (range 21-66 years). Patients were hospitalized during therapy. On the first day, 2 g/m(2) cytarabine was given, followed on days 2-5 by 60 mg/m(2) etoposide, 500 mg of methylprednisolone and 25 mg/m(2) cisplatin. After two cycles of chemotherapy, clinical efficacy was assessed by clinical examination, chest radiography, ultrasonography and/or computed tomography. The complications were assessed on the basis of the World Health Organization criteria. Nine patients (28%) had a complete response and 8 patients (25%) had a partial response. In responders, the median duration of remission was 6 months. By the end of the first year, 27% of the patients were still disease free and 66% were alive. High serum levels of lactate dehydrogenase had an adverse effect on disease-free survival, but no effect on overall survival (OS). The only unfavorable prognostic factor for OS was the presence of bulky disease. Neutropenia developed in 59% of patients, and febrile neutropenia developed in 74% of these patients, requiring hospitalization for an average of 8 days. Three patients died of neutropenia-associated sepsis despite broad-spectrum antibacterial and antifungal treatment. Thrombocytopenia was detected in 10 patients and anemia in 3 patients; among these, 7 patients with thrombocytopenia and 1 patient with anemia required transfusions. The modified ESHAP regimen induced remission in more than half of the patients with refractory or recurrent NHL. However, the duration of remission was brief. Moreover, significant myelotoxicity was common, and the

  9. Factors influencing twins and zygosity.

    PubMed

    Hankins, Gary V D; Saade, George R

    2005-01-01

    Zygosity is influenced by many factors. Monozygotic twins occur spontaneously in approximately 1 in 250 births and are felt to increase twofold with ovulation induction techniques. Monozygotic twinning also increases in proportion to the number of blastocysts transferred during in vitro fertilisation. In contrast, dizygotic twinning appears to be influenced by race, genetic factors, maternal age, fertility enhancing drugs, folic acid supplementation, and maternal nutritional status.

  10. [Neuron differential attachment purification and its influence factor].

    PubMed

    Li, Jun; Feng, Daxiong; Huang, Yize; Ye, Fei

    2010-02-01

    Neuron purification is essential to procedure of various nerve cell experimental research, however, at present there is few reports on the effect of various factors on neural axons during purification. To find out a simple method of neuron purification, and to investigate the influence factors of corresponding purification culture in dorsal root ganglion (DRG) tissue culture on beta3-tubulin positive axon. The DRGs were obtained from the 3 days neonatal SD rat microscopically and were made into cell suspension. Then, the amount of attached DRG neurons and nonneuronal cells in poly-D-lysine (PDL) group, PDL/Laminin (PDL/LN) group and collagen-I (Col I) group was observed from 10 to 100 minutes. Then, the extension and arborization of beta3-tubulin positive axons were observed after 72 hours completely randomised DRG tissue culture for the research of the influences among culture substrates (PDL, PDL/LN, and Col I), FBS (0, 5%, and 10%), 5 fluorouracil (5-Fu, 0, 20, and 40 micromol/L), and cytarabine (Ara-C, 0, 10, and 20 micromol/L). Adherent cells were observed instantly after inoculation by inverted phase contrast microscope and inverted fluorescence microscope; after cell suspension was removed, adherent growth of DRGn cells and non-DRGn cells were still seen. In PDL group, the amount of NSE negative cells was significantly higher than that of NSE positive cells at 10 and 30 minutes (P < 0.05); the amount of NSE positive cells was significantly higher than that of NSE negative cells at 80, 90 and 100 minutes (P < 0.05). In PDL/LN group, there was no significant difference (P > 0.05) in the amount of NSE negative cells and NSE positive cells at 10, 20, 30, 40, and 50 minutes; the amount of NSE positive cells was significantly higher (P < 0.05) than that of NSE negative cells at 60, 70, 80, 90, 100 minutes. In Col I group, the amount of NSE negative cells was higher than that of NSE positive cells at 10-40 minutes, but showing no significant difference (P > 0

  11. A Phase I Study of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.

    PubMed

    Pardee, Timothy S; Anderson, Rebecca G; Pladna, Kristin M; Isom, Scott; Ghiraldeli, Lais P; Miller, Lance D; Chou, Jeff W; Jin, Guangxu; Zhang, Wei; Ellis, Leslie R; Berenzon, Dmitriy; Howard, Dianna S; Hurd, David D; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2018-05-01

    Purpose: CPI-613, a lipoate analogue that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH), has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response and determined the MTD, efficacy, and safety of CPI-613 combined with high-dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. Experimental Design: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models. A phase I study of CPI-613 plus cytarabine and mitoxantrone was conducted in patients with relapsed or refractory AML. Results: Exposure to chemotherapy induced mitochondrial oxygen consumption that depended on PDH. CPI-613 sensitized AML cells to chemotherapy indicating that mitochondrial metabolism is a source of resistance. Loss of p53 did not alter response to CPI-613. The phase I study enrolled 67 patients and 62 were evaluable for response. The overall response rate was 50% (26CR+5CRi/62). Median survival was 6.7 months. In patients over 60 years old, the CR/CRi rate was 47% (15/32) with a median survival of 6.9 months. The response rate for patients with poor-risk cytogenetics also was encouraging with 46% (11/24 patients) achieving a CR or CRi. RNA sequencing analysis of a subset of baseline bone marrow samples revealed a gene expression signature consistent with the presence of B cells in the pretreatment marrow of responders. Conclusions: The addition of CPI-613 to chemotherapy is a promising approach in older patients and those with poor-risk cytogenetics. Clin Cancer Res; 24(9); 2060-73. ©2018 AACR . ©2018 American Association for Cancer Research.

  12. Phase 2 study of low-dose clofarabine plus cytarabine for patients with higher-risk myelodysplastic syndrome who have relapsed or are refractory to hypomethylating agents.

    PubMed

    Jabbour, Elias; Faderl, Stefan; Sasaki, Koji; Kadia, Tapan; Daver, Naval; Pemmaraju, Naveen; Patel, Keyur; Khoury, Joseph D; Bueso-Ramos, Carlos; Bohannan, Zachary; Ravandi, Farhad; Borthakur, Gautam; Verstovsek, Srdan; Miller, Darla; Maduike, Rita; Hosing, Chitra; Kantarjian, Hagop M; Garcia-Manero, Guillermo

    2017-02-15

    The outcome of patients with higher-risk myelodysplastic syndromes (MDS) after hypomethylating agent (HMA) failure is poor. This study evaluated the safety and activity of a combination of low-dose clofarabine and cytarabine for these patients. Seventy patients with higher-risk MDS who had no response, progressed, or relapsed after at least 4 cycles of HMA therapy were treated. The median age was 72 years. Thirty-nine percent of the patients had high-risk disease according to the International Prognostic Scoring System, and 50% of the patients had poor-risk cytogenetics. Twenty-three percent of the patients had therapy-related MDS. The median number of prior cycles of HMA was 6 (range, 4-45). The overall response rate was 44%. The 6-week mortality rate was 9%. Grade 3 and higher nonhematologic toxicities were rare, but infections occurred in 52% of the patients, and fever of unknown origin occurred in 33%. The median overall survival (OS) was 10 months (95% confidence interval, 1-37 months). Thirteen percent of the patients underwent allogeneic stem cell transplantation. The responding patients had a median OS of 22 months, whereas the nonresponding patients had a median OS of 4 months. A complex karyotype was associated with worse response rates and OS. The combination of low-dose clofarabine and cytarabine is clinically active in these patients with few treatment options. Cancer 2017;123:629-637. © 2016 American Cancer Society. © 2016 American Cancer Society.

  13. The topoisomerase II inhibitor voreloxin causes cell cycle arrest and apoptosis in myeloid leukemia cells and acts in synergy with cytarabine

    PubMed Central

    Walsby, Elisabeth J.; Coles, Steven J.; Knapper, Steven; Burnett, Alan K.

    2011-01-01

    Background Topoisomerase II is essential for the maintenance of DNA integrity and the survival of proliferating cells. Topoisomerase II poisons, including etoposide and doxorubicin, inhibit enzyme-mediated DNA ligation causing the accumulation of double-stranded breaks and have been front-line drugs for the treatment of leukemia for many years. Voreloxin is a first-in-class anti-cancer quinolone derivative that intercalates DNA and inhibits topoisomerase II. The efficacy and mechanisms of action of voreloxin in acute myeloid leukaemia were addressed in this study. Design and Methods Primary acute myeloid leukemia blasts (n = 88) and myeloid cell lines were used in vitro to study voreloxin through viability assays to assess cell killing and synergy with other drugs. Apoptosis and cell cycling were assessed by flow cytometry. DNA relaxation assays were utilized to determine that voreloxin was active on topoisomerase II. Results The mean lethal dose 50% (LD50) (± standard deviation) of voreloxin for primary acute myeloid leukemia blasts was 2.30 μM (± 1.87). Synergy experiments between voreloxin and cytarabine identified synergism in 22 of 25 primary acute myeloid leukemia samples tested, with a mean combination index of 0.79. Apoptosis was shown to increase in a dose-dependent manner. Furthermore, voreloxin was active in the p53-null K562 cell line suggesting that the action of voreloxin is not affected by p53 status. The action of voreloxin on topoisomerase II was confirmed using a DNA relaxation assay. Conclusions Voreloxin may provide an interesting addition to the cache of drugs available for the treatment of acute myeloid leukemia, a disease with a poor long-term survival. In addition to its potent action as a single agent in dividing cells, the synergy we demonstrated between voreloxin and cytarabine recommends further investigation of this topoisomerase II inhibitor. PMID:21134979

  14. Cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) combination sequential chemotherapy for advanced diffuse histiocytic lymphoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sweet, D.L.; Golomb, H.M.; Ultmann, J.E.

    A program of combination sequential chemotherapy using cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (COMLA) was administered to 42 previously untreated patients with advanced diffuse histiocytic lymphoma. Twenty-three patients achieved a complete remission as determined by strict clinical restaging criteria. The observed median duration of survival for the complete responders is longer than 33 months. Eight patients achieved a partial response, with a median survival longer than 21 months. Eleven patients showed no response, with a median survival of 5 months. Toxicity was acceptable. None of the responders have shown central nervous system relapse. There was no difference inmore » response rates between patients with stage III or IV lymphoma or between asymptomatic or symptomatic patients. The COMLA program produces a high rate of complete and durable remissions and should be considered as an initial form of management of patients with advanced diffuse histiocytic lymphoma.« less

  15. Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

    PubMed

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

    1990-02-28

    Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

  16. Phonological Awareness: Factors of Influence

    ERIC Educational Resources Information Center

    Frohlich, Linda Paulina; Petermann, Franz; Metz, Dorothee

    2013-01-01

    Early child development is influenced by various genetic and environmental factors. This study aims to identify factors that affect the phonological awareness of preschool and first grade children. Based on a sample of 330 German-speaking children (mean age = 6.2 years) the following domains were evaluated: Parent factors, birth and pregnancy,…

  17. Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study.

    PubMed

    Houillier, Caroline; Ghesquières, Hervé; Chabrot, Cécile; Soussain, Carole; Ahle, Guido; Choquet, Sylvain; Nicolas-Virelizier, Emmanuelle; Bay, Jacques-Olivier; Vargaftig, Jacques; Gaultier, Claude; Touitou, Valérie; Martin-Duverneuil, Nadine; Cassoux, Nathalie; Le Garff-Tavernier, Magali; Costopoulos, Myrto; Faurie, Pierre; Hoang-Xuan, Khê

    2017-06-01

    Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m 2 D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m 2 D1-2). Addition of rituximab (375 mg/m 2 D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.

  18. Increased non-relapse mortality due to high-dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults.

    PubMed

    Arai, Yasuyuki; Kondo, Tadakazu; Shigematsu, Akio; Tanaka, Junji; Ohashi, Kazuteru; Fukuda, Takahiro; Kawakita, Toshiro; Mori, Takehiko; Hoshino, Takumi; Onizuka, Makoto; Ozawa, Yukiyasu; Yoshida, Shuro; Ueda, Yasunori; Mizuno, Ishikazu; Atsuta, Yoshiko; Mizuta, Shuichi

    2017-07-01

    The efficacy of high-dose cytarabine (HDCA) plus cyclophosphamide/total-body irradiation (CY/TBI) has been proved in cord blood transplantation (CBT) for acute lymphoblastic leukaemia (ALL), but not in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT). In this cohort study, we compared the prognosis of CY/TBI (N = 1244) and HDCA/CY/TBI (N = 316) regimens in BMT/PBSCT for ALL. The addition of HDCA decreased post-transplant relapse, while significantly increasing non-relapse mortality (risk ratio, 1·33), and overall survival was not improved. The positive effects of HDCA reported in CBT cannot be extrapolated to BMT/PBSCT, and HDCA may not be recommended in these procedures. © 2017 John Wiley & Sons Ltd.

  19. Factors that Influence Participation in Online Learning

    ERIC Educational Resources Information Center

    Vonderwell, Selma; Zachariah, Sajit

    2005-01-01

    This study explored what factors influenced learner participation in two sections of a graduate online course at a Midwestern university. Findings indicated that online learner participation and patterns of participation are influenced by the following factors: technology and interface characteristics, content area experience, student roles and…

  20. Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment of xenografted glioma.

    PubMed

    Qi, Na; Cai, Cuifang; Zhang, Wei; Niu, Yantao; Yang, Jingyu; Wang, Lihui; Tian, Bin; Liu, Xiaona; Lin, Xia; Zhang, Yu; Zhang, Yan; He, Haibing; Chen, Kang; Tang, Xing

    2014-09-10

    This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Tunneling nanotube (TNT) formation is downregulated by cytarabine and NF-κB inhibition in acute myeloid leukemia (AML)

    PubMed Central

    Omsland, Maria; Bruserud, Øystein; Gjertsen, Bjørn T; Andresen, Vibeke

    2017-01-01

    Acute myeloid leukemia (AML) is a bone marrow derived blood cancer where intercellular communication in the leukemic bone marrow participates in disease development, progression and chemoresistance. Tunneling nanotubes (TNTs) are intercellular communication structures involved in transport of cellular contents and pathogens, also demonstrated to play a role in both cell death modulation and chemoresistance. Here we investigated the presence of TNTs by live fluorescent microscopy and identified TNT formation between primary AML cells and in AML cell lines. We found that NF-κB activity was involved in TNT regulation and formation. Cytarabine downregulated TNTs and inhibited NF-κB alone and in combination with daunorubicin, providing additional support for involvement of the NF-κB pathway in TNT formation. Interestingly, daunorubicin was found to localize to lysosomes in TNTs connecting AML cells indicating a novel function of TNTs as drug transporting devices. We conclude that TNT communication could reflect important biological features of AML that may be explored in future therapy development. PMID:27974700

  2. Factors That Influence Language Growth.

    ERIC Educational Resources Information Center

    McCarthy, Dorothea, Ed.; And Others

    This booklet contains four articles that discuss factors influencing language growth. The first, "The Child's Equipment for Language Growth" by Charlotte Wells, examines what the child needs for language learning, how the child uses his equipment for language growth, and what school factors facilitate the child's use of his equipment for language…

  3. Factors influencing children's food choice.

    PubMed

    Koivisto Hursti, U K

    1999-04-01

    Although food habits are not stable and unchanging during a person's lifetime, a base for healthy food habits can be created in early childhood. Children's food habits can be assumed to be influenced by their parents' food habits and choices. The aim of this article is to review factors influencing food choice in children as well as in adults. The results demonstrate that the development of children's food habits is influenced by a multitude of factors. Parents play an important role in the formation of food habits and preferences of young children. They can influence their children's food choice by making specific foods available, by acting as models for their children and by their behaviour in specific situations. Children tend to be afraid of new foods and do not readily accept them. However, experience is known to enhance preference, and earlier experiences of a particular food are the major determinants of the development of children's food acceptance patterns. Thus, parents should be encouraged to make healthy foods easily available to the child and serve these foods in positive mealtime situations in order to help their child to develop healthy food habits.

  4. Factors influencing children's food choice.

    PubMed

    Hursti, Ulla-Kaisa Koivisto

    1999-01-01

    Although food habits arc not stable and unchanging during a person's lifetime, a base for healthy food habits can be created in early childhood. Children's food habits can be assumed to be influenced by their parents' food habits and choices. The aim of this article is to review factors influencing food choice in children as well as in adults. The results demonstrate that the development of children's food habits is influenced by a multitude of factors. Parents play an important role in the formation of food habits and preferences of young children. They can influence their children's food choice by making specific foods available, by acting as models for their children and by their behaviour in specific situations. Children tend to be afraid of new foods and do not readily accept them. However, experience is known to enhance preference, and earlier experiences of a particular food are the major determinants of the development of children's food acceptance patterns. Thus, parents should be encouraged to make healthy foods easily available to the child and serve these foods in positive mealtime situations in order to help their child to develop healthy food habits.

  5. Factors Influencing Effective Writing.

    ERIC Educational Resources Information Center

    Muccino, Mary Ann; And Others

    Focusing on procedures and strategies suitable for teaching writing to students in grades 4, 6, and 8, this paper examines the factors that have been shown through research to influence effective writing. The paper divides the research examined into the categories of metacognition; socially-based writing strategies; theory-tested approaches to…

  6. Factors influencing perceived angular velocity.

    PubMed

    Kaiser, M K; Calderone, J B

    1991-11-01

    The assumption that humans are able to perceive and process angular kinematics is critical to many structure-from-motion and optical flow models. The current studies investigate this sensitivity, and examine several factors likely to influence angular velocity perception. In particular, three factors are considered: (1) the extent to which perceived angular velocity is determined by edge transitions of surface elements, (2) the extent to which angular velocity estimates are influenced by instantaneous linear velocities of surface elements, and (3) whether element-velocity effects are related to three-dimensional (3-D) tangential velocities or to two-dimensional (2-D) image velocities. Edge-transition rate biased angular velocity estimates only when edges were highly salient. Element velocities influenced perceived angular velocity; this bias was related to 2-D image velocity rather than 3-D tangential velocity. Despite these biases, however, judgments were most strongly determined by the true angular velocity. Sensitivity to this higher order motion parameter was surprisingly good, for rotations both in depth (y-axis) and parallel to the line of sight (z-axis).

  7. Social Factors Influencing Child Health in Ghana

    PubMed Central

    Quansah, Emmanuel; Ohene, Lilian Akorfa; Norman, Linda; Mireku, Michael Osei; Karikari, Thomas K.

    2016-01-01

    Objectives Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals’ target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. Methods ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Results Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Conclusions Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother’s health knowledge is emphasised. PMID:26745277

  8. Social Factors Influencing Child Health in Ghana.

    PubMed

    Quansah, Emmanuel; Ohene, Lilian Akorfa; Norman, Linda; Mireku, Michael Osei; Karikari, Thomas K

    2016-01-01

    Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals' target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother's health knowledge is emphasised.

  9. Factors potentially influencing aminoglycoside use and expenditure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DiPiro, J.T.; Kilsdonk, G.F.; Amerson, A.B.

    1982-07-01

    Factors that may have influenced aminoglycoside use and expenditure in one hospital were examined. Factors that were evaluated as to their influence on aminoglycoside-use patterns were: (1) formulary status; (2) bacterial susceptibility patterns; (3) identified or perceived differences in toxicity; (4) changes in patient population; (5) price paid by the hospital for aminoglycosides; (6) distribution of newsletters or memoranda; (7) advertising and detailing; and (8) pharmacy policies. For FY 1976-77 to 1979-80, the largest proportion of aminoglycoside expense was for gentamicin. During FY 1980-81, the expenditure for gentamicin decreased and tobramycin accounted for the largest proportion of total expenditure. Monthlymore » gentamicin use decreased 20% during FY 1980-81 from the previous year. Tobramycin use increased from January 1979 to November 1980 and decreased from December 1980 to June 1981. Kanamycin use and amikacin use were fairly constant during the study period. Based on temporal relationships, the following factors appeared to influence aminoglycoside use and expenditure: (1) a study conducted at the institution from June 1977 to June 1979 comparing gentamicin and tobramycin nephrotoxicity; (2) a comparative nephrotoxicity study published in a widely circulated medical journal in May 1980; and (3) an intramural newsletter and memorandum distributed in March 1981 encouraging selective aminoglycoside use. The identification of factors that potentially influenced aminoglycoside use can be used to anticipate the future impact of similar events and to devise strategies to influence antimicrobial use.« less

  10. Influence of organizational factors on safety

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haber, S.B.; Metlay, D.S.; Crouch, D.A.

    There is a need for a better understanding of exactly how organizational management factors at a nuclear power plant (NPP) affect plant safety performance, either directly or indirectly, and how these factors might be observed, measured, and evaluated. The purpose of this research project is to respond to that need by developing a general methodology for characterizing these organizational and management factors, systematically collecting information on their status and integrating that information into various types of evaluative activities. Research to date has included the development of the Nuclear Organization and Management Analysis Concept (NOMAC) of a NPP, the identification ofmore » key organizational and management factors, and the identification of the methods for systematically measuring and analyzing the influence of these factors on performance. Most recently, two field studies, one at a fossil fuel plant and the other at a NPP, were conducted using the developed methodology. Results are presented from both studies highlighting the acceptability, practicality, and usefulness of the methods used to assess the influence of various organizational and management factors including culture, communication, decision-making, standardization, and oversight. 6 refs., 3 figs., 1 tab.« less

  11. Factors Influencing Resident Choice of Prosthodontic Residency Program.

    PubMed

    Wojnarwsky, Pandora Keala Lee; Wang, Yan; Shah, Kumar; Koka, Sreenivas

    2017-06-01

    The decision by prosthodontic residency program directors to employ the Match process highlights the need to understand applicant priorities that influence their choice of which programs to rank highly. The purpose of this study is to determine the factors that were most important to residents when choosing from among nonmilitary based prosthodontics dental residency programs in the United States. Following completion of a pilot study, all currently enrolled prosthodontic residents at nonmilitary residency programs were invited to participate via the internet. The study consisted of a survey instrument asking residents to rank 26 possible factors that might impact an applicant's choice of residency program. In addition, the instrument collected other possible influencing variables including gender and debt load. Mean rank scores were compared to determine the most and least important factors. Kruskal-Wallis test was used to compare specific factors between the possible influencing variables. Two hundred and thirty residents completed the survey instrument, representing a 54.1% response rate of possible participants. With regard to factors influencing program choice, reputation of the residency program was the factor ranked the highest by participants, followed in descending order by the program director's personality, curriculum content, access to use of the latest digital technology, and opportunities for dental implant placement. Quality of schools for children, community outreach opportunities, and the ability to moonlight were ranked as the least important factors. Male and female residents ranked factors such as tuition/stipend, curriculum content, and community outreach opportunities significantly differently. Depending on debt load, residents ranked the factors tuition/stipend, ability to moonlight, curriculum content, and safety of the area where the program is differently. Current prosthodontic residents valued the reputation of the program as the most

  12. Successful treatment of systemic juvenile xanthogranulomatosis with cytarabine and 2-chlorodeoxyadenosine: case report and review of the literature.

    PubMed

    Maintz, L; Wenzel, J; Irnich, M; Reinhard, H; Bieber, T

    2017-02-01

    The non-Langerhans cell histiocytosis (LCH) juvenile xanthogranulomatosis (JXG) is usually a benign disease limited to the skin. Only a few cases of systemic disease with at least two affected organs and lethal outcomes have been reported to date. Treatment is controversial and no standard protocol is available. We report the rare case of a 22-month-old boy presenting multiple erythematous brownish papules of the head, trunk and legs, which had developed starting from his 6th month of life. Additional symptoms were delayed psychomotor development, hydrocephalus and hepatosplenomegaly. Further diagnostics revealed a systemic JXG with involvement of the skin, central nervous system, liver and spleen. The patient did not respond to initial therapy with prednisone and vinblastine according to protocol III for LCH. However, further therapy with cytarabine and 2-chlorodeoxyadenosine followed by a consolidation phase with 2-chlorodeoxyadenosine alone was successful and the patient is in his 4th year of remission. We provide a comprehensive review of the reported cases of systemic JXG to date. © 2016 British Association of Dermatologists.

  13. Factors influencing pacing in triathlon

    PubMed Central

    Wu, Sam SX; Peiffer, Jeremiah J; Brisswalter, Jeanick; Nosaka, Kazunori; Abbiss, Chris R

    2014-01-01

    Triathlon is a multisport event consisting of sequential swim, cycle, and run disciplines performed over a variety of distances. This complex and unique sport requires athletes to appropriately distribute their speed or energy expenditure (ie, pacing) within each discipline as well as over the entire event. As with most physical activity, the regulation of pacing in triathlon may be influenced by a multitude of intrinsic and extrinsic factors. The majority of current research focuses mainly on the Olympic distance, whilst much less literature is available on other triathlon distances such as the sprint, half-Ironman, and Ironman distances. Furthermore, little is understood regarding the specific physiological, environmental, and interdisciplinary effects on pacing. Therefore, this article discusses the pacing strategies observed in triathlon across different distances, and elucidates the possible factors influencing pacing within the three specific disciplines of a triathlon. PMID:25258562

  14. Interim 18F-FGD PET/CT may not predict the outcome in primary central nervous system lymphoma patients treated with sequential treatment with methotrexate and cytarabine.

    PubMed

    Jo, Jae-Cheol; Yoon, Dok Hyun; Kim, Shin; Lee, Kyoungmin; Kang, Eun Hee; Park, Jung Sun; Ryu, Jin-Sook; Huh, Jooryung; Park, Chan-Sik; Kim, Jong Hoon; Lee, Sang Wook; Suh, Cheolwon

    2017-09-01

    18 F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17-75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.

  15. Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory lymphoma (2000-2013).

    PubMed

    Gillem, J; Giuffrida, M; Krick, E

    2017-06-01

    Medical records of 22 dogs treated with carboplatin (n = 8) or carboplatin and cytarabine (n = 14) chemotherapy for relapsed or refractory lymphoma between 2000 and 2013 were retrospectively reviewed. The clinical response rate was 18.2% (4/22). Median time to progression was 18 days (56 for responders; 12 for non-responders, P = 0.0006). Median overall survival time was 28 days (109 for responders; 21 for non-responders, P = 0.0007). Thrombocytopenia and neutropenia occurred in 84.2% (16/19) and 52.6% (10/19), respectively. Grade IV thrombocytopenia and neutropenia occurred in 56.3% (9/16) and 60.0% (6/10), respectively. Dogs that received both drugs were more likely to become neutropenic (P = 0.022) or thrombocytopenic (P = 0.001) than dogs receiving carboplatin alone. All responders received both drugs giving a 28.6% (4/14) response rate for the combination. Although some dogs responded to the combination, toxicity was high and the responses were not durable. With adequate supportive care, this protocol may be an acceptable rescue option for some dogs. © 2015 John Wiley & Sons Ltd.

  16. Factors influencing workplace health promotion intervention: a qualitative systematic review.

    PubMed

    Rojatz, Daniela; Merchant, Almas; Nitsch, Martina

    2017-10-01

    Although workplace health promotion (WHP) has evolved over the last 40 years, systematically collected knowledge on factors influencing the functioning of WHP is scarce. Therefore, a qualitative systematic literature review was carried out to systematically identify and synthesize factors influencing the phases of WHP interventions: needs assessment, planning, implementation and evaluation. Research evidence was identified by searching electronic databases (Scopus, PubMed, Social Sciences Citation Index, ASSIA, ERIC, IBBS and PsycINFO) from 1998 to 2013, as well as by cross-checking reference lists of included peer-reviewed articles. The inclusion criteria were: original empirical research, description of WHP, description of barriers to and/or facilitators of the planning, implementation and/or evaluation of WHP. Finally, 54 full texts were included. From these, influencing factors were extracted and summarized using thematic analysis. The majority of influencing factors referred to the implementation phase, few dealt with planning and/or evaluation and none with needs assessment. The influencing factors were condensed into topics with respect to factors at contextual level (e.g. economic crisis); factors at organizational level (e.g. management support); factors at intervention level (e.g. quality of intervention concept); factors at implementer level (e.g. resources); factors at participant level (e.g. commitment to intervention) and factors referring to methodological and data aspects (e.g. data-collection issues). Factors regarding contextual issues and organizational aspects were identified across three phases. Therefore, future research and practice should consider not only the influencing factors at different levels, but also at different phases of WHP interventions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Factors that influence nurses' customer orientation.

    PubMed

    Darby, D N; Daniel, K

    1999-09-01

    Hospital care mostly involves complex processes that are continuously adjusted to match individual client needs. As most patients cannot evaluate the technology used, they focus on personal interactions with care providers when making judgements about the care received. Nurses are the care team members that primarily provide ongoing care. This study aims to further understand factors that influence the way nursing staff relate to their patients. A model is presented of the contextual and self-perceptual factors that influence the level of customer/client orientation of nursing services in an Australian hospital setting along with details of a quantitative study. Nurses completed an anonymous questionnaire, which was then mailed directly to the researchers. Analysis of the data included factor analysis, regression and path analysis. The results show that contextual elements such as management commitment to service quality and self-perceptual factors such as role stress impact on the nurses' client service orientation. However, the variables being studied commonly have both direct and indirect effects with feelings about commitment to the organization having a notable mediating influence. The scales adapted from use in other industries are able to measure the perceptual and outcome variables in a health institutional setting. The managerial implications are that both a comprehensive programme of organizational culture and individual staff member development is needed if an enhanced customer orientation and the consequent improvement in client satisfaction with nursing care is to occur.

  18. Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome.

    PubMed

    Ferrara, Felicetto; Palmieri, Salvatore; Izzo, Tiziana; Criscuolo, Clelia; Riccardi, Cira

    2010-12-01

    Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA-C) ± G-CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA-C as sequential continuous infusion (CI-FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61-81). In patients achieving CR, an additional course, followed by G-CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory to induction treatment. Thirty-four patients (79% of remitters) were eligible for the consolidation and 30 were monitorized for the mobilization of CD34+ cells, collection being successful in 20 of them (67%). Median number of CD34+ cells/kg collected was 6.8 × 10E6. Thirteen patients (20% of the whole population) received ASCT. Median disease free survival (DFS) and overall survival (OS) were 10 and 9 months, respectively. Survival at 5 years is projected to 15%. The only parameter significantly related to either DFS duration or OS duration was unfavourable cytogenetics, which did significantly influence also CR achievement. CI-FLA is effective in elderly patients with AML secondary to previously diagnosed MDS. Best results are achievable in the subgroup of patients with diploid karyotype. Copyright © 2010 John Wiley & Sons, Ltd.

  19. Consideration of Real World Factors Influencing Greenhouse ...

    EPA Pesticide Factsheets

    Discuss a variety of factors that influence the simulated fuel economy and GHG emissions that are often overlooked and updates made to ALPHA based on actual benchmarking data observed across a range of vehicles and transmissions. ALPHA model calibration is also examined, focusing on developing generic calibrations for driver behavior, transmission gear selection and torque converter lockup. In addition, show the derivation of correction factors needed to estimate cold start emission results. To provide an overview of the ALPHA tool with additional focus on recent updates by presenting the approach for validating and calibrating ALPHA to match particular vehicles in a general sense, then by looking at the individual losses, and calibration factors likely to influence fuel economy.

  20. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia.

    PubMed

    Jourdan, Eric; Boissel, Nicolas; Chevret, Sylvie; Delabesse, Eric; Renneville, Aline; Cornillet, Pascale; Blanchet, Odile; Cayuela, Jean-Michel; Recher, Christian; Raffoux, Emmanuel; Delaunay, Jacques; Pigneux, Arnaud; Bulabois, Claude-Eric; Berthon, Céline; Pautas, Cécile; Vey, Norbert; Lioure, Bruno; Thomas, Xavier; Luquet, Isabelle; Terré, Christine; Guardiola, Philippe; Béné, Marie C; Preudhomme, Claude; Ifrah, Norbert; Dombret, Hervé

    2013-03-21

    Not all patients with core binding factor acute myeloid leukemia (CBF-AML) display a good outcome. Modern risk factors include KIT and/or FLT3 gene mutations and minimal residual disease (MRD) levels, but their respective values have never been prospectively assessed. A total of 198 CBF-AML patients were randomized between a reinforced and a standard induction course, followed by 3 high-dose cytarabine consolidation courses. MRD levels were monitored prospectively. Gene mutations were screened at diagnosis. Despite a more rapid MRD decrease after reinforced induction, induction arm did not influence relapse-free survival (RFS) (64% in both arms; P = .91). Higher WBC, KIT, and/or FLT3-ITD/TKD gene mutations, and a less than 3-log MRD reduction after first consolidation, were associated with a higher specific hazard of relapse, but MRD remained the sole prognostic factor in multivariate analysis. At 36 months, cumulative incidence of relapse and RFS were 22% vs 54% (P < .001) and 73% vs 44% (P < .001) in patients who achieved 3-log MRD reduction vs the others. These results suggest that MRD, rather than gene mutations, should be used for future treatment stratifications in CBF-AML patients. This trial was registered at EudraCT as #2006-005163-26 and at www.clinicaltrials.gov as #NCT 00428558.

  1. What factors influence British medical students' career intentions?

    PubMed

    Ibrahim, Michael; Fanshawe, Angela; Patel, Vanash; Goswami, Karan; Chilvers, Geoffrey; Ting, Michelle; Pilavakis, Yiannis; Rao, Christopher; Athanasiou, Thanos

    2014-12-01

    The aim of this study was to identify factors that influence career choice in UK medical students. Students at seven institutions were invited to rate how important various factors were on influencing their career choices and how interested they were in pursuing different specialties. The influence of interpersonal relationship networks on career choice was also evaluated. 641 responses were collected. 44% (283) were male, 16% (105) were graduates and 41% (263) were final-year students. For Dermatology (p = 0.009), Paediatrics (p = 0.000), Radiology (p = 0.000), Emergency Medicine (p = 0.018) and Cardiothoracic Surgery (p = 0.000), there was a clear correlation between completing a clinical attachment and an interest in pursuing the specialty. Perceived characteristics of the speciality, individually and in clusters were considered important by specific subgroups of students, such as those interested in surgery. These students considered prestige (p = 0.0003), role models (p = 0.014), financial rewards after training (p = 0.0196) and technical challenge (p = 0.0011) as important factors. Demographics such as sex and age played a significant role in career choice. Interpersonal relationship networks do not have a significant influence on career intentions. This study shows that the career intentions of British medical students are influenced by their undergraduate experience and by the weight they place on different specialty-related factors.

  2. Environmental influences: factors influencing a woman's decision to use dietary supplements.

    PubMed

    Conner, Mark; Kirk, Sara F L; Cade, Janet E; Barrett, Jennifer H

    2003-06-01

    Use of dietary supplements by women, particularly those over 40 years of age may be widespread in the United Kingdom. However, from surveillance data, there appears to be a disparity between nutrition and health needs and the rationale for and actual use of dietary supplements by women. This apparent paradox forms the basis for an inverse supplement hypothesis (i.e., supplement use in women appears to be most prevalent among those with least need). Little research has been done to examine the factors underlying the decision to use dietary supplements. Reasons for consuming dietary supplements are often complex, combining social, psychological, knowledge and economic factors. The theory of planned behavior is a widely used model for assessing factors influencing behavioral motivation and action that may be useful for assessing specific diet- and nutrition-related practices. It provided the basis for the development of a questionnaire to explore overall dietary supplement use in a cohort of women in the United Kingdom. The analysis of factors related to beliefs underlying dietary supplement use revealed differences between supplement users and nonusers. Differences included a stronger belief by users than nonusers that taking dietary supplements ensures against possible ill health. Both users and nonusers of supplements also perceived the media (books and magazines) to be a powerful influence on a person's decision to use supplements. These findings highlight the potential of the theory of planned behavior in exploring supplement-taking behavior while throwing light on the factors influencing an individual's motivations to use dietary supplements.

  3. Uncovering Factors Influencing Interpersonal Health Communication

    PubMed Central

    Donné, Lennie; Jansen, Carel; Hoeks, John

    2017-01-01

    Talking to friends, family, or peers about health issues might, among other things, increase knowledge of social norms and feelings of self-efficacy in adopting a healthier lifestyle. We often see interpersonal health communication as an important mediating factor in the effects of health campaigns on health behavior. No research has been done so far, however, on factors that influence whether and how people talk about health issues without being exposed to a health campaign first. In this exploratory study, we interviewed 12 participants about their communication behavior concerning six different health themes, like smoking and exercising. The results suggest that at least four types of interpersonal health communication can be distinguished, each influenced by different factors, like conversational partner and objective of the conversation. Future research should take this diversity of interpersonal health communication into account, and focus on designing health campaigns that aim to trigger dialogue within target populations. PMID:28660238

  4. Hierarchical and coupling model of factors influencing vessel traffic flow.

    PubMed

    Liu, Zhao; Liu, Jingxian; Li, Huanhuan; Li, Zongzhi; Tan, Zhirong; Liu, Ryan Wen; Liu, Yi

    2017-01-01

    Understanding the characteristics of vessel traffic flow is crucial in maintaining navigation safety, efficiency, and overall waterway transportation management. Factors influencing vessel traffic flow possess diverse features such as hierarchy, uncertainty, nonlinearity, complexity, and interdependency. To reveal the impact mechanism of the factors influencing vessel traffic flow, a hierarchical model and a coupling model are proposed in this study based on the interpretative structural modeling method. The hierarchical model explains the hierarchies and relationships of the factors using a graph. The coupling model provides a quantitative method that explores interaction effects of factors using a coupling coefficient. The coupling coefficient is obtained by determining the quantitative indicators of the factors and their weights. Thereafter, the data obtained from Port of Tianjin is used to verify the proposed coupling model. The results show that the hierarchical model of the factors influencing vessel traffic flow can explain the level, structure, and interaction effect of the factors; the coupling model is efficient in analyzing factors influencing traffic volumes. The proposed method can be used for analyzing increases in vessel traffic flow in waterway transportation system.

  5. Factors Influencing College Science Success

    ERIC Educational Resources Information Center

    Tai, Robert H.; Sadler, Philip M.; Mintzes, Joel J.

    2006-01-01

    In this paper, the authors report some of the salient findings of a large-scale, four-year national study, conducted at the Harvard-Smithsonian Center for Astrophysics, entitled "Factors Influencing College Science Success" (FICSS), which surveyed college students who enrolled in first-year biology, chemistry, and physics courses…

  6. Assessment of Factors Influencing Communication in Clinical Pharmacy.

    PubMed

    Yao, Dongning; Jiang, Liang; Huang, Yuankai; Chen, Lei; Wang, Yitao; Xi, Xiaoyu

    2018-01-01

    This study aimed to identify and assess the factors that influence communication quality between clinical pharmacists and patients using a structural equation model based on the predisposing, reinforcing, and enabling constructs in educational/environmental diagnosis and evaluation-policy, regulatory, and organizational constructs in educational and ecological development model to identify the most effective path to increase their communication quality. A survey was conducted at 253 Class-A tertiary hospitals in China from March to December 2016. During on-site observations, verbal communications between clinical pharmacists ( n = 752) and patients were audio recorded, and communication quality was rated by an expert panel on an 8-item Quality of Communication Rating Scale. Clinical pharmacists completed questionnaires that examined the predisposing, enabling, and reinforcing factors that influenced communication quality. Finally, AMOS was employed to examine the relationships between the three factors and communication quality. The results indicated that all three factors positively affected communication quality, with correlation coefficients of .26, .13, and .17, respectively. The most influential predisposing factor was attitude (.77), the most influential enabling factors were self-efficacy (.71) and confidence (.72), and the most influential reinforcing factor was rewards (.74). The findings suggest that pharmacists' attitudes toward, perceived knowledge of, and skill and confidence in communication, and the rewards offered by pharmacy management are the most influential factors that influence communication quality.

  7. Factors influencing the implementation of evidence in Chinese nursing practice.

    PubMed

    Cheng, Lei; Broome, Marion E; Feng, Sheng; Hu, Yan

    2017-12-01

    To explore the influencing factors from staff nurses, nurse managers, nursing directors and a physician involved in nursing evidence implementation in Mainland China. Although the need for evidence-based nursing is well recognised, continuous efforts are needed to strive for closing the gap from evidence to action. Previous studies have explored influencing factors from individual and organisational perspectives in Western countries. However, it remains unclear what the influences (i.e., context and culture) in the developing countries as China. A grounded theory design using in-depth individual interviews was conducted. Interviews with 56 participants from 24 evidence-based nursing implementation projects were conducted in Mainland China. Constant comparative analysis was used to discover the concepts describing the influencing factors during the implementation process. Factors that influenced implementation of evidence-based practice in the Chinese context were identified. These included the leaders of the projects, the nature of the evidence, practising nurses, patients involved in the projects, the system where the projects were implemented, as well as the influence from outside of the system. A variety of factors influencing evidence implementation in Chinese nursing context were identified and further explored from the perspective of different project leaders and culture influence. There is apparently a strong demand for a supportive system, targeted strategies to facilitate various evidence implementations and integrated core elements of evidence-based practice at the point care. The blurred boundaries and complexity of influencing factors call for a systematic and dynamic perspective during implementation. The competitive priorities emphasise the importance of integration between clinical nursing care and evidence-based practice. © 2017 John Wiley & Sons Ltd.

  8. [Factors influencing nurses' organizational citizenship behavior].

    PubMed

    Park, Junhee; Yun, Eunkyung; Han, Sangsook

    2009-08-01

    This study was conducted to identify the factors that influence nurses' organizational citizenship behavior. A cross-sectional design was used, with a convenience sample of 547 nurses from four university hospitals in Seoul and Gyeonggi province. The data were collected through a questionnaire survey done from September 22 to October 10, 2008. The tools used for this study were scales on organizational citizenship behavior (14 items), self-leadership (14 items), empowerment (10 items), organizational commitment (7 items), job satisfaction (8 items) and transformational.transactional leadership (14 items). Cronbach's alpha and factor analysis were examined to test reliability and construct validity of the scale. The data collected were processed using SPSS Window 15.0 Program for actual numbers and percentages, differences in the dependent variable according to general characteristics, and means, standard deviations, correlation coefficients and multiple regression analysis. The factors influencing nurses' organizational citizenship behavior were identified as self-leadership(beta=.247), empowerment (beta=.233), job satisfaction (beta=.209), organizational commitment (beta=.158), and transactional leadership (beta=.142). Five factors explained 42.0% of nurses' organizational citizenship behavior. The results of this study can be used to develop further management strategies for enhancement of nurses' organizational citizenship behavior.

  9. Factors Influencing Title VII Bilingual Program Institutionalization.

    ERIC Educational Resources Information Center

    Lewis, Gerald R.; And Others

    1985-01-01

    This study of the primary restraining and driving forces that influence Title VII bilingual education programs found the external environment, the local community, to be the main factor influencing institutionalization and self-renewal. The internal environment--the local school, and the local school's organization or central office, school board,…

  10. Hierarchical and coupling model of factors influencing vessel traffic flow

    PubMed Central

    Liu, Jingxian; Li, Huanhuan; Li, Zongzhi; Tan, Zhirong; Liu, Ryan Wen; Liu, Yi

    2017-01-01

    Understanding the characteristics of vessel traffic flow is crucial in maintaining navigation safety, efficiency, and overall waterway transportation management. Factors influencing vessel traffic flow possess diverse features such as hierarchy, uncertainty, nonlinearity, complexity, and interdependency. To reveal the impact mechanism of the factors influencing vessel traffic flow, a hierarchical model and a coupling model are proposed in this study based on the interpretative structural modeling method. The hierarchical model explains the hierarchies and relationships of the factors using a graph. The coupling model provides a quantitative method that explores interaction effects of factors using a coupling coefficient. The coupling coefficient is obtained by determining the quantitative indicators of the factors and their weights. Thereafter, the data obtained from Port of Tianjin is used to verify the proposed coupling model. The results show that the hierarchical model of the factors influencing vessel traffic flow can explain the level, structure, and interaction effect of the factors; the coupling model is efficient in analyzing factors influencing traffic volumes. The proposed method can be used for analyzing increases in vessel traffic flow in waterway transportation system. PMID:28414747

  11. Quantitative influence of risk factors on blood glucose level.

    PubMed

    Chen, Songjing; Luo, Senlin; Pan, Limin; Zhang, Tiemei; Han, Longfei; Zhao, Haixiu

    2014-01-01

    The aim of this study is to quantitatively analyze the influence of risk factors on the blood glucose level, and to provide theory basis for understanding the characteristics of blood glucose change and confirming the intervention index for type 2 diabetes. The quantitative method is proposed to analyze the influence of risk factors on blood glucose using back propagation (BP) neural network. Ten risk factors are screened first. Then the cohort is divided into nine groups by gender and age. According to the minimum error principle, nine BP models are trained respectively. The quantitative values of the influence of different risk factors on the blood glucose change can be obtained by sensitivity calculation. The experiment results indicate that weight is the leading cause of blood glucose change (0.2449). The second factors are cholesterol, age and triglyceride. The total ratio of these four factors reaches to 77% of the nine screened risk factors. And the sensitivity sequences can provide judgment method for individual intervention. This method can be applied to risk factors quantitative analysis of other diseases and potentially used for clinical practitioners to identify high risk populations for type 2 diabetes as well as other disease.

  12. Factors influencing healthcare service quality

    PubMed Central

    Mosadeghrad, Ali Mohammad

    2014-01-01

    Background: The main purpose of this study was to identify factors that influence healthcare quality in the Iranian context. Methods: Exploratory in-depth individual and focus group interviews were conducted with 222 healthcare stakeholders including healthcare providers, managers, policy-makers, and payers to identify factors affecting the quality of healthcare services provided in Iranian healthcare organisations. Results: Quality in healthcare is a production of cooperation between the patient and the healthcare provider in a supportive environment. Personal factors of the provider and the patient, and factors pertaining to the healthcare organisation, healthcare system, and the broader environment affect healthcare service quality. Healthcare quality can be improved by supportive visionary leadership, proper planning, education and training, availability of resources, effective management of resources, employees and processes, and collaboration and cooperation among providers. Conclusion: This article contributes to healthcare theory and practice by developing a conceptual framework that provides policy-makers and managers a practical understanding of factors that affect healthcare service quality. PMID:25114946

  13. Soft Factors Influence College Enrollment

    ERIC Educational Resources Information Center

    Fogg, Neeta P.; Harrington, Paul E.

    2010-01-01

    Evidence about the role that "soft factors" like student engagement and school environment play in influencing whether high school students go on to enroll in college is hard to come by. Over the past two years, the Center for Labor Market Studies (CLMS) of Northeastern University, with support from the Nellie Mae Education Foundation…

  14. Factors influencing US medical students' decision to pursue surgery.

    PubMed

    Schmidt, Lauren E; Cooper, Clairice A; Guo, Weidun Alan

    2016-06-01

    Interest and applications to surgery have steadily decreased over recent years in the United States. The goal of this review is to collect the current literature regarding US medical students' experience in surgery and factors influencing their intention to pursue surgery as a career. We hypothesize that multiple factors influence US medical students' career choice in surgery. Six electronic databases (PubMed, SCOPUS, Web of Science, Education Resources Information Center, Embase, and PsycINFO) were searched. The inclusion criteria were studies published after the new century related to factors influencing surgical career choice among US medical students. Factors influencing US medical student surgical career decision-making were recorded. A quality index score was given to each article selected to minimize risk of bias. We identified 38 relevant articles of more than 1000 nonduplicated titles. The factors influencing medical student decision for a surgical career were categorized into five domains: mentorship and role model (n = 12), experience (clerkship n = 9, stereotype n = 4), timing of exposure (n = 9), personal (lifestyle n = 8, gender n = 6, finance n = 3), and others (n = 2). This comprehensive systemic review identifies mentorship, experience in surgery, stereotypes, timing of exposure, and personal factors to be major determinants in medical students' decisions to pursue surgery. These represent areas that can be improved to attract applicants to general surgery residencies. Surgical faculty and residents can have a positive influence on medical students' decisions to pursue surgery as a career. Early introduction to the field of surgery, as well as recruitment strategies during the preclinical and clinical years of medical school can increase students' interest in a surgical career. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi.

    PubMed

    Visco, Carlo; Chiappella, Annalisa; Nassi, Luca; Patti, Caterina; Ferrero, Simone; Barbero, Daniela; Evangelista, Andrea; Spina, Michele; Molinari, Annalia; Rigacci, Luigi; Tani, Monica; Rocco, Alice Di; Pinotti, Graziella; Fabbri, Alberto; Zambello, Renato; Finotto, Silvia; Gotti, Manuel; Carella, Angelo M; Salvi, Flavia; Pileri, Stefano A; Ladetto, Marco; Ciccone, Giovannino; Gaidano, Gianluca; Ruggeri, Marco; Martelli, Maurizio; Vitolo, Umberto

    2017-01-01

    The combination of rituximab, bendamustine, and cytarabine (R-BAC) was highly active in a pilot trial of mantle cell lymphoma, but its use was restricted by high haematological toxicity. We aimed to assess the efficacy and safety of an R-BAC regimen with low-dose cytarabine (RBAC500). In this multicentre, phase 2 trial, we recruited previously untreated patients with an established histological diagnosis of mantle cell lymphoma from 29 Fondazione Italiana Linfomi centres in Italy. Patients had to be older than 65 years and fit according to the comprehensive geriatric assessment, or aged 60-65 years if they were ineligible for high-dose chemotherapy plus autologous stem-cell transplantation and were fit or unfit. All patients received RBAC500 (rituximab 375 mg/m 2 on day 1, bendamustine 70 mg/m 2 on days 2 and 3, and cytarabine 500 mg/m 2 on days 2-4; all administered intravenously) every 4 weeks for up to six cycles. Primary endpoints were the proportion of patients achieving complete response at the end of treatment and toxicity, defined as the occurrence of any of the stop treatment criteria or of any episode of relevant toxicity. All patients who started at least one cycle of RBAC500 were included in the primary and safety analyses. Using efficacy and toxicity as a composite primary endpoint, we considered the final conclusion positive if more than 28 of 57 patients achieve complete response and fewer than 18 of 57 patients report toxicities. This study is registered with EudraCT, number 2011-005739-23, and ClinicalTrials.gov, number NCT01662050, and is completed. Between May 2, 2012, and Feb 25, 2014, we enrolled 57 patients (median age 71 years, IQR 67-75). 54 (95%) patients received at least four RBAC500 cycles (three discontinued because of toxicity), and 38 (67%) completed six cycles. Two (4%) had disease progression (one after the fourth cycle and one after the sixth cycle). All 52 (91%, lower limit of one-sided 95% CI 85%) remaining patients achieved

  16. Factors that influence the childbearing intentions of Canadian men.

    PubMed

    Roberts, E; Metcalfe, A; Jack, M; Tough, S C

    2011-05-01

    The role of men in the childbearing decision process and the factors that influence men's childbearing intentions have been relatively unexplored in the literature. This study aimed to describe the factors that strongly influence the childbearing intentions of men and to describe differences in these factors according to men's age group. A telephone survey (response rate 84%) was conducted with 495 men between the ages of 20 and 45 living in an urban setting who, at the time of contact, did not have biological children. Men were asked about what factors strongly influence their intention to have children. Univariable and multivariable logistic regressions were conducted to determine if these factors were significantly associated with age. Of those sampled, 86% of men reported that at some point in the future they planned to become a parent. The factors that men considered to be most influential in their childbearing intentions were: the need to be financially secure, their partner's interest/desire to have children, their partner's suitability to be a parent and their personal interest/desire to have children. Men who were 35-45 years old had lower odds of stating that financial security (crude OR: 0.32, 95% CI: 0.18-0.54) and partner's interest in having children (crude OR: 0.57, 95% CI: 0.33-0.99) were very influential, but had higher odds of stating that their biological clock (crude OR: 4.37, 95% CI: 1.78-10.76) was very influential in their childbearing intentions than men in the 20-24 year age group. The factors that influence men's intentions about when to become a parent may change with age. Understanding what influences men to have children, and what they understand about reproductive health is important for education, program and policy development.

  17. Factors influencing alcohol safety action project police officers' DWI arrests

    DOT National Transportation Integrated Search

    1974-04-29

    This report summarizes the results of a study to determine the factors influencing ASAP police officers' DWI arrests and the formulation of approaches to minimize the influence of those factors which might tend to constrain the arrest of persons who ...

  18. Marketing Factors Influencing the Overall Satisfaction of Marriage Education Participants.

    ERIC Educational Resources Information Center

    Morris, Michael Lane; Cooper, Catherine; Gross, Kevin H.

    1999-01-01

    Seventy-one married couples attending marriage education workshops were surveyed regarding price, product, place, people, and promotional marketing factors influencing their overall satisfaction as workshop participants. Findings suggest both similar and unique marketing factors influenced husbands' and wives' satisfaction. Recommendations for…

  19. Factors influencing arrests for alcohol-related traffic violations

    DOT National Transportation Integrated Search

    1974-09-01

    This report describes factors that were found to influence police officers' arrests of persons suspected of alcohol-related (A/R) traffic violations, and presents recommendations for treating these factors so that a higher level of enforcement might ...

  20. Factors influencing health information system adoption in American hospitals.

    PubMed

    Wang, Bill B; Wan, Thomas T H; Burke, Darrell E; Bazzoli, Gloria J; Lin, Blossom Y J

    2005-01-01

    To study the number of health information systems (HISs), applicable to administrative, clinical, and executive decision support functionalities, adopted by acute care hospitals and to examine how hospital market, organizational, and financial factors influence HIS adoption. A cross-sectional analysis was performed with 1441 hospitals selected from metropolitan statistical areas in the United States. Multiple data sources were merged. Six hypotheses were empirically tested by multiple regression analysis. HIS adoption was influenced by the hospital market, organizational, and financial factors. Larger, system-affiliated, and for-profit hospitals with more preferred provider organization contracts are more likely to adopt managerial information systems than their counterparts. Operating revenue is positively associated with HIS adoption. The study concludes that hospital organizational and financial factors influence on hospitals' strategic adoption of clinical, administrative, and managerial information systems.

  1. Maturity of hospital information systems: Most important influencing factors.

    PubMed

    Vidal Carvalho, João; Rocha, Álvaro; Abreu, António

    2017-07-01

    Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.

  2. A Review of Factors Influencing Athletes' Food Choices.

    PubMed

    Birkenhead, Karen L; Slater, Gary

    2015-11-01

    Athletes make food choices on a daily basis that can affect both health and performance. A well planned nutrition strategy that includes the careful timing and selection of appropriate foods and fluids helps to maximize training adaptations and, thus, should be an integral part of the athlete's training programme. Factors that motivate food selection include taste, convenience, nutrition knowledge and beliefs. Food choice is also influenced by physiological, social, psychological and economic factors and varies both within and between individuals and populations. This review highlights the multidimensional nature of food choice and the depth of previous research investigating eating behaviours. Despite numerous studies with general populations, little exploration has been carried out with athletes, yet the energy demands of sport typically require individuals to make more frequent and/or appropriate food choices. While factors that are important to general populations also apply to athletes, it seems likely, given the competitive demands of sport, that performance would be an important factor influencing food choice. It is unclear if athletes place the same degree of importance on these factors or how food choice is influenced by involvement in sport. There is a clear need for further research exploring the food choice motives of athletes, preferably in conjunction with research investigating dietary intake to establish if intent translates into practice.

  3. Factors Influencing Teaching Choice in Turkey

    ERIC Educational Resources Information Center

    Kilinc, Ahmet; Watt, Helen M. G.; Richardson, Paul W.

    2012-01-01

    Why choose to become a teacher in Turkey? The authors examined motivations and perceptions among preservice teachers (N = 1577) encompassing early childhood, primary and secondary education. The Factors Influencing Teaching Choice (FIT-Choice) instrument was translated into Turkish and its construct validity and reliability assessed. Altruistic…

  4. Factors Influencing Part-time Faculty Engagement With Online Nursing Programs.

    PubMed

    Reneau, Margaret; Wallace, Cara; Claywell, Lora; Price, Jill; Burdi, Melissa; Trybulski, Joanne

    2018-03-28

    This research investigated factors that influenced the engagement of part-time faculty teaching in online nursing programs with their institutions. Of the 257 part-time faculty surveyed, the most significant factor was being supported in decisions regarding student issues, followed by institutional commitment to quality online education. Compensation was moderately influential; a negative factor was requiring too frequent meetings. Understanding factors that influence the engagement of part-time faculty teaching in online nursing programs can help leaders of online programs attract and retain experienced, highly skilled faculty.

  5. Factors That Influence the Practice of Elective Induction of Labor

    PubMed Central

    Moore, Jennifer; Low, Lisa Kane

    2012-01-01

    Elective induction of labor has been linked to increased rates of prematurity and rising rates of cesarean birth. The purpose of this investigation was to evaluate current trends in induction of labor scholarship focusing on evidence-based factors that influence the practice of elective induction. A key word search was conducted to identify studies on the practice of elective induction of labor. Analysis of the findings included clustering and identification of recurrent themes among the articles with 3 categories being identified. Under each category, the words/phrases were further clustered until a construct could be named. A total of 49 articles met inclusion criteria: 7 patient, 6 maternity care provider, and 4 organization factors emerged. Only 4 of the articles identified were evidence based. Patient factors were divided into preferences/convenience, communication, fear, pressure/influence, trust, external influences, and technology. Provider factors were then divided into practice preferences/convenience, lack of information, financial incentives, fear, patient desire/demand, and technology. Organization factors were divided into lack of enforcement/accountability, hospital culture, scheduling of staff, and market share issues. Currently, there is limited data-based information focused on factors that influence elective induction of labor. Despite patient and provider convenience/preferences being cited in the literature, the evidence does not support this practice. PMID:22843006

  6. Factors which influence necropsy requests: a psychological approach.

    PubMed Central

    Start, R. D.; Hector-Taylor, M. J.; Cotton, D. W.; Startup, M.; Parsons, M. A.; Kennedy, A.

    1992-01-01

    AIMS: To determine which factors influence a clinician's decision to request a necropsy. METHODS: Patient age, confidence in premortem diagnosis, relatives' attitudes, and conditions of necropsy practice were combined factorially (two levels each) in separate medical and surgical questionnaires based on clinical case histories. The interactions between the factors were measured by a repeated measures factorial analysis of variance for each of the two clinical groups. The influence of the clinician's interest in necropsies on these interactions was also examined by a similar method. RESULTS: Necropsies were more likely to be requested on young patients, when diagnostic confidence was low, and when relatives' attitudes were favourable. Conditions of necropsy practice did not affect the likelihood of a request and there was no apparent overall difference in necropsy requests between the two groups of clinicians. The "patient age" and "relatives" factors had less influence on the decision of the surgical group to request necropsy. This was attributed to the opportunity to "see for themselves" at operation and was supported by the finding that surgeons were very likely to request necropsies in the absence of surgical intervention. Clinicians from both groups with a high pre-existing interest in the necropsy were consistently more likely to request necropsies. CONCLUSIONS: The "case history" based questionnaires successfully measured the relative influence of multiple factors in relation to the decision of clinicians to request a necropsy. These findings suggest that any attempt to reverse the decline in necropsy rates should focus on changing the clinician's perception of the value of the modern necropsy. PMID:1556237

  7. Factors influencing women's decisions about timing of motherhood.

    PubMed

    Benzies, Karen; Tough, Suzanne; Tofflemire, Karen; Frick, Corine; Faber, Alexandra; Newburn-Cook, Christine

    2006-01-01

    To examine the factors that influence women's decisions about the timing of motherhood from a life span perspective. Qualitative. Large Western Canadian city with a high rate of infants born to women aged 35 years and older. 45 Canadian women aged 20 to 48 years. Independence, a stable relationship, and declining fertility influenced women's decisions about the timing of motherhood. Women integrated child developmental transitions into a projected life plan as they considered the timing of motherhood. Partner readiness and family of origin influences played a lesser role. Delayed childbearing has become more socially acceptable, with subsequent negative connotations associated with younger motherhood. Parental benefits have limited influence on the timing of motherhood. Recognition by nurses of the various and complex factors that influence women's decisions about the timing of motherhood may flag the importance of pregnancy-related counseling for woman across the fertility life span. Policy decision makers must be cognizant of the need for additional high-risk obstetric and neonatal health services when societal norms encourage women to delay childbearing in favor of completing education and establishing a career. (c) 2006, AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses

  8. Factors influencing internal color of cooked meats.

    PubMed

    Suman, Surendranath P; Nair, Mahesh N; Joseph, Poulson; Hunt, Melvin C

    2016-10-01

    This manuscript overviews the pertinent research on internal color of uncured cooked meats, biochemical processes involved in meat cookery, and fundamental mechanisms governing myoglobin thermal stability. Heat-induced denaturation of myoglobin, responsible for the characteristic dull-brown color of cooked meats, is influenced by a multitude of endogenous (i.e., pH, muscle source, species, redox state) and exogenous (i.e., packaging, ingredients, storage) factors. The interactions between these factors critically influence the internal cooked color and can confuse the consumers, who often perceive cooked color to be a reliable indicator for doneness and safety. While certain phenomena in cooked meat color are cosmetic in nature, others can mislead consumers and result in foodborne illnesses. Research in meat color suggests that processing technologies and cooking practices in industry as well as households influence the internal cooked color. Additionally, the guidelines of many international public health and regulatory authorities recommend using meat thermometers to determine safe cooking endpoint temperature and to ensure product safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Factors influencing warfarin control in Australia and Singapore.

    PubMed

    Bernaitis, Nijole; Ching, Chi Keong; Teo, Siew Chong; Chen, Liping; Badrick, Tony; Davey, Andrew K; Crilly, Julia; Anoopkumar-Dukie, Shailendra

    2017-09-01

    Warfarin is widely used for patients with non-valvular atrial fibrillation (NVAF). Variations in warfarin control, as measured by time in therapeutic range (TTR), have been reported across different regions and ethnicities, particularly between Western and Asian countries. However, there is limited data on comparative factors influencing warfarin control in Caucasian and Asian patients. Therefore, the aim of this study was to determine warfarin control and potential factors influencing this in patients with NVAF in Australia and Singapore. Retrospective data was collected for patients receiving warfarin for January to June 2014 in Australia and Singapore. TTR was calculated for individuals with mean patient TTR used for analysis. Possible influential factors on TTR were analysed including age, gender, concurrent co-morbidities, and concurrent medication. The mean TTR was significantly higher in Australia (82%) than Singapore (58%). At both sites, chronic kidney disease significantly lowered this TTR. Further factors influencing control were anaemia and age<60years in Australia, and vascular disease, CHA 2 DS 2 -VASc score of 6, and concurrent platelet inhibitor therapy in Singapore. Warfarin control was significantly higher in Australia compared to Singapore, however chronic kidney disease reduced control at both sites. The different levels of control in these two countries, together with patient factors further reducing control may impact on anticoagulant choice in these countries with better outcomes from warfarin in Australia compared to Singapore. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Factors Influencing Career Aspirations of Primary and Secondary Grade Students.

    ERIC Educational Resources Information Center

    Canale, Joseph R.; Dunlap, Linda L.

    Many studies have examined factors influencing the career aspirations of high school students, but little has been done to explore this issue with primary school students. This study investigated factors that might influence the career aspirations of children across a broad age spectrum. Students (N=150) from grades 2, 5, 8, and 12 completed…

  11. Factors influencing selection of office furniture by corporations and universities

    Treesearch

    R. Bruce Anderson

    1976-01-01

    Evaluation of the factors that influence the selection of office furniture by large corporations and universities shows that quality, appearance, and purchase price have the most important influence on the purchase decision. The intended use of the furniture and the appearance of the furniture were the key factors in the purchase of wooden furniture.

  12. Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head Biomechanics

    PubMed Central

    Hua, Yi; Voorhees, Andrew P.; Sigal, Ian A.

    2018-01-01

    Purpose To model the sensitivity of the optic nerve head (ONH) biomechanical environment to acute variations in IOP, cerebrospinal fluid pressure (CSFP), and central retinal artery blood pressure (BP). Methods We extended a previously published numerical model of the ONH to include 24 factors representing tissue anatomy and mechanical properties, all three pressures, and constraints on the optic nerve (CON). A total of 8340 models were studied to predict factor influences on 98 responses in a two-step process: a fractional factorial screening analysis to identify the 16 most influential factors, followed by a response surface methodology to predict factor effects in detail. Results The six most influential factors were, in order: IOP, CON, moduli of the sclera, lamina cribrosa (LC) and dura, and CSFP. IOP and CSFP affected different aspects of ONH biomechanics. The strongest influence of CSFP, more than twice that of IOP, was on the rotation of the peripapillary sclera. CSFP had similar influence on LC stretch and compression to moduli of sclera and LC. On some ONHs, CSFP caused large retrolamina deformations and subarachnoid expansion. CON had a strong influence on LC displacement. BP overall influence was 633 times smaller than that of IOP. Conclusions Models predict that IOP and CSFP are the top and sixth most influential factors on ONH biomechanics. Different IOP and CSFP effects suggest that translaminar pressure difference may not be a good parameter to predict biomechanics-related glaucomatous neuropathy. CON may drastically affect the responses relating to gross ONH geometry and should be determined experimentally. PMID:29332130

  13. Factors That Influence Technology Integration in the Classroom

    ERIC Educational Resources Information Center

    Montgomery, Maureen C.

    2017-01-01

    Education is one area where the use of technology has had great impact on student learning. The integration of technology in teaching and learning can significantly influence the outcome of education in the classroom. However, there are a myriad of factors that influence technology integration in the classroom. The purpose of this study was to…

  14. Factors influencing the, selection of state office furniture

    Treesearch

    R. Bruce Anderson; R. Bruce Anderson

    1973-01-01

    Evaluation of the factors influencing the selection of office furniture by nine state governments shows that quality and purchase price have the most important influence on the purchase decision. The intended use of the furniture and the purchasing regulations of the states were key f8CbrS in the use of wood furniture.

  15. Relative importance of natural and anthropogenic factors influencing karst rocky desertification

    NASA Astrophysics Data System (ADS)

    Xu, Erqi; Zhang, Hongqi

    2017-04-01

    As the most severe ecological issue in southwest China, karst rocky desertification (KRD) has both threatened and constrained regional sustainable development. Comprehensively understanding the relationship between the evolution of KRD and relevant driving data would provide more information to combat KRD in such complex karst environments. Past studies have been limited in quantifying the relative importance of driving factors influencing fine-scale KRD evolution, and have also lacked insight into their interactive impacts. To address these issues, we have used geographical information system techniques and a geographical detector model to explore the spatial consistency of driving factors and their interactions in relation to the evolution of KRD. Changshun County in China was selected as a representative area for the study. Nine relevant driving factors, including both natural and anthropogenic factors, were studied in regard to their relationships with KRD transformation between 2000 and 2010. Our results demonstrate the relative importance of driving data in influencing the improvement and deterioration of KRD. Lithology, soil type and road influence are identified as the leading factors. Interestingly, to our study at least, there is no significant difference between the impacts of natural and anthropogenic factors influencing KRD improvement, and even natural factors have a higher impact on KRD deterioration. Factors were found to enhance the influence of each other for KRD transformation. In particular, the results show a non-linearly enhanced effect between driving factors, which significantly aggravates KRD. New information found in our study helps to effectively control and restore areas afflicted by KRD.

  16. Factors that influence women's health in Tanzania.

    PubMed

    Lugina, H I

    1994-01-01

    A descriptive account of factors that influence women's health in Tanzania is given. The social and cultural processes that enhance or undermine women's health are emphasized. Recommendations for changes to improve women's health are made.

  17. Psychosocial factors for influencing healthy aging in adults in Korea.

    PubMed

    Han, KyungHun; Lee, YunJung; Gu, JaSung; Oh, Hee; Han, JongHee; Kim, KwuyBun

    2015-03-07

    Healthy aging includes physical, psychological, social, and spiritual well-being in later years. The purpose of this study is to identify the psychosocial factors influencing healthy aging and examining their socio-demographic characteristics. Perceived health status, depression, self-esteem, self-achievement, ego-integrity, participation in leisure activities, and loneliness were identified as influential factors in healthy aging. 171 Korean adults aged between 45 and 77 years-old participated in the study. Self-reporting questionnaires were used, followed by descriptive statistics and multiple regressions as inferential statistical analyses. There were significant differences between participants' general characteristics: age, education, religion, housing, hobby, and economic status. The factors related to healthy aging had positive correlation with perceived health status, self-esteem, self-achievements, and leisure activities, and negative correlation with depression and loneliness. The factors influencing healthy aging were depression, leisure activities, perceived health status, ego integrity, and self-achievements. These factors were able to explain 51.9%. According to the results, depression is the factor with the greatest influence on healthy aging. Perceived health status, ego integrity, self-achievement, self-esteem, participation of leisure activities were also influential on healthy aging as beneficial factors.

  18. A brief review of salient factors influencing adult eating behaviour.

    PubMed

    Emilien, Christine; Hollis, James H

    2017-12-01

    A better understanding of the factors that influence eating behaviour is of importance as our food choices are associated with the risk of developing chronic diseases such as obesity, CVD, type 2 diabetes or some forms of cancer. In addition, accumulating evidence suggests that the industrial food production system is a major contributor to greenhouse gas emission and may be unsustainable. Therefore, our food choices may also contribute to climate change. By identifying the factors that influence eating behaviour new interventions may be developed, at the individual or population level, to modify eating behaviour and contribute to society's health and environmental goals. Research indicates that eating behaviour is dictated by a complex interaction between physiology, environment, psychology, culture, socio-economics and genetics that is not fully understood. While a growing body of research has identified how several single factors influence eating behaviour, a better understanding of how these factors interact is required to facilitate the developing new models of eating behaviour. Due to the diversity of influences on eating behaviour this would probably necessitate a greater focus on multi-disciplinary research. In the present review, the influence of several salient physiological and environmental factors (largely related to food characteristics) on meal initiation, satiation (meal size) and satiety (inter-meal interval) are briefly discussed. Due to the large literature this review is not exhaustive but illustrates the complexity of eating behaviour. The present review will also highlight several limitations that apply to eating behaviour research.

  19. Alternative Administrative Certification: Socializing Factors Influencing Program Choice

    ERIC Educational Resources Information Center

    Bickmore, Dana L.; Bickmore, Steven T.; Raines, Sarah

    2013-01-01

    This study used an organizational socialization lens to examine factors influencing participants' decision to pursue the principalship and choice to engage in an alternate administration certification program. Through an analysis of participant focus groups and interviews, factors emerged from the codes that were compared with dimensions of…

  20. Factors Influencing the Fatigue Strength of Materials

    NASA Technical Reports Server (NTRS)

    Bollenrath, F

    1941-01-01

    A number of factors are considered which influence the static and fatigue strength of materials under practical operating conditions as contrasted with the relations obtaining under conditions of the usual testing procedure. Such factors are interruptions in operation, periodically fluctuating stress limits and mean stresses with periodic succession of several groups and stress states, statistical changes and succession of stress limits and mean stresses, frictional corrosion at junctures, and notch effects.

  1. How modifiable factors influence parental decision-making about organ donation.

    PubMed

    Luberda, Kamila; Cleaver, Karen

    2017-11-07

    A global shortage of organs from children and adults available for transplantation is compounded by the failure of next of kin to consent for organs to be donated after death. Non-modifiable and modifiable factors influence decision-making in this area. Modifiable factors are of interest when examining families' decision-making about the donation of organs from their deceased child. A scoping review was undertaken to determine how modifiable factors influence parental decision-making about organ donation. Thematic analysis identified two themes: interactions with healthcare professionals and pre-disposition to organ donation. Satisfaction with experiences of hospital care, the information provided and the way it was communicated, as well as interactions pertaining to emotional support were all found to be modifiable factors that influenced decision making. Likewise, a predisposition to organ donation and knowing the deceased's wishes were associated with the consent decision. Nurses working in critical care environments need to be able to support parents during this difficult time. This article aims to raise awareness of modifiable factors that influence parental decision-making, highlighting their relevance for children's nursing practice. ©2017 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  2. Factors influencing laser cutting of wood

    Treesearch

    V.G. Barnekov; C.W. McMillin; H.A. Huber

    1986-01-01

    Factors influencing the ability of lasers to cut wood may be generally classified into these three areas: 1) characteristics of the laser beam; 2) equipment and processing variables; and 3) properties of the workpiece. Effects of beam power, mode, polarization, and stability are discussed as are aspects of optics, location of focal point, feed speed, gas-jet assist...

  3. Review on Factors Influencing Physician Guideline Adherence in Cardiology.

    PubMed

    Hoorn, C J G M; Crijns, H J G M; Dierick-van Daele, A T M; Dekker, L R C

    2018-04-09

    Cardiovascular disease is the most common cause of death in Western countries. Physician adherence to guidelines is often suboptimal, resulting in impaired patient outcome and prognosis. Multiple studies have been conducted to evaluate patterns and the influencing factors of patient adherence, but little is known about factors influencing physician guideline adherence. This review aims to identify factors influencing physician guideline adherence relevant to cardiology and to provide insights and suggestions for future improvement. Physician adherence was measured as adherence to standard local medical practice and applicable guidelines. Female gender and older age had a negative effect on physician guideline adherence. In addition, independent of the type of heart disease, physicians without cardiologic specialization were linked to physician noncompliance. Also, guideline adherence in primary care centers was at a lower level compared to secondary or tertiary care centers. The importance of guideline adherence increases as patients age, and complex diseases and comorbidity arise. Appropriate resources and interventions, taking important factors for nonadherence in account, are necessary to improve guideline adoption and adherence in every level of the chain. This in turn should improve patient outcome.

  4. Librarians' Perspectives on the Factors Influencing Research Data Management Programs

    ERIC Educational Resources Information Center

    Faniel, Ixchel M.; Connaway, Lynn Silipigni

    2018-01-01

    This qualitative research study examines librarians' research data management (RDM) experiences, specifically the factors that influence their ability to support researchers' needs. Findings from interviews with 36 academic library professionals in the United States identify 5 factors of influence: (1) technical resources; (2) human resources; (3)…

  5. Factors influencing societal response of nanotechnology: an expert stakeholder analysis

    NASA Astrophysics Data System (ADS)

    Gupta, Nidhi; Fischer, Arnout R. H.; van der Lans, Ivo A.; Frewer, Lynn J.

    2012-05-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured interviews with experts on nanotechnology from North West Europe were conducted using repertory grid methodology in conjunction with generalized Procrustes analysis to examine the psychological constructs underlying societal uptake of 15 key applications of nanotechnology drawn from different areas (e.g. medicine, agriculture and environment, chemical, food, military, sports, and cosmetics). Based on expert judgement, the main factors influencing societal response to different applications of nanotechnology will be the extent to which applications are perceived to be beneficial, useful, and necessary, and how 'real' and physically close to the end-user these applications are perceived to be by the public.

  6. [Influencing factors in preparation of brucine liposomes by ammonium sulfate transmembrane gradients].

    PubMed

    Wang, Wei; Chen, Jun; Cai, Bao-Chang; Fang, Yun

    2008-09-01

    To study the influencing factors in preparation of brucine liposomes by ammonium sulfate transmembrane gradients. The brucine liposomes were separated by Sephadex G-50, and the influence of various factors on the entrapment efficiencies were investigated. The entrapment efficiency was enhanced by increased ammonium sulfate concentration, ethanol volume and PC concentration. Burcine liposomes prepared by ammonium sulfate transmembrance gradients can get a high entrapment efficiency, the main influencing factors were ammonium sulfate concentration, ethanol volume and PC concentration.

  7. Factors influencing return to work after illness in France.

    PubMed

    Pélissier, C; Fontana, L; Chauvin, F

    2014-01-01

    Few studies have been published about the factors influencing return to work after sickness absence. To identify medical and occupational factors influencing the type of fitness certificate given by occupational physicians before employees return to work after sickness absence. A cross-sectional study was undertaken over 3 months in several health services in France. Workers undergoing a medical examination before returning to work after a period of sickness absence of at least 3 weeks were included. Medical and occupational factors were collected using a questionnaire. The relationship between different factors and certification of fitness was assessed by univariate and multivariate analyses. Among the 402 workers included, 64% were considered fit to return to work. Being older, strenuous work, prolonged sick leave and fear of returning to work appeared to be negative factors influencing the return to a previous job. In contrast, having an education level higher than secondary school, being satisfied at work, perception of very good health and benefitting from satisfactory professional relationships appeared to favour return to work. We developed a predictive score of not being fit to return to work after illness. Our study highlighted the relationship between medical and occupational factors with problems returning to work. The predictive score may be used by occupational physicians as a screening tool to identify those who are likely to have difficulties returning to work after illness, so that their working conditions can be modified to take this into consideration.

  8. Stakeholder Perceptions of Governance: Factors Influencing Presidential Perceptions of Board Effectiveness

    ERIC Educational Resources Information Center

    Proper, Eve; Willmer, Wesley K.; Hartley, Harold V., III; Caboni, Timothy C.

    2009-01-01

    This article examines the factors that influence presidents' perceptions of board effectiveness in relation to their boards' fundraising role. Data from a survey of small college presidents are used to see what factors influence each of four areas of satisfaction: deciding policy, making financial contributions, referring donor prospects and…

  9. Factors influencing the food choices of Irish children and adolescents: a qualitative investigation.

    PubMed

    Fitzgerald, Amanda; Heary, Caroline; Nixon, Elizabeth; Kelly, Colette

    2010-09-01

    Food choices established during childhood and adolescence tend to persist into adulthood with consequences for long-term health. Yet, to date, relatively little research has examined factors that influence the food choices of children and adolescents from their perspectives. In this article, previous research is extended by examining developmental differences between children's and adolescents' perceptions of factors influencing their food choices. Focus group discussions were conducted with 29 young people from three age groups (9-10, 13-14 and 16-18 years). An inductive thematic analysis identified three key factors as influencing food choices. These factors included intra-individual factors: the link between food preferences and awareness of healthy eating; intra-familial factors: the role of the home food environment; and extra-familial factors: eating away from the home. Findings indicate that there were developmental differences between children's and adolescents' perceptions of factors influencing food choice. Among adolescents, parental control began to diminish and adolescents exercised increased autonomy over their food choices compared with children. To develop effective nutrition interventions, it is important to gather child and adolescent input regarding factors perceived as influencing their food choices.

  10. Intrinsic factors influencing help-seeking behaviour in an acute stroke situation.

    PubMed

    Zock, Elles; Kerkhoff, Henk; Kleyweg, Ruud Peter; van de Beek, Diederik

    2016-09-01

    The proportion of stroke patients eligible for intravenous or intra-arterial treatment is still limited because many patients do not seek medical help immediately after stroke onset. The aim of our study was to explore which intrinsic factors and considerations influence help-seeking behaviour of relatively healthy participants, confronted with stroke situations. Semi-structured interviews were conducted with 25 non-stroke participants aged 50 years or older. We presented 5 clinical stroke situations as if experienced by the participants themselves. Recognition and interpretation of symptoms were evaluated and various factors influencing help-seeking behaviour were explored in-depth. We used the thematic synthesis method for data analysis. Five themes influencing help-seeking behaviour in a stroke situation were identified: influence of knowledge, views about seriousness, ideas about illness and health, attitudes towards others and beliefs about the emergency medical system. A correct recognition of stroke symptoms or a correct interpretation of the stroke situations did not automatically result in seeking medical help. Interestingly, similar factors could lead to different types of actions between participants. Many intrinsic, as well as social and environmental factors are of influence on help-seeking behaviour in an acute stroke situation. All these factors seem to play a complex role in help-seeking behaviour with considerable inter-individual variations. Accomplishing more patients eligible for acute stroke treatment, future research should focus on better understanding of all factors at various levels grounded in a theory of help-seeking behaviour.

  11. From Hospital to Nursing Facility: Factors Influencing Decisions

    ERIC Educational Resources Information Center

    Mason, Susan E.; Auerbach, Charles; LaPorte, Heidi Heft

    2009-01-01

    This study addresses the factors influencing decisions to send medicine-surgical (med-surg) patients home or to nursing facilities (NFs). The sample (n = 7,852) was taken from a large, urban, teaching, med-surg unit where discharges were documented and data collected over a two-and-a-half-year period. Using logistical regression, the factors found…

  12. Professional Identity Development in Higher Education: Influencing Factors

    ERIC Educational Resources Information Center

    Barbarà-i-Molinero, Alba; Cascón-Pereira, Rosalía; Hernández-Lara, Ana beatriz

    2017-01-01

    Purpose: In the last few years, the interest on professional identity development (PID) and the factors that influence PID has become central in higher education (HE) literature. However, the knowledge developed in this domain has focussed on a factor at a time and on a degree or discipline, thus being difficult to have a general picture of all…

  13. Computer Self-Efficacy and Factors Influencing E-Learning Effectiveness

    ERIC Educational Resources Information Center

    Chien, Tien-Chen

    2012-01-01

    Purpose: The purpose of this study is to investigate the influences of system and instructor factors on e-learning effectiveness under the interactions of computer self-efficacy. In this study, the factors of the e-learning system are functionality, interaction, and response. The factors of the e-learning instructor are attitude, technical skills,…

  14. Factors Influencing Intrinsic Motivation towards Physical Activity.

    ERIC Educational Resources Information Center

    Rutherford, William J.; And Others

    1992-01-01

    Study examined factors that influenced intrinsic motivation toward physical activity in 60 adult males who completed questionnaires and physical fitness tests. Results showed that performance information given immediately after task performance increased perceived competence and intrinsic motivation levels toward exercise of individuals with…

  15. Factors influencing woodlands of southwestern North Dakota

    Treesearch

    Michele M. Girard; Harold Goetz; Ardell J. Bjugstad

    1987-01-01

    Literature pertaining to woodlands of southwestern North Dakota is reviewed. Woodland species composition and distribution, and factors influencing woodland ecosystems such as climate, logging, fire, and grazing are described. Potential management and improvement techniques using vegetation and livestock manipulation have been suggested.

  16. What Motivational Factors Influence African American Males to Enter a Doctorial Program

    ERIC Educational Resources Information Center

    Humphreys, Phillip

    2010-01-01

    Purpose: The purpose of this study was to determine the motivational factors that influence African American men to enter a doctoral program by identifying the motivational factors that influenced them to enter a doctorial program. The findings were compared to Dr. Gloria J. Hill's dissertation study (2005), "What Motivational Factors Influence…

  17. Factors influencing the intention to watch online video advertising.

    PubMed

    Lee, Joonghwa; Lee, Mira

    2011-10-01

    This study examines the factors influencing consumer intention to watch online video ads, by applying the theory of reasoned action. The attitude toward watching online video ads, the subjective norm, and prior frequency of watching online video ads positively influence the intention to watch online video ads. Further, beliefs held about entertainment and information outcomes from watching online video ads and subjective norm influence attitude toward watching these ads.

  18. Political and economic factors influencing contraceptive uptake.

    PubMed

    Sai, F T

    1993-01-01

    International, national and local level politics influence the uptake of contraception through consensuses, laws, financial and moral support or the creation of an enabling atmosphere. Opposition to contraception generally comes from some churches and groups opposed to particular technologies. Socio-economic factors, particularly education, the health care system and the perceived or actual cost of fertility regulation as compared to benefits expected from children also powerfully influence contraceptive use. For many poor women in developing countries their powerlessness in relation to their male partners is an important obstacle.

  19. Factors Influencing Professional Help-Seeking for Suicidality.

    PubMed

    Han, Jin; Batterham, Philip J; Calear, Alison L; Randall, Rebecca

    2018-05-01

    Evidence suggests that the majority of people with suicidality do not seek help. Little systematic evaluation of factors influencing professional help-seeking has been done. To systematically evaluate the factors that influence professional help-seeking for suicidality. Published quantitative and qualitative studies in Medline and PsycInfo databases were reviewed following PRISMA. In all, 55 relevant studies were identified. Of these, 15 studies examined professional help-seeking intentions for perceived suicidal ideation, among people with or without suicidality; 21 studies examined professional help-seeking behavior among people with suicidality; and 19 studies examined suicidal decedents' health services use. Several potential important barriers were identified including high self-reliance, lack of perceived need for treatment, and stigmatizing attitudes toward suicide, toward mental health issues, and toward seeking professional treatment. The presence of suicidality and mental health issues was found to generally decrease help-seeking intentions for perceived suicidal ideation while facilitating actual service use. Social support and informal support from family and friends also played an important role in professional help-seeking. Although the majority of the included studies were of sound quality, some of the factors identified in the review were assessed in relatively few studies, and most of the included studies were conducted in industrialized countries. Further quantitative and qualitative studies examining the potential important factors in broader community samples, especially in developing countries, are needed.

  20. Factors influencing acceptance of technology for aging in place: a systematic review.

    PubMed

    Peek, Sebastiaan T M; Wouters, Eveline J M; van Hoof, Joost; Luijkx, Katrien G; Boeije, Hennie R; Vrijhoef, Hubertus J M

    2014-04-01

    To provide an overview of factors influencing the acceptance of electronic technologies that support aging in place by community-dwelling older adults. Since technology acceptance factors fluctuate over time, a distinction was made between factors in the pre-implementation stage and factors in the post-implementation stage. A systematic review of mixed studies. Seven major scientific databases (including MEDLINE, Scopus and CINAHL) were searched. Inclusion criteria were as follows: (1) original and peer-reviewed research, (2) qualitative, quantitative or mixed methods research, (3) research in which participants are community-dwelling older adults aged 60 years or older, and (4) research aimed at investigating factors that influence the intention to use or the actual use of electronic technology for aging in place. Three researchers each read the articles and extracted factors. Sixteen out of 2841 articles were included. Most articles investigated acceptance of technology that enhances safety or provides social interaction. The majority of data was based on qualitative research investigating factors in the pre-implementation stage. Acceptance in this stage is influenced by 27 factors, divided into six themes: concerns regarding technology (e.g., high cost, privacy implications and usability factors); expected benefits of technology (e.g., increased safety and perceived usefulness); need for technology (e.g., perceived need and subjective health status); alternatives to technology (e.g., help by family or spouse), social influence (e.g., influence of family, friends and professional caregivers); and characteristics of older adults (e.g., desire to age in place). When comparing these results to qualitative results on post-implementation acceptance, our analysis showed that some factors are persistent while new factors also emerge. Quantitative results showed that a small number of variables have a significant influence in the pre-implementation stage. Fourteen out of

  1. Factors in Client–Clinician Interaction That Influence Hearing Aid Adoption

    PubMed Central

    Jennings, Mary Beth; Shaw, Lynn; Meston, Christine N.; Cheesman, Margaret F.

    2011-01-01

    The influence of client–clinician interactions has not been emphasized in hearing health care, despite the extensive evidence of the impact of the provider–patient interaction on health outcomes. The purpose of this study was to identify factors in the client–clinician interaction that may influence hearing aid adoption. Thirteen adults who had received a hearing aid recommendation within the previous 3 months and 10 audiologists participated in a study to generate, sort, and rate the importance of factors in client–clinician interaction that may influence the hearing aid purchase decision. A concept mapping approach was used to define meaningful clusters of factors. Quantitative analysis and qualitative interpretation of the statements resulted in eight concepts. The concepts in order of their importance are (a) Ensuring client comfort, (b) Understanding and meeting client needs, (c) Client-centered traits and actions, (d) Acknowledging client as an individual, (e) Imposing undue pressure and discomfort, (f) Conveying device information by clinician, (g) Supporting choices and shared decision making, and (h) Factors in client readiness. Two overarching themes of client-centered interaction and client empowerment were identified. Results highlight the influence of the client–clinician interaction in hearing aid adoption and suggest the possibility of improving hearing aid adoption by empowering clients through a client-centered interaction. PMID:22155784

  2. Profiling contextual factors which influence safety in heavy vehicle industries.

    PubMed

    Edwards, Jason R D; Davey, Jeremy; Armstrong, Kerry A

    2014-12-01

    A significant proportion of worker fatalities within Australia result from truck-related incidents. Truck drivers face a number of health and safety concerns. Safety culture, viewed here as the beliefs, attitudes and values shared by an organisation's workers, which interact with their surrounding context to influence behaviour, may provide a valuable lens for exploring safety-related behaviours in heavy vehicle operations. To date no major research has examined safety culture within heavy vehicle industries. As safety culture provides a means to interpret experiences and generate behaviour, safety culture research should be conducted with an awareness of the context surrounding safety. The current research sought to examine previous health and safety research regarding heavy vehicle operations to profile contextual factors which influence health and safety. A review of 104 peer-reviewed papers was conducted. Findings of these papers were then thematically analysed. A number of behaviours and scenarios linked with crashes and non-crash injuries were identified, along with a selection of health outcomes. Contextual factors which were found to influence these outcomes were explored. These factors were found to originate from government departments, transport organisations, customers and the road and work environment. The identified factors may provide points of interaction, whereby culture may influence health and safety outcomes. Copyright © 2014. Published by Elsevier Ltd.

  3. JS-K, an arylating nitric oxide (NO) donor, has synergistic anti-leukemic activity with cytarabine (ARA-C).

    PubMed

    Shami, Paul J; Maciag, Anna E; Eddington, Jordan K; Udupi, Vidya; Kosak, Ken M; Saavedra, Joseph E; Keefer, Larry K

    2009-11-01

    We have designed prodrugs that release nitric oxide (NO) on metabolism by glutathione S-transferases (GST). This design exploits the upregulation of GST in acute myeloid leukemia (AML) cells. O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-leukemic activity. HL-60 myeloid leukemia cells were used for in vitro studies of the combination of JS-K with daunorubicin (DAUNO), cytarabine (ARA-C) or etoposide (ETOP) using the median effect method to determine synergistic, antagonistic, or additive effects. Combinations of JS-K added simultaneously, 2h before or 2h after the other compounds were used. JS-K and DAUNO were antagonistic in all three drug sequences. JS-K and ETOP were also antagonistic but to a lesser degree. JS-K and ARA-C showed strong synergy. The combination index at the 50% fraction affected was 0.37+/-0.23, 0.24+/-0.27, and 0.15+/-0.11 for simultaneous, JS-K first and ARA-C first additions, respectively. JS-K by itself induced DNA strand breaks at relatively high concentrations. However, at submicromolar concentrations, it significantly augmented ARA-C-induced DNA strand breaks. NMR spectroscopy revealed no evidence of chemical interaction between JS-K and the other chemotherapeutic agents. We conclude that ARA-C and JS-K have synergistic anti-leukemic activity and warrant further exploration in combination.

  4. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia.

    PubMed

    Schneider, Constanze; Oellerich, Thomas; Baldauf, Hanna-Mari; Schwarz, Sarah-Marie; Thomas, Dominique; Flick, Robert; Bohnenberger, Hanibal; Kaderali, Lars; Stegmann, Lena; Cremer, Anjali; Martin, Margarethe; Lohmeyer, Julian; Michaelis, Martin; Hornung, Veit; Schliemann, Christoph; Berdel, Wolfgang E; Hartmann, Wolfgang; Wardelmann, Eva; Comoglio, Federico; Hansmann, Martin-Leo; Yakunin, Alexander F; Geisslinger, Gerd; Ströbel, Philipp; Ferreirós, Nerea; Serve, Hubert; Keppler, Oliver T; Cinatl, Jindrich

    2017-02-01

    The nucleoside analog cytarabine (Ara-C) is an essential component of primary and salvage chemotherapy regimens for acute myeloid leukemia (AML). After cellular uptake, Ara-C is converted into its therapeutically active triphosphate metabolite, Ara-CTP, which exerts antileukemic effects, primarily by inhibiting DNA synthesis in proliferating cells. Currently, a substantial fraction of patients with AML fail to respond effectively to Ara-C therapy, and reliable biomarkers for predicting the therapeutic response to Ara-C are lacking. SAMHD1 is a deoxynucleoside triphosphate (dNTP) triphosphohydrolase that cleaves physiological dNTPs into deoxyribonucleosides and inorganic triphosphate. Although it has been postulated that SAMHD1 sensitizes cancer cells to nucleoside-analog derivatives through the depletion of competing dNTPs, we show here that SAMHD1 reduces Ara-C cytotoxicity in AML cells. Mechanistically, dGTP-activated SAMHD1 hydrolyzes Ara-CTP, which results in a drastic reduction of Ara-CTP in leukemic cells. Loss of SAMHD1 activity-through genetic depletion, mutational inactivation of its triphosphohydrolase activity or proteasomal degradation using specialized, virus-like particles-potentiates the cytotoxicity of Ara-C in AML cells. In mouse models of retroviral AML transplantation, as well as in retrospective analyses of adult patients with AML, the response to Ara-C-containing therapy was inversely correlated with SAMHD1 expression. These results identify SAMHD1 as a potential biomarker for the stratification of patients with AML who might best respond to Ara-C-based therapy and as a target for treating Ara-C-refractory AML.

  5. Analysis of factors influencing organic fruit and vegetable purchasing in Istanbul, Turkey.

    PubMed

    Oraman, Yasemin; Unakitan, Gökhan

    2010-01-01

    This article examines the influences on the purchasing decisions of fruit and vegetable consumers and presents findings from a survey conducted with 385 respondents living in urban areas in Istanbul, Turkey. It uses a binary logistic model to estimate factor effects in organic fruit and vegetable purchasing in Turkey. The results indicate that concern for human health and safety is a key factor that influences consumer preferences for organic food. Findings will help organic product suppliers understand the key factors influencing consumer purchasing and consumption behaviors.

  6. Pakistani medical students' specialty preference and the influencing factors.

    PubMed

    Rehman, Anis; Rehman, Tariq; Shaikh, Muhammad Ateeb; Yasmin, Haleema; Asif, Ammara; Kafil, Hina

    2011-07-01

    To elucidate the specialty preferences of Pakistani medical students and the factors which influence medical students to make the decision regarding which specialty to pursue. Both basic sciences and clinical students from four medical colleges of Pakistan, i.e., Dow Medical College, Sindh Medical College, Liaquat National Medical College and Muhammad Medical College, were included in the cross-sectional survey during the period of July 2008 to Jan' 2009. After ethical acceptance, data was collected using convenient sampling technique. The questionnaire covered the following demographic details: 13 common specialties and 15 influencing factors. Questionnaires included in the analysis were 771. Most students gave preference to surgery and its associated sub-specialties (50.3%) followed by internal medicine (26.8%), paediatrics (23.2%), dermatology (16.7%), gynaecology and obstetrics (16.7%), psychiatry (13.1%), radiology (10.8%), ENT (8.8%), anaesthesiology (8.7%), administrative medicine (8.6%), orthopaedics (8.2%), ophthalmology (7.5%), and laboratory medicine (6.1%). The highly considered factors (regarding specialties) chosen by 70% of the medical students were: applicable to respective personalities of the individuals, prestige and respect, international opportunities, and time commitment. Surgical-skills, job availability, financial rating, academic performance, and a role model were moderately influencing factors. Hospital environment, parents, general practice, peer-pressure and personal health were the least influential. This trend suggests competition in surgery and its sub-specialties along with internal medicine, paediatrics, dermatology, gynaecology and obstetrics. Specialty suited to personality, time commitment, prestige/respect and international opportunity, influenced more than 70% of the students.

  7. Factors influencing training transfer in nursing profession: a qualitative study.

    PubMed

    Ma, Fang; Bai, Yangjing; Bai, Yangjuan; Ma, Weiguang; Yang, Xiangyu; Li, Jiping

    2018-03-20

    There is a growing recognition that training is not translated into performance and the 'transfer problem' exists in organization training today. Although factors contributing to training transfer have been identified in business and industry, the factors influencing training transfer in nursing profession remain less clear. A qualitative descriptive study was undertaken in two tertiary referral hospitals in China from February 2013 to September 2013. Purposeful sampling of 24 nursing staffs were interviewed about the factors influencing training transfer. Seven themes evolved from the analysis, categorized in 4 main domains, which described the factors influencing training transfer in nursing profession in trainee characteristics, training design, work environment and profession domain. The trainee characteristics domain included attitude and ability. The training design domain included training content and instruction method. The work environment domain included supports as facilitators and opposition as hindrance. The theme pertaining to the profession domain was professional development. Health care managers need to understand the factors influencing training transfer for maximizing the benefits of training. The right beliefs and values about training, the rigorous employee selection for training, the relevance of training content, training instructions facilitating learning and transfer, supports from peer, supervisors and the organization, organizational culture such as change, sharing, learning and support, and professional development are key to successful training transfer. Furthermore, managers should be aware of the opposition from co-workers and find ways to prevent it.

  8. Factors influencing antibiotic prescribing in long-term care facilities: a qualitative in-depth study.

    PubMed

    van Buul, Laura W; van der Steen, Jenny T; Doncker, Sarah M M M; Achterberg, Wilco P; Schellevis, François G; Veenhuizen, Ruth B; Hertogh, Cees M P M

    2014-12-16

    Insight into factors that influence antibiotic prescribing is crucial when developing interventions aimed at a more rational use of antibiotics. We examined factors that influence antibiotic prescribing in long-term care facilities, and present a conceptual model that integrates these factors. Semi-structured qualitative interviews were conducted with physicians (n = 13) and nursing staff (n = 13) in five nursing homes and two residential care homes in the central-west region of the Netherlands. An iterative analysis was applied to interviews with physicians to identify and categorize factors that influence antibiotic prescribing, and to integrate these into a conceptual model. This conceptual model was triangulated with the perspectives of nursing staff. The analysis resulted in the identification of six categories of factors that can influence the antibiotic prescribing decision: the clinical situation, advance care plans, utilization of diagnostic resources, physicians' perceived risks, influence of others, and influence of the environment. Each category comprises several factors that may influence the decision to prescribe or not prescribe antibiotics directly (e.g. pressure of patients' family leading to antibiotic prescribing) or indirectly via influence on other factors (e.g. unfamiliarity with patients resulting in a higher physician perceived risk of non-treatment, in turn resulting in a higher tendency to prescribe antibiotics). Our interview study shows that several non-rational factors may affect antibiotic prescribing decision making in long-term care facilities, suggesting opportunities to reduce inappropriate antibiotic use. We developed a conceptual model that integrates the identified categories of influencing factors and shows the relationships between those categories. This model may be used as a practical tool in long-term care facilities to identify local factors potentially leading to inappropriate prescribing, and to subsequently

  9. Factors that influence women's dispositions toward science

    NASA Astrophysics Data System (ADS)

    Atria, Catherine Graczyk

    Females have been underrepresented in the study of science and science careers for decades although advancements have been made in closing this gender gap, the gap persists particularly in the physical sciences. Variables which influence a woman's desire to pursue and maintain a science course of study and career must be discovered. The United States lags behind other industrialized countries in the fields of science, math, and engineering. Females comprise an estimated half of the population; their potential contributions cannot be ignored or overlooked. This retrospective research study explores the personal experiences of ten women enrolled in science majors, with science related career plans. The goal of this study is to describe the factors that influence the participants' interest in science. The findings, the effect of science coursework, science teachers' personality and manner, other influential educational personnel, role models and mentors, external influences exclusive of school, parental influence, locus of control and positive attitudes toward science confirm what other researchers have found.

  10. Factors influencing post-traumatic stress in Korean forensic science investigators.

    PubMed

    Yoo, Yang-Sook; Cho, Ok-Hee; Cha, Kyeong-Sook; Boo, Yun-Jeong

    2013-09-01

    The aim of this study was to understand factors that influence post-traumatic stress (PTS) in Korean forensic science investigators. A total of 111 forensic science investigators were recruited in Korea. PTS was measured using the tool modified by Choi (2001) from the original developed by Foa, Riggs, Dancu, and Rothbaum (1993) based on DSM-IV. Factors influencing PTS included demographic and job-related characteristics, emotional intelligence, and death anxiety. PTS scores were positively correlated with personality type, fatigue from work, and death anxiety. PTS scores were negatively correlated with length of career as a forensic science investigator and emotional intelligence. The factors that had the greatest influence on PTS were death anxiety, years spent as a forensic science investigator, personality type, emotional intelligence, fatigue, and homicide experience. The explanatory power of these six factors was 44.0%. Therefore, it is necessary to regularly evaluate the mental health of those who are vulnerable to PTS. Based on these results, various interventions could be implemented for promoting overall health of the forensic science investigators. Copyright © 2013. Published by Elsevier B.V.

  11. Factors Potentially Influencing Student Acceptance of Biological Evolution

    NASA Astrophysics Data System (ADS)

    Wiles, Jason R.

    This investigation explored scientific, religious, and otherwise nonscientific factors that may influence student acceptance of biological evolution and related concepts, how students perceived these factors to have influenced their levels of acceptance of evolution and changes therein, and what patterns arose among students' articulations of how their levels of acceptance of evolution may have changed. This exploration also measured the extent to which students' levels of acceptance changed following a treatment designed to address factors identified as potentially affecting student acceptance of evolution. Acceptance of evolution was measured using the MATE instrument (Rutledge and Warden, 1999; Rutledge and Sadler, 2007) among participants enrolled in a secondary-level academic program during the summer prior to their final year of high school and as they transitioned to the post-secondary level. Student acceptance of evolution was measured to be significantly higher than pre-treatment levels both immediately following and slightly over one year after treatment. Qualitative data from informal questionnaires, from formal course evaluations, and from semi-structured interviews of students engaged in secondary level education and former students at various stages of post-secondary education confirmed that the suspected factors were perceived by participants to have influenced their levels of acceptance of evolution. Furthermore, participant reports provided insight regarding the relative effects they perceived these factors to have had on their evolution acceptance levels. Additionally, many participants reported that their science teachers in public schools had avoided, omitted, or denigrated evolution during instruction, and several of these students expressed frustration regarding what they perceived to have been a lack of education of an important scientific principle. Finally, no students expressed feelings of being offended by having been taught about

  12. Factors influencing worker use of personal protective eyewear.

    PubMed

    Lombardi, David A; Verma, Santosh K; Brennan, Melanye J; Perry, Melissa J

    2009-07-01

    To identify and describe the array of factors that influence a workers' decision to wear personal protective eyewear (PPE) and the barriers that exist in preventing their use. A series of focus groups enrolled workers and supervisors primarily from manufacturing, construction, or service/retail industries that had potential exposure to eye injury hazards in their job tasks. Focus group sessions were facilitated to collect qualitative and quantitative data in two categories, "sought information" and "emergent themes", related to the factors influencing use of PPE. We conducted a series of 7 groups with 51 participants, 36 (71%) males and 15 (29%) females ranging in age from 19 to 64 years old, from a variety of occupations including construction (24%), production (22%), installation, repair and maintenance (14%), and healthcare (10%). Most were highly experienced in their occupation (>10 years); males (86%) and females (53%), and had received some safety training in the past (82%). The majority of workers in this study were required to wear PPE on their worksite (78%), however only 55% had a dedicated safety officer. A conceptual model that summarizes the "sought information" and "emergent themes" is presented that depicts the decision making process for the factors influencing use of PPE and consists of three primary branches; perceptions of hazards and risks, "barriers" to PPE usage, and enforcement and reinforcement. Lack of comfort/fit, and fogging and scratching of the eyewear were suggested as the most important barriers to PPE usage. Younger age and lack of safety training were other important factors affecting use of PPE. Several potentially modifiable factors identified would lead to an increase in workers' PPE use and encourage supervisors to provide ongoing positive feedback on the continuous use of PPE by workers at risk for an eye injury.

  13. Why neurology? Factors which influence career choice in neurology.

    PubMed

    Albert, Dara V; Hoyle, Chad; Yin, Han; McCoyd, Matthew; Lukas, Rimas V

    2016-01-01

    To evaluate the factors which influence the decision to pursue a career in neurology. An anonymous survey was developed using a Likert scale to rate responses. The survey was sent to adult and child neurology faculty, residents and fellows, as well as medical students applying for neurology. Descriptive statistics were used to analyse the factors of influence. Respondents were subsequently categorized into pre-neurology trainees, neurology trainees, child neurologists and adult neurologists, and differences between the groups were analysed using Pearson's chi-square test. One hundred and thirty-three anonymous responses were received. The respondents were neurologists across all levels of training and practice. Across all respondents, the most common factor of high importance was intellectual content of specialty, challenging diagnostic problems, type of patient encountered and interest in helping people. Responses were similar across the groups; however, the earliest trainees cited interest in helping people as most important, while those in neurology training and beyond cite intellectual content of the specialty as most important. As trainees transition from their earliest levels of clinical experience into working as residents and faculty, there is a shift in the cited important factors. Lifestyle and financial factors seem to be the least motivating across all groups. Encouragement from peers, mentors, faculty and practicing physicians is considered high influences in a smaller number of neurologists. This may present an opportunity for practicing neurologists to make connections with medical students early in their education in an effort to encourage and mentor candidates.

  14. Consumer's Online Shopping Influence Factors and Decision-Making Model

    NASA Astrophysics Data System (ADS)

    Yan, Xiangbin; Dai, Shiliang

    Previous research on online consumer behavior has mostly been confined to the perceived risk which is used to explain those barriers for purchasing online. However, perceived benefit is another important factor which influences consumers’ decision when shopping online. As a result, an integrated consumer online shopping decision-making model is developed which contains three elements—Consumer, Product, and Web Site. This model proposed relative factors which influence the consumers’ intention during the online shopping progress, and divided them into two different dimensions—mentally level and material level. We tested those factors with surveys, from both online volunteers and offline paper surveys with more than 200 samples. With the help of SEM, the experimental results show that the proposed model and method can be used to analyze consumer’s online shopping decision-making process effectively.

  15. [Analysis of influencing factors of snow hyperspectral polarized reflections].

    PubMed

    Sun, Zhong-Qiu; Zhao, Yun-Sheng; Yan, Guo-Qian; Ning, Yan-Ling; Zhong, Gui-Xin

    2010-02-01

    Due to the need of snow monitoring and the impact of the global change on the snow, on the basis of the traditional research on snow, starting from the perspective of multi-angle polarized reflectance, we analyzed the influencing factors of snow from the incidence zenith angles, the detection zenith angles, the detection azimuth angles, polarized angles, the density of snow, the degree of pollution, and the background of the undersurface. It was found that these factors affected the spectral reflectance values of the snow, and the effect of some factors on the polarization hyperspectral reflectance observation is more evident than in the vertical observation. Among these influencing factors, the pollution of snow leads to an obvious change in the snow reflectance spectrum curve, while other factors have little effect on the shape of the snow reflectance spectrum curve and mainly impact the reflection ratio of the snow. Snow reflectance polarization information has not only important theoretical significance, but also wide application prospect, and provides new ideas and methods for the quantitative research on snow using the remote sensing technology.

  16. Factors Influencing Renewable Energy Production & Supply - A Global Analysis

    NASA Astrophysics Data System (ADS)

    Ali, Anika; Saqlawi, Juman Al

    2016-04-01

    Renewable energy is one of the key technologies through which the energy needs of the future can be met in a sustainable and carbon-neutral manner. Increasing the share of renewable energy in the total energy mix of each country is therefore a critical need. While different countries have approached this in different ways, there are some common aspects which influence the pace and effectiveness of renewable energy incorporation. This presentation looks at data and information from 34 selected countries, analyses the patterns, compares the different parameters and identifies the common factors which positively influence renewable energy incorporation. The most successful countries are analysed for their renewable energy performance against their GDP, policy/regulatory initiatives in the field of renewables, landmass, climatic conditions and population to identify the most influencing factors to bring about positive change in renewable energy share.

  17. The Influence Factors and Mechanism of Societal Risk Perception

    NASA Astrophysics Data System (ADS)

    Zheng, Rui; Shi, Kan; Li, Shu

    Risk perception is one of important subjects in management psychology and cognitive psychology. It is of great value in the theory and practice to investigate the societal hazards that the public cares a lot especially in Socio-economic transition period. A survey including 30 hazards and 6 risk attributes was designed and distributed to about 2, 485 residents of 8 districts, Beijing. The major findings are listed as following: Firstly, a scale of societal risk perception was designed and 2 factors were identified (Dread Risk & Unknown Risk). Secondly, structural equation model was used to analyze the influence factors and mechanism of societal risk perception. Risk preference, government support and social justice could influence societal risk perception directly. Government support fully moderated the relationship between government trust and societal risk perception. Societal risk perception influenced life satisfaction, public policy preferences and social development belief.

  18. Factors influencing the flavour of game meat: A review.

    PubMed

    Neethling, J; Hoffman, L C; Muller, M

    2016-03-01

    Flavour is a very important attribute contributing to the sensory quality of meat and meat products. Although the sensory quality of meat includes orthonasal and retronasal aroma, taste, as well as appearance, juiciness and other textural attributes, the focus of this review is primarily on flavour. The influence of species, age, gender, muscle anatomical location, diet, harvesting conditions, ageing of meat, packaging and storage, as well as cooking method on the flavour of game meat are discussed. Very little research is available on the factors influencing the flavour of the meat derived from wild and free-living game species. The aim of this literature review is thus to discuss the key ante- and post-mortem factors that influence the flavour of game meat, with specific focus on wild and free-living South African game species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Factors Influencing Employee Learning in Small Businesses

    ERIC Educational Resources Information Center

    Coetzer, Alan; Perry, Martin

    2008-01-01

    Purpose: The purpose of this research is to identify key factors influencing employee learning from the perspective of owners/managers. Design/methodology/research: Data were gathered from owners/managers in a total of 27 small manufacturing and services firms through interviews and analysed using content analytic procedures. Findings: The…

  20. Exploring Factors That Influence Quality Literature Circles

    ERIC Educational Resources Information Center

    Young, Chase; Mohr, Kathleen A. J.

    2018-01-01

    Research indicates that literature circles are an authentic means for literacy development that students typically enjoy. To better understand the potential value and to add to the research base regarding literature circles, this study, involving 17 fourth graders, explores factors that may influence the quality of literature discussions,…

  1. A Survey of Factors Influencing High School Start Times

    ERIC Educational Resources Information Center

    Wolfson, Amy R.; Carskadon, Mary A.

    2005-01-01

    The present study surveyed high school personnel regarding high school start times, factors influencing school start times, and decision making around school schedules. Surveys were analyzed from 345 secondary schools selected at random from the National Center for Educational Statistics database. Factors affecting reported start times included…

  2. Factors influencing global antiretroviral procurement prices.

    PubMed

    Wirtz, Veronika J; Forsythe, Steven; Valencia-Mendoza, Atanacio; Bautista-Arredondo, Sergio

    2009-11-18

    Antiretroviral medicines (ARVs) are one of the most costly parts of HIV/AIDS treatment. Many countries are struggling to provide universal access to ARVs for all people living with HIV and AIDS. Although substantial price reductions of ARVs have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global ARV prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on ARV procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to ARV programs. An ARV-medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 ARVs, global median prices and price variation were calculated. Linear regression models for each ARV were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Three key factors appear to have an influence on a country's ARV prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan For AIDS Relief. One of the principal mechanisms that can help to lower prices for ARV over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful tool to achieve this.

  3. Factors influencing global antiretroviral procurement prices

    PubMed Central

    2009-01-01

    Background Antiretroviral medicines (ARVs) are one of the most costly parts of HIV/AIDS treatment. Many countries are struggling to provide universal access to ARVs for all people living with HIV and AIDS. Although substantial price reductions of ARVs have occurred, especially between 2002 and 2008, achieving sustainable access for the next several decades remains a major challenge for most low- and middle-income countries. The objectives of the present study were twofold: first, to analyze global ARV prices between 2005 and 2008 and associated factors, particularly procurement methods and key donor policies on ARV procurement efficiency; second, to discuss the options of procurement processes and policies that should be considered when implementing or reforming access to ARV programs. Methods An ARV-medicines price-analysis was carried out using the Global Price Reporting Mechanism from the World Health Organization. For a selection of 12 ARVs, global median prices and price variation were calculated. Linear regression models for each ARV were used to identify factors that were associated with lower procurement prices. Logistic regression models were used to identify the characteristics of those countries which procure below the highest and lowest direct manufactured costs. Results Three key factors appear to have an influence on a country's ARV prices: (a) whether the product is generic or not; (b) the socioeconomic status of the country; (c) whether the country is a member of the Clinton HIV/AIDS Initiative. Factors which did not influence procurement below the highest direct manufactured costs were HIV prevalence, procurement volume, whether the country belongs to the least developed countries or a focus country of the United States President's Emergency Plan For AIDS Relief. Conclusion One of the principal mechanisms that can help to lower prices for ARV over the next several decades is increasing procurement efficiency. Benchmarking prices could be one useful

  4. Influencing factors on the visibility of surface distresses

    NASA Astrophysics Data System (ADS)

    Smęt, Wojciech; Skakuj, Marek

    2018-05-01

    A systematic and future-oriented maintenance management requires quality-assured data regarding the condition of the roadway. An important characteristic for assessing the condition of the road surface are cracks [1]. Experience has proven that the road surface temperature and residual humidity can influence the visibility of cracks. To investigate and quantify these influencing factors in more detail, the Federal Ministry of Transport and Digital Infrastructure has implemented a comprehensive research project [2], during which several measurement campaigns were carried out at different seasons and at different temperatures and humidity degrees of the road surface. The visibility of the cracks was assessed using the German approach ZTV ZEB-StB [3]. After evaluating the cracks, the data was synchronized and the network allocation of the geo-referenced raw data was realized. The relevant condition performance indicators were calculated subsequently. For each evaluation section of 100 meters length, the mean road surface temperature was calculated and, if available, the type and year of construction of the surface course was determined. The evaluated data was visualized to establish correlations between the data and the influencing factors. For the statistical analysis of the results, a total of six comparative scenarios were defined in which the influencing factors of road surface temperature and residual humidity were assessed. This paper documents the results of the research project. In order to obtain a uniform and comparable picture of the condition of the road surface over the years and thus to be able to observe the aging process of the road surface, the measurement campaigns are to be carried out under defined conditions. The research project included proposals for defining and further specifying the measurement conditions.

  5. Attitudes, norms and controls influencing lifestyle risk factor management in general practice.

    PubMed

    Ampt, Amanda J; Amoroso, Cheryl; Harris, Mark F; McKenzie, Suzanne H; Rose, Vanessa K; Taggart, Jane R

    2009-08-26

    With increasing rates of chronic disease associated with lifestyle behavioural risk factors, there is urgent need for intervention strategies in primary health care. Currently there is a gap in the knowledge of factors that influence the delivery of preventive strategies by General Practitioners (GPs) around interventions for smoking, nutrition, alcohol consumption and physical activity (SNAP). This qualitative study explores the delivery of lifestyle behavioural risk factor screening and management by GPs within a 45-49 year old health check consultation. The aims of this research are to identify the influences affecting GPs' choosing to screen and choosing to manage SNAP lifestyle risk factors, as well as identify influences on screening and management when multiple SNAP factors exist. A total of 29 audio-taped interviews were conducted with 15 GPs and one practice nurse over two stages. Transcripts from the interviews were thematically analysed, and a model of influencing factors on preventive care behaviour was developed using the Theory of Planned Behaviour as a structural framework. GPs felt that assessing smoking status was straightforward, however some found assessing alcohol intake only possible during a formal health check. Diet and physical activity were often inferred from appearance, only being assessed if the patient was overweight. The frequency and thoroughness of assessment were influenced by the GPs' personal interests and perceived congruence with their role, the level of risk to the patient, the capacity of the practice and availability of time. All GPs considered advising and educating patients part of their professional responsibility. However their attempts to motivate patients were influenced by perceptions of their own effectiveness, with smoking causing the most frustration. Active follow-up and referral of patients appeared to depend on the GPs' orientation to preventive care, the patient's motivation, and cost and accessibility of

  6. Motivational factors influencing nurses to undertake postgraduate hospital-based education.

    PubMed

    Kinsella, Danny; Fry, Margaret; Zecchin, Alison

    2018-05-01

    Specialist postgraduate education improves patient health outcomes, and assists in meeting the emerging specialisation of nursing practice. The aim of this study was to investigate the motivational factors that influence nurses' engagement with hospital-based postgraduate education. The research design was descriptive and exploratory, using a survey method. The survey consisted of demographic details, the Participation Reasons Scale (PRS) and open-ended questions. Thirty-four participants (100%) completed the survey. Of the PRS extrinsic and intrinsic factors, Professional Improvement and Development (Factor 1) and Professional Service (Factor 2), both intrinsic factors, ranked the highest. Therefore, this study identified that intrinsic motivation factors influenced engagement with postgraduate specialty programs for early career nurses. These results highlight the importance of intrinsic motivation factors for a nursing workforce and how this can potentially drive behaviour and decision making. A better understanding of motivation factors across a nurse's career could lead to educational strategies that optimise postgraduate program engagement to better support healthcare delivery and a culture of lifelong learning. Copyright © 2018. Published by Elsevier Ltd.

  7. Nurturing Sport Expertise: Factors Influencing the Development of Elite Athlete

    PubMed Central

    Baker, Joseph; Horton, Sean; Robertson-Wilson, Jennifer; Wall, Michael

    2003-01-01

    The development of expertise in sport is the result of successful interaction of biological, psychological, and sociological constraints. This review examines the training and environmental factors that influence the acquisition of sport expertise. Research examining the quality and quantity of training indicate that these two elements are crucial predictors of attainment. In addition, the possession of resources such as parental support and adequate coaching are essential. Social factors such as cultural influences and the relative age effect are also considered as determinants of sport expertise. Although it is evident that environmental factors are essential to the acquisition of high levels of sport development, further research is clearly required. PMID:24616603

  8. Analysis of the influencing factors of global energy interconnection development

    NASA Astrophysics Data System (ADS)

    Zhang, Yi; He, Yongxiu; Ge, Sifan; Liu, Lin

    2018-04-01

    Under the background of building global energy interconnection and achieving green and low-carbon development, this paper grasps a new round of energy restructuring and the trend of energy technology change, based on the present situation of global and China's global energy interconnection development, established the index system of the impact of global energy interconnection development factors. A subjective and objective weight analysis of the factors affecting the development of the global energy interconnection was conducted separately by network level analysis and entropy method, and the weights are summed up by the method of additive integration, which gives the comprehensive weight of the influencing factors and the ranking of their influence.

  9. Factors influencing cancer treatment decision-making by indigenous peoples: a systematic review.

    PubMed

    Tranberg, Rona; Alexander, Susan; Hatcher, Deborah; Mackey, Sandra; Shahid, Shaouli; Holden, Lynda; Kwok, Cannas

    2016-02-01

    We aim to systematically review studies that identify factors influencing cancer treatment decision-making among indigenous peoples. Following the outline suggested by the Preferred Reporting Items for Systematic Review and Meta-analysis, a rigorous systematic review and meta-synthesis were conducted of factors that influence cancer treatment decision-making by indigenous peoples. A total of 733 articles were retrieved from eight databases and a manual search. After screening the titles and abstracts, the full text of 26 articles were critically appraised, resulting in five articles that met inclusion criteria for the review. Because the five articles to be reviewed were qualitative studies, the Critical Appraisal Skills Program toolkit was used to evaluate the methodological quality. A thematic synthesis was employed to identify common themes across the studies. Multiple socio-economic and cultural factors were identified that all had the potential to influence cancer treatment decision-making by indigenous people. These factors were distilled into four themes: spiritual beliefs, cultural influences, communication and existing healthcare systems and structures. Although existing research identified multiple factors influencing decision-making, this review identified that quality studies in this domain are scarce. There is scope for further investigation, both into decision-making factors and into the subsequent design of culturally appropriate programmes and services that meet the needs of indigenous peoples. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Factors Influencing Pursuit of Higher Education: Validating a Questionnaire.

    ERIC Educational Resources Information Center

    Harris, Sandra M.

    This paper explains the process used to validate the construct validity of the Factors Influencing Pursuit of Higher Education Questionnaire. This questionnaire is a literature-based, researcher-developed instrument which gathers information on the factors thought to affect a person's decision to pursue higher education. The questionnaire includes…

  11. Concrete pavement mixture design and analysis (MDA) : factors influencing drying shrinkage.

    DOT National Transportation Integrated Search

    2014-10-01

    This literature review focuses on factors influencing drying shrinkage of concrete. Although the factors are normally interrelated, they : can be categorized into three groups: paste quantity, paste quality, and other factors.

  12. An Analysis of Factors that Influence Enlistment Decisions in the U.S. Army

    DTIC Science & Technology

    1998-03-01

    NAVAL POSTGRADUATE SCHOOL Monterey, California CM THESIS AN ANALYSIS OF FACTORS THAT INFLUENCE ENLISTMENT DECISIONS IN THE U.S. ARMY by Young...TITLE AND SUBTITLE : AN ANALYSIS OF FACTORS THAT INFLUENCE ENLISTMENT DECISIONS IN THE U.S. ARMY 6. AUTHOR(S) Oh, Young Yeol 7...200 words) The purpose of this thesis is to analyze factors that influence decisions to enlist in the U.S. Army. This thesis uses 1997 New Recruit

  13. From shared care to disease management: key-influencing factors

    PubMed Central

    Eijkelberg, Irmgard M.J.G.; Spreeuwenberg, Cor; Mur-Veeman, Ingrid M.; Wolffenbuttel, Bruce H.R.

    2001-01-01

    Abstract Background In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called ‘shared care’ projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Objective Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? Theory The theoretical framework is based on the concept of the learning organisation. Design Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. Results In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skilful way. Conclusion Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed. PMID:16896415

  14. From shared care to disease management: key-influencing factors.

    PubMed

    Eijkelberg, I M; Spreeuwenberg, C; Mur-Veeman, I M; Wolffenbuttel, B H

    2001-01-01

    In order to improve the quality of care of chronically ill patients the traditional boundaries between primary and secondary care are questioned. To demolish these boundaries so-called 'shared care' projects have been initiated in which different ways of substitution of care are applied. When these projects end, disease management may offer a solution to expand the achieved co-operation between primary and secondary care. Answering the question: What key factors influence the development and implementation of shared care projects from a management perspective and how are they linked? The theoretical framework is based on the concept of the learning organisation. Reference point is a multiple case study that finally becomes a single case study. Data are collected by means of triangulation. The studied cases concern two interrelated Dutch shared care projects for type 2 diabetic patients, that in the end proceed as one disease management project. In these cases the predominant key-influencing factors appear to be the project management, commitment and local context, respectively. The factor project management directly links the latter two, albeit managing both appear prerequisites to its success. In practice this implies managing the factors' interdependency by the application of change strategies and tactics in a committed and skillful way. Project management, as the most important and active key factor, is advised to cope with the interrelationships of the influencing factors in a gradually more fundamental way by using strategies and tactics that enable learning processes. Then small-scale shared care projects may change into a disease management network at a large scale, which may yield the future blueprint to proceed.

  15. Critical factors and paths influencing construction workers' safety risk tolerances.

    PubMed

    Wang, Jiayuan; Zou, Patrick X W; Li, Penny P

    2016-08-01

    While workers' safety risk tolerances have been regarded as a main reason for their unsafe behaviors, little is known about why different people have different risk tolerances even when confronting the same situation. The aim of this research is to identify the critical factors and paths that influence workers' safety risk tolerance and to explore how they contribute to accident causal model from a system thinking perceptive. A number of methods were carried out to analyze the data collected through interviews and questionnaire surveys. In the first and second steps of the research, factor identification, factor ranking and factor analysis were carried out, and the results show that workers' safety risk tolerance can be influenced by four groups of factors, namely: (1) personal subjective perception; (2) work knowledge and experiences; (3) work characteristics; and (4) safety management. In the third step of the research, hypothetical influencing path model was developed and tested by using structural equation modeling (SEM). It is found that the effects of external factors (safety management and work characteristics) on risk tolerance are larger than that of internal factors (personal subjective perception and work knowledge & experiences). Specifically, safety management contributes the most to workers' safety risk tolerance through its direct effect and indirect effect; while personal subjective perception comes the second and can act as an intermedia for work characteristics. This research provides an in-depth insight of workers' unsafe behaviors by depicting the contributing factors as shown in the accident causal model developed in this research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Factors influencing behavior in the forced swim test

    PubMed Central

    Bogdanova, Olena V.; Kanekar, Shami; D’Anci, Kristen E.; Renshaw, Perry F.

    2017-01-01

    The forced swim test (FST) is a behavioral test in rodents which was developed in 1978 by Porsolt and colleagues as a model for predicting the clinical efficacy of antidepressant drugs. A modified version of the FST added the classification of active behaviors into swimming and climbing, in order to facilitate the differentiation between serotonergic and noradrenergic classes of antidepressant drugs. The FST is now widely used in basic research and the pharmaceutical screening of potential antidepressant treatments. It is also one of the most commonly used tests to assess depressive-like behavior in animal models. Despite the simplicity and sensitivity of the FST procedure, important differences even in baseline immobility rates have been reported between different groups, which complicate the comparison of results across studies. In spite of several methodological papers and reviews published on the FST, the need still exists for clarification of factors which can influence the procedure. While most recent reviews have focused on antidepressant effects observed with the FST, this one considers the methodological aspects of the procedure, aiming to summarize issues beyond antidepressant action in the FST. The previously published literature is analyzed for factors which are known to influence animal behavior in the FST. These include biological factors, such as strain, age, body weight, gender and individual differences between animals; influence of preconditioning before the FST: handling, social isolation or enriched environment, food manipulations, various kinds of stress, endocrine manipulations and surgery; schedule and routes of treatment, dosage and type of the drugs as well as experimental design and laboratory environmental effects. Consideration of these factors in planning experiments may result in more consistent FST results. PMID:23685235

  17. Motivating Factors Influencing College Students' Choice of Academic Major

    PubMed Central

    Brocavich, Joseph M.; Boone, R. Thomas; Pal, Somnath

    2010-01-01

    Objectives To assess the factors, motivations, and nonacademic influences that affected the choice of major among pharmacy and nonpharmacy undergraduate students. Methods A survey was administered to 618 pharmacy and nonpharmacy majors to assess background and motivational factors that may have influenced their choice of major. The sample consisted of freshman and sophomore students enrolled in a required speech course. Results African-American and Hispanic students were less likely to choose pharmacy as a major than Caucasians, whereas Asian-Americans were more likely to choose pharmacy as a major. Pharmacy students were more likely to be interested in science and math than nonpharmacy students. Conclusion Students' self-reported racial/ethnic backgrounds influence their decision of whether to choose pharmacy as their academic major. Results of this survey provide further insight into developing effective recruiting strategies and enhancing the marketing efforts of academic institutions. PMID:20498739

  18. Factors influencing tinnitus loudness and annoyance.

    PubMed

    Hiller, Wolfgang; Goebel, Gerhard

    2006-12-01

    To evaluate the 2 major components of tinnitus severity, loudness and annoyance, and their degree of dependence on characteristics of tinnitus manifestation, history, and etiology. Cross-sectional survey performed during the first months of 2004. Nonclinical population. A total of 4995 members of the German Tinnitus League. Comprehensive screening questionnaire, including the Klockhoff and Lindblom loudness grading system and the miniversion of the Tinnitus Questionnaire. A moderate correlation of 0.45 was found between tinnitus loudness and annoyance. Both factors were generally higher in men, those older than 50 years, those with binaural and centrally perceived tinnitus, those with increased noise sensitivity, and those who had continuous tinnitus without interruptions. Tinnitus that lasted 12 months or less had a stronger influence on annoyance (odds ratio [OR], 1.96) than on loudness (OR, 0.45), whereas the contrary was found for tinnitus of more than 5 years' duration (ORs, 0.72 and 2.11, respectively). Loudness and annoyance were increased in subjects with coexisting hearing loss, vertigo, and hyperacusis. The impact of hyperacusis on annoyance was clearly stronger than on loudness (ORs, 21.91 vs 9.47). Several clinical factors of tinnitus influence perceived loudness and annoyance. Both are distinguishable components of tinnitus severity.

  19. 29 CFR 98.860 - What factors may influence the debarring official's decision?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... your present responsibility. In making a debarment decision, the debarring official may consider the... 29 Labor 1 2010-07-01 2010-07-01 true What factors may influence the debarring official's decision... (NONPROCUREMENT) Debarment § 98.860 What factors may influence the debarring official's decision? This section...

  20. Factors influencing societal response of nanotechnology: an expert stakeholder analysis.

    PubMed

    Gupta, Nidhi; Fischer, Arnout R H; van der Lans, Ivo A; Frewer, Lynn J

    2012-05-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured interviews with experts on nanotechnology from North West Europe were conducted using repertory grid methodology in conjunction with generalized Procrustes analysis to examine the psychological constructs underlying societal uptake of 15 key applications of nanotechnology drawn from different areas (e.g. medicine, agriculture and environment, chemical, food, military, sports, and cosmetics). Based on expert judgement, the main factors influencing societal response to different applications of nanotechnology will be the extent to which applications are perceived to be beneficial, useful, and necessary, and how 'real' and physically close to the end-user these applications are perceived to be by the public. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11051-012-0857-x) contains supplementary material, which is available to authorized users.

  1. Factors influencing the pathways in response to complaints.

    PubMed

    Hsieh, Sophie Yahui

    2010-01-01

    The purpose of this paper is to explore hospital staff response to patient complaints and the factors influencing the response pathway. The paper uses an exploratory study in a large Taiwanese hospital purposefully chosen as a case study site. The critical incident technique (CIT) is implemented, using a questionnaire along with non-participant observations in which the results have been triangulated. A total of 59 cases were collected. The study found when facing "humaneness" complaints, hospital staff attempted to investigate the event and then explain the facts to the complainant or empathise with him/her and then refer the problem to the relevant unit. In response to complaints combining "communication" and "care/treatment and humaneness", staff tended to investigate the event's details and then directly explain them to the complainant. When complaints involved "care/treatment", staff tended to empathise with the complainant, investigate the facts and explain them to the complainant. Additionally, the organisational response to complaints was influenced by who made complaints; its type, severity, complaining method and patient status. The literature revealed that the case study is the most common organisational study method. However, this approach is criticised for not offering findings that can be generalised. Complaint nature is the major factor influencing the response pathway. If healthcare managers intend to reduce complaint rates then they need to carefully classify the complaint's nature. Different complaints have different handling procedures and guidelines to help managers resolve complaints in the first place. There are extensive studies focusing on investigating complaints and their resolution. These studies tend not to demonstrate various means of handling patient complaints. Neither do they describe how different complaints might lead to different outcomes. Therefore, this paper explores hospital staff response to patient complaints and the factors

  2. Factors influencing the incidence of maxillofacial fractures.

    PubMed

    Chrcanovic, Bruno Ramos

    2012-03-01

    Maxillofacial injuries occur in a significant proportion of trauma patients. Trauma causes considerable economic expense due to procedural costs, the time a patient is off work, and the associated loss of income. For these reasons, it is an important health and economic issue. The aim of this study is to discuss the factors that may influence the incidence of maxillofacial fractures. As it is necessary to determine trends to help guide the development of new methods of injury prevention, preventative measures are also discussed. An electronic search was undertaken in March 2011, including articles published between 1980 and 2011 with the terms "facial fractures" and "maxillofacial fractures" in the title. The texts of epidemiological studies were reviewed in order to identify factors that may influence the incidence of maxillofacial fractures. From the selected articles, ten factors were identified: age, gender, geographic region and cultural aspects, socioeconomic status, temporal and climatic influence, use of alcohol and drugs, compliance with road traffic legislation, domestic violence, osteoporosis, and etiology of the maxillofacial trauma. Care of injured patients should include not only management of the acute phase, but also combine preventive programs and interventional programs aimed at reducing the incidence of maxillofacial fractures. Therefore, there is a need to ensure strict compliance of traffic rules and regulations, implement improvement in automotive safety devices, organize prevention programs to minimize assaults, implement school education in alcohol abuse and handling potentially hostile situations (especially for men), improve protection during sporting activities, and legislate wearing of protective headgear in workers. Preventive strategies remain the cheapest way to reduce direct and indirect costs of the sequelae of trauma. Societal attitudes and behaviors must be modified before a significant reduction in the incidence of maxillofacial

  3. Organizational factors influencing successful primary care and public health collaboration.

    PubMed

    Valaitis, Ruta; Meagher-Stewart, Donna; Martin-Misener, Ruth; Wong, Sabrina T; MacDonald, Marjorie; O'Mara, Linda

    2018-06-07

    Public health and primary care are distinct sectors within western health care systems. Within each sector, work is carried out in the context of organizations, for example, public health units and primary care clinics. Building on a scoping literature review, our study aimed to identify the influencing factors within these organizations that affect the ability of these health care sectors to collaborate with one another in the Canadian context. Relationships between these factors were also explored. We conducted an interpretive descriptive qualitative study involving in-depth interviews with 74 key informants from three provinces, one each in western, central and eastern Canada, and others representing national organizations, government, or associations. The sample included policy makers, managers, and direct service providers in public health and primary care. Seven major organizational influencing factors on collaboration were identified: 1) Clear Mandates, Vision, and Goals; 2) Strategic Coordination and Communication Mechanisms between Partners; 3) Formal Organizational Leaders as Collaborative Champions; 4) Collaborative Organizational Culture; 5) Optimal Use of Resources; 6) Optimal Use of Human Resources; and 7) Collaborative Approaches to Programs and Services Delivery. While each influencing factor was distinct, the many interactions among these influences are indicative of the complex nature of public health and primary care collaboration. These results can be useful for those working to set up new or maintain existing collaborations with public health and primary care which may or may not include other organizations.

  4. Research on Influencing Factors of Salespeople's Empowerment Readiness in Green Energy Enterprise

    NASA Astrophysics Data System (ADS)

    Dong, Yuan; Liu, Xiaohui

    As market competition in green energy enterprises continues to intensify, marketing activities are enlarging and customer demand is increasingly growing and diversifying. More and more green energy enterprises have empowered their own salespeople. And managers in green energy enterprises are more concerned with the issues which employees suit to be empowered and which factors will influence employee empowerment readiness. This paper proposes the definition of salespeople's empowerment readiness, analyzes influencing factors of salespeople's empowerment readiness, discusses the effect mechanism of influencing factors of salespeople's empowerment readiness, finally, and puts forward some suggestions to enhance salespeople's empowerment readiness from the perspective of human resource management practice.

  5. Factors Which Influence The Fish Purchasing Decision: A study on Traditional Market in Riau Mainland

    NASA Astrophysics Data System (ADS)

    Siswati, Latifa; Putri, Asgami

    2018-05-01

    The purposes of the research are to analyze and assess the factors which influence fish purchasing by the community at Tenayan Raya district Pekanbaru.Research methodology which used is survey method, especially interview and observation technique or direct supervision on the market which located at Tenayan Raya district. Determination technique of sampling location/region is done by purposive sampling. The sampling method is done by accidental sampling. Technique analysis of factors which used using the data that derived from the respondent opinion to various fish variable. The result of this research are the factors which influence fish purchasing decision done in a traditional market which located at Tenayan Raya district are product factor, price factors, social factor and individual factor. Product factor which influences fish purchasing decision as follows: the eyelets condition, the nutrition of fresh fish, the diversity of sold fish. Price factors influence the fish purchasing decision, such as: the price of fresh fish, the convincing price and the suitability price and benefits of the fresh fish. Individual factors which influence a fish purchasing decision, such as education and income levels. Social factors which influence a fish purchasing decision, such as family, colleagues and feeding habits of fish.

  6. Factors Influencing Dietary Fat Intake among Black Emerging Adults

    ERIC Educational Resources Information Center

    Horton, Shalonda E. B.; Timmerman, Gayle M.; Brown, Adama

    2018-01-01

    Objective: To determine what factors influenced dietary fat intake (DFI) among black emerging adults. Participants: Sample included 251 black emerging adults, ages 18-25 years, living in the US. Methods: This was a nonexperimental cross-sectional study based on self-report data. Results: The sample had high DFI. Factors related to DFI were gender…

  7. Factors influencing elderly women's mammography screening decisions: implications for counseling.

    PubMed

    Schonberg, Mara A; McCarthy, Ellen P; York, Meghan; Davis, Roger B; Marcantonio, Edward R

    2007-11-16

    Although guidelines recommend that clinicians consider life expectancy before screening older women for breast cancer, many older women with limited life expectancies are screened. We aimed to identify factors important to mammography screening decisions among women aged 80 and older compared to women aged 65-79. Telephone surveys of 107 women aged 80+ and 93 women aged 65-79 randomly selected from one academic primary care practice who were able to communicate in English (60% response rate). The survey addressed the following factors in regards to older women's mammography screening decisions: perceived importance of a history of breast disease, family history of breast cancer, doctor's recommendations, habit, reassurance, previous experience, mailed reminder cards, family/friend's recommendations or experience with breast cancer, age, health, and media. The survey also assessed older women's preferred role in decision making around mammography screening. Of the 200 women, 65.5% were non-Hispanic white and 82.8% were in good to excellent health. Most (81.3%) had undergone mammography in the past 2 years. Regardless of age, older women ranked doctor's recommendations as the most important factor influencing their decision to get screened. Habit and reassurance were the next two highly ranked factors influencing older women to get screened. Among women who did not get screened, women aged 80 and older ranked age and doctor's counseling as the most influential factors and women aged 65-79 ranked a previous negative experience with mammography as the most important factor. There were no significant differences in preferred role in decision-making around mammography screening by age, however, most women in both age groups preferred to make the final decision on their own (46.6% of women aged 80+ and 50.5% of women aged 65-79). While a doctor's recommendation is the most important factor influencing elderly women's mammography screening decisions, habit and reassurance

  8. Factors influencing exacerbation-related self-management in patients with COPD: a qualitative study.

    PubMed

    Korpershoek, Yjg; Vervoort, Scjm; Nijssen, Lit; Trappenburg, Jca; Schuurmans, M J

    2016-01-01

    In patients with COPD, self-management skills are important to reduce the impact of exacerbations. However, both detection and adequate response to exacerbations appear to be difficult for some patients. Little is known about the underlying process of exacerbation-related self-management. Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior. A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated. Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015. Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed. Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management. Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms. Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions. This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients. The conceptual model can be used as a framework for health care professionals providing self-management support. In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account.

  9. Factors influencing endometrial thickness in postmenopausal women.

    PubMed

    Hebbar, S; Chaya, V; Rai, L; Ramachandran, A

    2014-07-01

    Cut-off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause. To study the various factors influencing the ET in postmenopausal women. This was a prospective observational study. A total of 110 postmenopausal women underwent detailed history taking, clinical examination, and transvaginal scan for uterine volume and ovarian volume. The volumes were calculated by using ellipsoid formula: Width × thickness × height × 0.523. The variation in ET with respect to the influencing factors such as age, duration of menopause, parity, body mass index (BMI), medical illness like diabetes/hypertension, drugs like tamoxifen, presence of myoma, uterine volume, ovarian volume, and serum estradiol (in selected patients) were measured. Descriptive analysis was performed using SPSS software (version 16, Chicago II, USA) to obtain mean, standard deviation (SD), 95% confidence intervals (CIs) and inter quartile ranges. Comparison of means was carried out using analysis of variance. The mean (SD) age of the patients was 55.4 (6.91) years (95% CI, 54.1, 56.7). The mean (SD) age at menopause was 47.95 (3.90) years (95% CI, 47.2, 48.7) and the mean (SD) duration of menopause was 7.27 (6.65) years (95% CI, 6.01, 8.53). The mean (SD) ET was 3.8 (2.3) mm (95% CI, 3.36, 4.23). Medical illness like diabetes and hypertension did not alter the ET. ET increased as BMI increased and it was statistically significant. The presence of myoma increased uterine volume significantly and was associated with thick endometrial stripe. Similarly, whenever the ovaries were visualized and as the ovarian volume increased, there was an increase in ET. When ET was > 4 mm (n = 37), they were offered endocel, of which 16 agreed to undergo the procedure. None were found to have endometrial cancer. This study suggests that parity, BMI, presence of

  10. Factors Influencing Adjustment to Late-Life Divorce.

    ERIC Educational Resources Information Center

    Wilson, Keren Brown; DeShane, Michael R.

    Although the rate of divorce among older Americans has increased steadily, little attention has been paid to late life divorce. To describe the role of age and other factors which might influence adjustment to divorce in later life, data from a larger pilot study were used: 81 divorced persons over the age of 60 completed in-depth, structured…

  11. The influence of natural factors on the spatio-temporal distribution of Oncomelania hupensis.

    PubMed

    Cheng, Gong; Li, Dan; Zhuang, Dafang; Wang, Yong

    2016-12-01

    We analyzed the influence of natural factors, such as temperature, rainfall, vegetation and hydrology, on the spatio-temporal distribution of Oncomelania hupensis and explored the leading factors influencing these parameters. The results will provide reference methods and theoretical a basis for the schistosomiasis control. GIS (Geographic Information System) spatial display and analysis were used to describe the spatio-temporal distribution of Oncomelania hupensis in the study area (Dongting Lake in Hunan Province) from 2004 to 2011. Correlation analysis was used to detect the natural factors associated with the spatio-temporal distribution of O. hupensis. Spatial regression analysis was used to quantitatively analyze the effects of related natural factors on the spatio-temporal distribution of snails and explore the dominant factors influencing this parameter. (1) Overall, the spatio-temporal distribution of O. hupensis was governed by the comprehensive effects of natural factors. In the study area, the average density of living snails showed a downward trend, with the exception of a slight rebound in 2009. The density of living snails showed significant spatial clustering, and the degree of aggregation was initially weak but enhanced later. Regions with high snail density and towns with an HH distribution pattern were mostly distributed in the plain areas in the northwestern and inlet and outlet of the lake. (2) There were space-time differences in the influence of natural factors on the spatio-temporal distribution of O. hupensis. Temporally, the comprehensive influence of natural factors on snail distribution increased first and then decreased. Natural factors played an important role in snail distribution in 2005, 2006, 2010 and 2011. Spatially, it decreased from the northeast to the southwest. Snail distributions in more than 20 towns located along the Yuanshui River and on the west side of the Lishui River were less affected by natural factors, whereas

  12. Factors Influencing the Effectiveness of Inventory Management in Manufacturing SMEs

    NASA Astrophysics Data System (ADS)

    Chan, Shiau Wei; Tasmin, R.; Nor Aziati, A. H.; Zuraidah Rasi, Raja; Ismail, Fadillah Binti; Yaw, Li Ping

    2017-08-01

    Effectiveness of inventory management is a vital part in the manufacturing organization to be more competitive. The previous studies have indicated that there are several factors influencing the effectiveness of inventory management in the organization but there is lack of researchers who carried out the research in the manufacturing small medium enterprise in Johor. Therefore, the purpose of this research is to identify the problem of inventory management faced by the manufacturing small medium enterprise and also to determine the factors that will influence the effectiveness of inventory management. In completing this research, 80 employees were selected randomly from the manufacturing small medium enterprise in Batu Pahat, Johor and they were requested to complete questionnaires. The result have shown that the problems of inventory management faced by manufacturing organization were underproduction, overproduction, stock out situation, delays in the delivery of raw materials and discrepancy of records. The factors, documentation/store records, planning, knowledge of employees/staff skill have shown to significantly influence the effectiveness of inventory management while the funds have shown slightly significant influence on the inventory management in manufacturing small medium enterprises. This quantitative study is important to the manufacturing organization in Malaysia because it provides the guidelines to the employers of manufacturing small medium enterprises in Batu Pahat, Johor.

  13. Factors influencing the occupational trajectory of patients with systemic sclerosis: a qualitative study.

    PubMed

    Decuman, Saskia; Smith, Vanessa; Grypdonck, Maria; De Keyser, Filip; Verhaeghe, Sofie

    2015-01-01

    To describe, from the patient's point of view, the factors influencing the occupational trajectory of patients with systemic sclerosis (SSc). This was a qualitative study designed using grounded theory with constant comparison. Data were collected through semi-structured interviews with 14 patients who fulfilled the American College of Rheumatology or Leroy-Medsger criteria for SSc. Based on our interviews, we found that the occupational trajectory of patients with SSc is influenced by the continuous interplay between four groups of factors. The first group concerns the values patients attribute to work, including identity, normality, financial value, social contact, and structure. The meaning of these values and how they relate to each other underlies the desire to work. A second group of factors is those influencing the balance between daily life, work participation, and medical condition (e.g. job content, flexibility in organising work, and the willingness to ask for accommodations at work). The occupational trajectory is also influenced by external factors, including availability of support, know-ledge of the disease, pressure to work, contact with medical professionals, and existing regulations and the patient's knowledge about them. Finally, the occupational trajectory is influenced by personal factors, including socio-demographics, psychological assets, and disease- and work-related personal factors. The decisions patients with SSc take concerning work depend on an interplay between many factors and, especially, on the patients' personal interpretation of these factors. These need to be taken into account when helping patients with SSc determine their occupational trajectory.

  14. Factors Influencing New RNs' Supervisory Performance in Long-Term Care Facilities.

    PubMed

    Prentice, Dawn; Boscart, Veronique; McGilton, Katherine S; Escrig, Astrid

    2017-12-01

    In long-term care facilities (LTCF), registered nurses (RNs) perform both clinical and supervisory roles as part of a team aiming to provide high-quality care to residents. The residents have several co-morbidities and complex care needs. Unfortunately, new RNs receive minimal preparation in gerontology and supervisory experience during their program, leading to low retention rates and affecting resident outcomes. This qualitative study explored factors that influence supervisory performance of new RNs in LTCF from the perspective of 24 participants from Ontario, Canada. Data were collected through individual interviews, followed by a directed content analysis. Three levels of influences were identified: personal influences, organizational influences, and external influences. Each level presented with sub-elements, further describing the factors that impact the supervisory performance of the new RN. To retain new RNs in LTC, organizations must provide additional gerontological education and mentoring for new RNs to flourish in their supervisory roles.

  15. Factors influencing food choice of athletes at international competition events.

    PubMed

    Pelly, Fiona E; Burkhart, Sarah J; Dunn, Peter

    2018-02-01

    Although the nutrient requirements and dietary intake of athletes have been thoroughly investigated, little is known about the influences on their food choice, particularly prior to and during competition. This study sought to investigate factors that influence food selection of athletes at two similar international competition events: the Melbourne 2006 and Delhi 2010 Commonwealth Games. A secondary aim was to explore differences in these factors between at each event given the culturally diverse locations. A survey developed for this study was distributed to athletes in the village dining hall at both events. Athletes scored a selection of factors influencing food choice on a scale of 1 (not important) to 5 (very important). A total of 769 individuals completed the questionnaire in total, with 351 (46%) from Delhi and 418 (54%) from Melbourne. Overall, athletes rated nutrient composition (M = 4.22), stage of competition (M = 4.09), time of day (M = 4.02) and familiarity of the food (M = 4.07) higher than sensory properties (smell M = 3.88; visual appearance M = 3.22) when making a food selection. Visual appearance (p = 0.01), stage of competition (p < 0.001) and time of day (p = 0.01) had greater influence in Delhi than Melbourne. Overall, a significantly higher proportion of female athletes rated smell (p < 0.001) and familiar food (p < 0.001) as important compared to males. The stage of competition and nutrition composition was rated as very important by the greatest proportion of athletes from weight category sports (61.9%) and endurance sports (57.9%) respectively. The influence of the coach and team mates was less of an influence than other factors, but more so for athletes from Non-Western regions. Further investigation of the various determinants and motives for food section of athletes from a range of sports and cultures is warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Factors influencing deprescribing habits among geriatricians.

    PubMed

    Ní Chróinín, Danielle; Ní Chróinín, Chantelle; Beveridge, Alexander

    2015-07-01

    deprescribing habits among physicians managing older, frailer, cognitively impaired patients have not been well investigated. an anonymised electronic survey was disseminated to all members of an international geriatric society/local advanced trainee network (N = 930). This comprised a Likert-scale analysis of factors influencing desprescribing, and five case vignettes, detailing a patient with progressive cognitive impairment and dependency, on a background of ischaemic heart disease and hypertension. among 134 respondents (response rate 14.4%), 47.4% were female, 48.9% aged 36-50 years and 84.1% specialists (15.9% trainees). Respondents commonly rated limited life expectancy (96.2%) and cognitive impairment (84.1%) as very/extremely important to deprescribing practices. On multivariable analysis, older respondents less commonly rated functional dependency (odds ratio [OR] 0.22 per change in age category; P < 0.001) and limited life expectancy (OR 0.09, P = 0.04) important when deprescribing, while female participants (OR 3.03, P < 0.001) and trainees (versus specialists OR 14.29, P < 0.001) more often rated adherence to evidence-based guidelines important. As vignettes described increasing dependency and cognitive impairment, physicians were more likely to stop donepezil, aspirin, atorvastatin and antihypertensives (all P < 0.001 for trend). Aspirin (93.6%) and ramipril (94.1%) were most commonly deprescribed. Commonest reasons cited for deprescribing medications were 'dementia severity', followed by pill burden. in this exploratory analysis, geriatricians rated limited life expectancy and cognitive impairment very important in driving deprescribing practices. Geriatricians more often deprescribed multiple medications in the setting of advancing dependency and cognitive impairment, driven by dementia severity and pill burden concerns. Physician characteristics also influence deprescribing practices. Further exploration of factors influencing deprescribing

  17. Influencing Factors of the Initiation Point in the Parachute-Bomb Dynamic Detonation System

    NASA Astrophysics Data System (ADS)

    Qizhong, Li; Ye, Wang; Zhongqi, Wang; Chunhua, Bai

    2017-12-01

    The parachute system has been widely applied in modern armament design, especially for the fuel-air explosives. Because detonation of fuel-air explosives occurs during flight, it is necessary to investigate the influences of the initiation point to ensure successful dynamic detonation. In fact, the initiating position exist the falling area in the fuels, due to the error of influencing factors. In this paper, the major influencing factors of initiation point were explored with airdrop and the regularity between initiation point area and factors were obtained. Based on the regularity, the volume equation of initiation point area was established to predict the range of initiation point in the fuel. The analysis results showed that the initiation point appeared area, scattered on account of the error of attitude angle, secondary initiation charge velocity, and delay time. The attitude angle was the major influencing factors on a horizontal axis. On the contrary, secondary initiation charge velocity and delay time were the major influencing factors on a horizontal axis. Overall, the geometries of initiation point area were sector coupled with the errors of the attitude angle, secondary initiation charge velocity, and delay time.

  18. Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    PubMed Central

    Kantarjian, Hagop M.; Thomas, Xavier G.; Dmoszynska, Anna; Wierzbowska, Agnieszka; Mazur, Grzegorz; Mayer, Jiri; Gau, Jyh-Pyng; Chou, Wen-Chien; Buckstein, Rena; Cermak, Jaroslav; Kuo, Ching-Yuan; Oriol, Albert; Ravandi, Farhad; Faderl, Stefan; Delaunay, Jacques; Lysák, Daniel; Minden, Mark; Arthur, Christopher

    2012-01-01

    Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unplanned analysis with 446 deaths (92%) indicated the same median OS (HR, 0.82; 95% CI, 0.68 to 0.99; nominal P = .037). The CR rate plus CRp was 17.8% with decitabine versus 7.8% with TC (odds ratio, 2.5; 95% CI, 1.4 to 4.8; P = .001). AEs were similar for decitabine and cytarabine, although patients received a median of four cycles of decitabine versus two cycles of TC. The most common drug-related AEs with decitabine were thrombocytopenia (27%) and neutropenia (24%). Conclusion In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety. An unplanned survival analysis showed a benefit for decitabine, which was not observed at the time of the primary analysis. PMID:22689805

  19. [Prevalence and influence factors of hypertension among mechanic factory workers].

    PubMed

    Pang, Li-Juan; Chen, Li-Zhang; Fu, Ben-Yan

    2005-06-01

    To determine the status and influence factors of hypertension on mechanic factory workers and to provide reference for further hypertension prevention and control. A cross-sectional study on 1205 workers (exposed to different noise levels) in Hunan was carried out by using questionaire and measuring the blood pressure of the workers and the noise exposure level in the workplace. The prevalence and the influence factors of hypertension among mechanic factory workers were analysed. The hypertension prevalence was 12.1%. Logistic regression analysis showed the body weight index (BMI), age, and history of hypertension in parents and accumulative noise dose levels influenced the hypertension prevalence. Controlling the body weight, reducing alcohol consumption, decreasing the sound pressure level in workshops and advocating healthy diet may reduce the prevalence rate of hypertension among mechanic factory workers.

  20. Factors Influencing New Entrant Dairy Farmer's Decision-Making Process around Technology Adoption

    ERIC Educational Resources Information Center

    McDonald, Roberta; Heanue, Kevin; Pierce, Karina; Horan, Brendan

    2016-01-01

    Purpose: The aims of this paper are to (1) evaluate the main factors influencing grazing system technology adoption among new entrant (NE) dairy farmers within Europe and the Irish pasture-based dairy industry, and (2) to determine the extent to which economic factors influence decision-making around technology adoption and use among NEs to the…

  1. Logistic Regression and Path Analysis Method to Analyze Factors influencing Students’ Achievement

    NASA Astrophysics Data System (ADS)

    Noeryanti, N.; Suryowati, K.; Setyawan, Y.; Aulia, R. R.

    2018-04-01

    Students' academic achievement cannot be separated from the influence of two factors namely internal and external factors. The first factors of the student (internal factors) consist of intelligence (X1), health (X2), interest (X3), and motivation of students (X4). The external factors consist of family environment (X5), school environment (X6), and society environment (X7). The objects of this research are eighth grade students of the school year 2016/2017 at SMPN 1 Jiwan Madiun sampled by using simple random sampling. Primary data are obtained by distributing questionnaires. The method used in this study is binary logistic regression analysis that aims to identify internal and external factors that affect student’s achievement and how the trends of them. Path Analysis was used to determine the factors that influence directly, indirectly or totally on student’s achievement. Based on the results of binary logistic regression, variables that affect student’s achievement are interest and motivation. And based on the results obtained by path analysis, factors that have a direct impact on student’s achievement are students’ interest (59%) and students’ motivation (27%). While the factors that have indirect influences on students’ achievement, are family environment (97%) and school environment (37).

  2. A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study (POE 10-03).

    PubMed

    Cooper, Todd M; Sison, Edward Allan Racela; Baker, Sharyn D; Li, Lie; Ahmed, Amina; Trippett, Tanya; Gore, Lia; Macy, Margaret E; Narendran, Aru; August, Keith; Absalon, Michael J; Boklan, Jessica; Pollard, Jessica; Magoon, Daniel; Brown, Patrick A

    2017-08-01

    Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m 2 /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily). Nineteen patients (13 with AML, 5 with ALL, 1 with MDS) were treated. The most common grade 3 or greater nonhematologic toxicities attributable to plerixafor were febrile neutropenia and hypokalemia. There were no dose-limiting toxicities (DLTs). Plerixafor exposure increased with increasing dose levels and clearance was similar on days 1 and 5. Eighteen patients were evaluable for response. Two patients achieved complete remission (CR) and one patient achieved CR with incomplete hematologic recovery (CRi): all three had AML. No responses were seen in patients with ALL or MDS. Plerixafor mobilized leukemic blasts into the peripheral blood in 14 of 16 evaluable patients (median 3.4-fold increase), and the degree of mobilization correlated with surface CXCR4 expression. Plerixafor, in combination with high-dose cytarabine and etoposide, was well tolerated in children and young adults with relapsed/refractory acute leukemias and MDS. While biologic responses were observed, clinical responses in this heavily pretreated cohort were modest. © 2017 Wiley Periodicals, Inc.

  3. [Coagulation factor VII levels in uremic patients and theirs influence factors].

    PubMed

    Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

    2004-12-01

    This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

  4. Automation bias: empirical results assessing influencing factors.

    PubMed

    Goddard, Kate; Roudsari, Abdul; Wyatt, Jeremy C

    2014-05-01

    To investigate the rate of automation bias - the propensity of people to over rely on automated advice and the factors associated with it. Tested factors were attitudinal - trust and confidence, non-attitudinal - decision support experience and clinical experience, and environmental - task difficulty. The paradigm of simulated decision support advice within a prescribing context was used. The study employed within participant before-after design, whereby 26 UK NHS General Practitioners were shown 20 hypothetical prescribing scenarios with prevalidated correct and incorrect answers - advice was incorrect in 6 scenarios. They were asked to prescribe for each case, followed by being shown simulated advice. Participants were then asked whether they wished to change their prescription, and the post-advice prescription was recorded. Rate of overall decision switching was captured. Automation bias was measured by negative consultations - correct to incorrect prescription switching. Participants changed prescriptions in 22.5% of scenarios. The pre-advice accuracy rate of the clinicians was 50.38%, which improved to 58.27% post-advice. The CDSS improved the decision accuracy in 13.1% of prescribing cases. The rate of automation bias, as measured by decision switches from correct pre-advice, to incorrect post-advice was 5.2% of all cases - a net improvement of 8%. More immediate factors such as trust in the specific CDSS, decision confidence, and task difficulty influenced rate of decision switching. Lower clinical experience was associated with more decision switching. Age, DSS experience and trust in CDSS generally were not significantly associated with decision switching. This study adds to the literature surrounding automation bias in terms of its potential frequency and influencing factors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Factors influencing a problem-based learning implementation: A case study of IT courses

    NASA Astrophysics Data System (ADS)

    Darus, Norida Muhd; Mohd, Haslina; Baharom, Fauziah; Saip, Mohamed Ali; Puteh, Nurnasran; Marzuki @ Matt, Zaharin; Husain, Mohd Zabidin; Yasin, Azman

    2016-08-01

    IT students must be trained to work efficiently as teamwork. One of the techniques that can be used to train them is through Problem-Based Learning (PBL) approach. The PBL implementation can be influenced by various factors depending on the ultimate goal of the study. This study is focusing on the IT students' perception of the PBL implementation. The student's perception is important to ensure the successfulness of the PBL implementation. Therefore, it is important to identify the factors that might influence the implementation of PBL of IT courses. This study aims to identify some catalyst factors that may influence the PBL implementation of IT courses. The study involved three (3) main phases: identifying PBL implementation factors, constructing a PBL model, and PBL model validation using statistical analysis. Four main factors are identified: PBL Characteristics, PBL Course Assessment, PBL Practices, and PBL Perception. Based on these four factors, a PBL model is constructed. Then, based on the proposed PBL model, four hypotheses are formulated and analyzed to validate the model. All hypotheses are significantly acceptable. The result shows that the PBL Characteristics and PBL Course Assessment factors are significantly influenced the PBL Practices and indirectly influenced the Students' Perception of the PBL Implementation for IT courses. This PBL model can assist decision makers in enhancing the PBL teaching and learning strategy for IT courses. It is also can be tested to other courses in the future.

  6. A Survey of the Influencing Factors for International Academic Mobility of Chinese University Students

    ERIC Educational Resources Information Center

    Cao, Chun; Zhu, Chang; Meng, Qian

    2016-01-01

    This research aims to understand the factors influencing international academic mobility within the Chinese higher education context. The inventory of University Students' Perceptions of Influencing Factors for International Academic Mobility was developed and tested to enquire about Chinese university students' perceptions of factors influencing…

  7. The influence of ergonomic factors and perceptual-motor abilities on handwriting performance.

    PubMed

    Tseng, M H; Cermak, S A

    1993-10-01

    Difficulty with handwriting is one of the most frequent reasons that children in the public schools are referred to occupational therapy. Current research on the influence of ergonomic factors, such as pencil grip and pressure, and perceptual-motor factors traditionally believed to affect handwriting, is reviewed. Factors such as visual perception show little relationship to handwriting, whereas tactile-kinesthetic, visual-motor, and motor planning appear to be more closely related to handwriting. By better understanding the ergonomic and perceptual-motor factors that contribute to and influence handwriting, therapists will be better able to design rationally based intervention programs.

  8. What factors influence cataract waiting list time?

    PubMed Central

    Churchill, A.; Vize, C.; Stewart, O.; Backhouse, O.

    2000-01-01

    AIMS—To determine whether there were any specific factors that influenced waiting list time (WLT) for patients undergoing cataract surgery.
METHODS—70 preoperative cataract patients were interviewed by one of the authors using a questionnaire to score visual acuity, coexisting ocular pathology and disabilities, threat to independent living/employment, and perceived visual handicap for detailed, gross, and driving vision. Individuals were analysed separately according to whether it was their first or second cataract operation.
RESULTS—The median WLT for first eye surgery was 9 months (n = 31) and 13 months for second eye surgery (n = 36). The WLT ranged from 2 to 25 months for first eyes and 0.25-18 months for second eyes. Where there was a perceived threat to independent living or employment the WLT was found to be significantly shorter than the median. A high overall score correlated with a shorter WLT. Surgical priority was also given to individuals with anisometropia >3 dioptres.
CONCLUSION—This study has demonstrated that there are specific factors that influence clinicians when prioritising patients for cataract surgery.

 PMID:10729304

  9. 22 CFR 1006.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true What factors may influence the debarring official during reconsideration? 1006.880 Section 1006.880 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Debarment § 1006.880 What factors may influence the...

  10. 7 CFR 3017.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false What factors may influence the debarring official during reconsideration? 3017.880 Section 3017.880 Agriculture Regulations of the Department of... DEBARMENT AND SUSPENSION (NONPROCUREMENT) Debarment § 3017.880 What factors may influence the debarring...

  11. 22 CFR 1508.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true What factors may influence the debarring official during reconsideration? 1508.880 Section 1508.880 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Debarment § 1508.880 What factors may influence the...

  12. 5 CFR 919.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false What factors may influence the debarring official during reconsideration? 919.880 Section 919.880 Administrative Personnel OFFICE OF PERSONNEL... (NONPROCUREMENT) Debarment § 919.880 What factors may influence the debarring official during reconsideration? The...

  13. Differential factors that influence applicant selection of a prosthodontic residency program.

    PubMed

    Blissett, Ryan; Lee, Meng-Chieh; Jimenez, Monik; Sukotjo, Cortino

    2009-04-01

    The main objectives of this study were to identify current prosthodontic resident demographics and to analyze factors that may influence applicants in selecting prosthodontics as a career, as well as a specific prosthodontic program. We also investigated the influence of age, gender, relationship status, and year in program on applicant decisions. Two questionnaires were mailed to all prosthodontic residents (N = 304) registered with the American College of Prosthodontists (ACP) Central Office. Part I assessed resident demographics and factors influencing choice of specialty. Part II assessed factors influencing the selection of a specific prosthodontic program. Completed surveys were obtained from 193 of 304 (63.4%) of all prosthodontic residents registered at the ACP Central Office. The completed surveys represented approximately 48% of the total population of prosthodontic residents in the United States. Demographic data revealed that 37% and 62% of the respondents were female and male, respectively (1% did not report gender). The mean age of the respondents was 30.3 years. More residents reported being married than either single or in a relationship. Most residents were accepted to their top choice program. Part I of the survey revealed that the complexity and challenge of treatment planning/treatment, ability to lead multidisciplinary cases, possession of skills/talents suited to the specialty, enjoyment of clinical work, and the intellectual content of the specialty were reported to be the five most influential factors in choosing prosthodontics as a career. Part II demonstrated that applicants place a high emphasis on clinical education, their impression of the program director, advice from predoctoral mentors, their impression of resident satisfaction and happiness, and the opportunity to place dental implants. The factors of least importance are climate and opportunities to moonlight, teach, and conduct research. Dental students consider the complexity and

  14. Analysis of Spatial Pattern and Influencing Factors of E-Commerce

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Chen, J.; Zhang, S.

    2017-09-01

    This paper aims to study the relationship between e-commerce development and geographical characteristics using data of e-commerce, economy, Internet, express delivery and population from 2011 to 2015. Moran's I model and GWR model are applied to analyze the spatial pattern of E-commerce and its influencing factors. There is a growth trend of e-commerce from west to east, and it is obvious to see that e-commerce development has a space-time clustering, especially around the Yangtze River delta. The comprehensive factors caculated through PCA are described as fundamental social productivity, resident living standard and population sex structure. The first two factors have positive correlation with e-commerce, and the intensity of effect increases yearly. However, the influence of population sex structure on the E-commerce development is not significant. Our results suggest that the clustering of e-commerce has a downward trend and the impact of driving factors on e-commerce is observably distinct from year to year in space.

  15. Factors influencing physicians' knowledge sharing on web medical forums.

    PubMed

    Lin, Tung Cheng; Lai, Ming Cheng; Yang, Shu Wen

    2016-09-01

    Web medical forums are relatively unique as knowledge-sharing platforms because physicians participate exclusively as knowledge contributors and not as knowledge recipients. Using the perspective of social exchange theory and considering both extrinsic and intrinsic motivations, this study aims to elicit the factors that significantly influence the willingness of physicians to share professional knowledge on web medical forums and develops a research model to explore the motivations that underlie physicians' knowledge-sharing attitudes. This model hypothesizes that constructs, including shared vision, reputation, altruism, and self-efficacy, positively influence these attitudes and, by extension, positively impact knowledge-sharing intention. A conventional sampling method and the direct recruitment of physicians at their outpatient clinic gathered valid data from a total of 164 physicians for analysis in the model. The empirical results support the validity of the proposed model and identified shared vision as the most significant factor of influence on knowledge-sharing attitudes, followed in descending order by knowledge-sharing self-efficacy, reputation, and altruism. © The Author(s) 2015.

  16. Analysis on influencing factors of EV charging station planning based on AHP

    NASA Astrophysics Data System (ADS)

    Yan, F.; Ma, X. F.

    2016-08-01

    As a new means of transport, electric vehicle (EV) is of great significance to alleviate the energy crisis. EV charging station planning has a far-reaching significance for the development of EV industry. This paper analyzes the impact factors of EV charging station planning, and then uses the analytic hierarchy process (AHP) to carry on the further analysis to the influencing factors, finally it gets the weight of each influence factor, and provides the basis for the evaluation scheme of the planning of charging stations for EV.

  17. Influence of gender and other factors on medical student specialty interest.

    PubMed

    Boyle, Veronica; Shulruf, Boaz; Poole, Phillippa

    2014-09-12

    Medical schools must select and educate to meet anticipated health needs. Factors influencing career choice include those of the student and their background as well as subsequent experience. Women have comprised over 50% of medical classes for over 20 years. This study describes gender patterns of current specialty interest among medical students at the University of Auckland, and models the predictive effect of gender compared to other career influencing factors. The study analysed career intention survey data from 711 graduating medical students (response rate, 79%) from 2006 to 2011. Interest level was highest for medicine, followed by subspecialty surgery, general practice and paediatrics. There were differences by gender for most specialties, but not for general practice. Women were more likely than men to be interested in Obstetrics and Gynaecology, Paediatrics, Geriatrics, Public Health or General Medicine, and less interested in Surgery, Anaesthesia, Emergency Medicine or post graduate study. Each specialty had a different pattern of influencing factors with the most important factor being the experience on a clinical attachment. Factors in career choice are complex and vary by gender and specialty. General practice levels of interest are too low for workforce needs. Predictive models need to be validated in longer term studies but may help guide selection and curriculum design.

  18. 2 CFR 180.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false What factors may influence the debarring official during reconsideration? 180.880 Section 180.880 Grants and Agreements OFFICE OF MANAGEMENT AND... GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Debarment § 180.880 What factors may influence the...

  19. 34 CFR 85.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false What factors may influence the debarring official during reconsideration? 85.880 Section 85.880 Education Office of the Secretary, Department of Education GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Debarment § 85.880 What factors may influence the...

  20. Factors Influencing Residents' Satisfaction in Residential Aged Care

    ERIC Educational Resources Information Center

    Chou, Shu-Chiung; Boldy, Duncan P.; Lee, Andy H.

    2003-01-01

    Purpose: The aim of this study was to identify the important factors influencing residents' satisfaction in residential aged care and to provide a better understanding of their interrelationships. Design and Methods: A cross-sectional survey design was used to collect the required information, including resident satisfaction, resident dependency…

  1. Factors that Influence Informal Learning in the Workplace

    ERIC Educational Resources Information Center

    Berg, Shelley A.; Chyung, Seung Youn

    2008-01-01

    Purpose: The purpose of this research is to investigate factors that influence informal learning in the workplace and the types of informal learning activities people engage in at work. More specifically, the research examined: the relationship between informal learning engagement and the presence of learning organization characteristics; and…

  2. Factors Influencing Consumers Intention for Online Grocery Shopping - A Proposed Framework

    NASA Astrophysics Data System (ADS)

    Pauzi, SFF; Thoo, AC; Tan, LC; Muharam, FM; Talib, NA

    2017-06-01

    Nowadays, Internet is one of the most popular platforms for people to do online shopping including grocery items. Many studies have been conducted to investigate the determinants of customer intentions for online grocery shopping. Till now, there is no consensus on what are the factors that actually influencing people to shop grocery items through Internet. This paper aims to explore the factors such as social influences, facilitating conditions, hedonic motivations, perceived risk and perceived trust that influence the consumer intention to purchase grocery online. Questionnaires will be the main instrument of the study and they will be distributed to target respondents using Internet survey. Respondents of the study will be selected using convenience sampling. After data collection, Statistical Package for the Social Sciences (SPSS) will be employed for data analysis. Overall, the result of the study is important to retailers to identify the important factors in increasing their customers’ intention to purchase grocery online.

  3. Leadership styles of Finnish nurse managers and factors influencing it.

    PubMed

    Vesterinen, Soili; Isola, Arja; Paasivaara, Leena

    2009-05-01

    The purpose of the present study was to explore nurse managers' perceptions of their leadership styles and factors influencing it. It is a challenge for nurse managers to retain nurses in hospitals and to ensure a high quality of care in nursing practice. Leadership style is an important part of leadership. Knowledge concerning nurse managers' resonant and non-resonant leadership styles provides nurse managers with tools to reflect on their own leadership style. Open-ended, tape-recorded interviews were conducted with 13 nurse managers from five Finnish hospitals and two long-term care facilities. The data were analysed using qualitative content analysis. Five categories of leadership style were discerned: visionary, coaching, affiliate, democratic, commanding. Factors that influence leadership style were identified: earlier superiors, values, information, cooperation, employees and education. The results of this study show that Finnish nurse managers use both resonant and non-resonant leadership styles. The findings of this study show that nurse managers use a variety of leadership styles. The study demonstrates the importance of knowledge about leadership styles and factors influencing it among nurse managers providing future leadership and management education.

  4. 41 CFR 105-68.860 - What factors may influence the debarring official's decision?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... responsibility. In making a debarment decision, the debarring official may consider the following factors: (a... influence the debarring official's decision? 105-68.860 Section 105-68.860 Public Contracts and Property...) Debarment § 105-68.860 What factors may influence the debarring official's decision? This section lists the...

  5. 29 CFR 98.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true What factors may influence the debarring official during reconsideration? 98.880 Section 98.880 Labor Office of the Secretary of Labor GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Debarment § 98.880 What factors may influence the debarring official during...

  6. 31 CFR 19.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false What factors may influence the debarring official during reconsideration? 19.880 Section 19.880 Money and Finance: Treasury Office of the... factors may influence the debarring official during reconsideration? The debarring official may reduce or...

  7. Genetic Factors Influence Serological Measures of Common Infections

    PubMed Central

    Rubicz, Rohina; Leach, Charles T.; Kraig, Ellen; Dhurandhar, Nikhil V.; Duggirala, Ravindranath; Blangero, John; Yolken, Robert; Göring, Harald H.H.

    2011-01-01

    Background/Aims Antibodies against infectious pathogens provide information on past or present exposure to infectious agents. While host genetic factors are known to affect the immune response, the influence of genetic factors on antibody levels to common infectious agents is largely unknown. Here we test whether antibody levels for 13 common infections are significantly heritable. Methods IgG antibodies to Chlamydophila pneumoniae, Helicobacter pylori, Toxoplasma gondii, adenovirus 36 (Ad36), hepatitis A virus, influenza A and B, cytomegalovirus, Epstein-Barr virus, herpes simplex virus (HSV)-1 and −2, human herpesvirus-6, and varicella zoster virus were determined for 1,227 Mexican Americans. Both quantitative and dichotomous (seropositive/seronegative) traits were analyzed. Influences of genetic and shared environmental factors were estimated using variance components pedigree analysis, and sharing of underlying genetic factors among traits was investigated using bivariate analyses. Results Serological phenotypes were significantly heritable for most pathogens (h2 = 0.17–0.39), except for Ad36 and HSV-2. Shared environment was significant for several pathogens (c2 = 0.10–0.32). The underlying genetic etiology appears to be largely different for most pathogens. Conclusions Our results demonstrate, for the first time for many of these pathogens, that individual genetic differences of the human host contribute substantially to antibody levels to many common infectious agents, providing impetus for the identification of underlying genetic variants, which may be of clinical importance. PMID:21996708

  8. Psychosocial Factors Influencing Competency of Children's Statements on Sexual Trauma

    ERIC Educational Resources Information Center

    Kim, Tae Kyung; Choi, Soul; Shin, Yee Jin

    2011-01-01

    Objectives: The objectives of this study are to assess children's competence to state their traumatic experience and to determine psychosocial factors influencing the competency of children's statements, such as emotional factors of children and parents and trauma-related variables, in Korean child sex abuse victims. Methods: We enrolled 214…

  9. Exploring Factors Influencing Acceptance and Use of Video Digital Libraries

    ERIC Educational Resources Information Center

    Ju, Boryung; Albertson, Dan

    2018-01-01

    Introduction: This study examines the effects of certain key factors on users' intention to ultimately adopt and use video digital libraries for facilitating their information needs. The individual factors identified for this study, based on their given potential to influence use and acceptance of video digital libraries, were categorised for data…

  10. Biological Impact of Senescence Induction in Prostate Cancer

    DTIC Science & Technology

    2010-01-01

    with decreasing compound concentrations. Data showing chlorhexidine, bithionol, cytarabine and crassin acetate effectively inhibited proliferation...senescence with 25 nM doxorubicin were included as a positive control. Of the candi- date compounds, methotrexate, cytarabine , chlorhexidine, and IC261...then normalized to expression in untreated cells. Candidate compounds: methotrexate (MET), chlorhexadine (CHL), crassin acetate (CRA), cytarabine

  11. Prenatal environmental factors influencing IgE levels, atopy and early asthma.

    PubMed

    Peters, Junenette L; Boynton-Jarrett, Renée; Sandel, Megan

    2013-04-01

    There is increasing evidence that the prenatal window represents a critical period in which the developing immune system may be primed toward an allergic phenotype. Studies have investigated the role of a number of maternal environmental exposures on subsequent allergic disorders in the offspring. We summarize findings from recent studies on prenatal environmental factors influencing IgE levels, atopy, and early asthma. A building literature supports the influence of maternal exposure to environmental pollutants, such as allergens, traffic-related air pollution, tobacco smoke, and organochlorine compounds and social factors on allergic outcomes. More novel associations have been investigated, such as the effect of prenatal exposures to phthalates, bisphenol A, and magnetic fields. There is also rising interest in epigenetics as a pathway of action by which maternal exposure affect immune health. Emerging research highlights the challenges of investigating in-utero exposures and of relating exposures to such a heterogeneous and complex outcome as allergic disease. Further research is needed on the mechanisms by which prenatal exposure influences allergic response in childhood and how postnatal, familial and social factors, and sex can modify disease outcomes. Epigenetics is a promising new frontier, and likely one of several explanatory factors.

  12. Factors influencing aircraft ground handling performance

    NASA Technical Reports Server (NTRS)

    Yager, T. J.

    1983-01-01

    Problems associated with aircraft ground handling operations on wet runways are discussed and major factors which influence tire/runway braking and cornering traction capability are identified including runway characteristics, tire hydroplaning, brake system anomalies, and pilot inputs. Research results from tests with instrumented ground vehicles and aircraft, and aircraft wet runway accident investigation are summarized to indicate the effects of different aircraft, tire, and runway parameters. Several promising means are described for improving tire/runway water drainage capability, brake system efficiency, and pilot training to help optimize aircraft traction performance on wet runways.

  13. An Analysis of Selected Factors Influencing Enrollment Patterns.

    ERIC Educational Resources Information Center

    Heck, James

    This report presents an analysis of factors influencing enrollment patterns at Lake City Community College (LCCC; Florida) and recommends ways to increase enrollments at the college. Section I reviews the methods of collecting data for the report, which included interviews with key college personnel, an examination of social indicators such as…

  14. Factors Influencing the Readability of Student-Generated Texts.

    ERIC Educational Resources Information Center

    Allen, JoBeth

    An investigation examined student-generated texts in terms of both traditional and more theoretically valid readability to determine what factors influence comprehension when children read their own, peer, and adult-written texts. Seventy dictated stories created in an earlier study, along with 4 first-grade level stories from the "Reader's…

  15. Factors Influencing Teachers' Engagement in Informal Learning Activities

    ERIC Educational Resources Information Center

    Lohman, Margaret C.

    2006-01-01

    Purpose: The purpose of this study is to examine factors influencing the engagement of public school teachers in informal learning activities. Design/methodology/approach: This study used a survey research design. Findings: Analysis of the data found that teachers rely to a greater degree on interactive than on independent informal learning…

  16. What Factors Influence Vietnamese Students' Choice of University?

    ERIC Educational Resources Information Center

    Dao, Mai Thi Ngoc; Thorpe, Anthony

    2015-01-01

    Purpose: The purpose of this paper is to report the factors that influence Vietnamese students' choice of university in a little researched context where the effects of globalization and education reform are changing higher education. Design/methodology/approach: A quantitative survey was completed by 1,124 current or recently completed university…

  17. Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia.

    PubMed

    Yan, Han; Wen, Lu; Tan, Dan; Xie, Pan; Pang, Feng-Mei; Zhou, Hong-Hao; Zhang, Wei; Liu, Zhao-Qian; Tang, Jie; Li, Xi; Chen, Xiao-Ping

    2017-01-03

    The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10-4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.

  18. Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

    PubMed Central

    Yan, Han; Wen, Lu; Tan, Dan; Xie, Pan; Pang, Feng-mei; Zhou, Hong-hao; Zhang, Wei; Liu, Zhao-qian; Tang, Jie; Li, Xi; Chen, Xiao-ping

    2017-01-01

    The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10−4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis. PMID:27903973

  19. Factors influencing enrollment of African Americans in the Look AHEAD trial

    USDA-ARS?s Scientific Manuscript database

    Many factors have been identified that influence the recruitment of African Americans into clinical trials; however, the influence of eligibility criteria may not be widely appreciated. We used the experience from the Look AHEAD (Action for Health in Diabetes) trial screening process to examine the ...

  20. Factors influencing primary health care professionals' physical activity promotion behaviors: a systematic review.

    PubMed

    Huijg, Johanna M; Gebhardt, Winifred A; Verheijden, Marieke W; van der Zouwe, Nicolette; de Vries, Juriena D; Middelkoop, Barend J C; Crone, Mathilde R

    2015-02-01

    Despite the promising findings related to the efficacy of interventions aimed at promoting physical activity (PA) in primary health care (PHC), the translation of these interventions to PHC practice does not always happen as desired. To help understand why efficacious PHC-based PA interventions are not effectively translated to practice, this study systematically reviewed the literature on factors influencing PHC professionals' PA promotion practices. Literature searches were conducted in Web of Science, PubMed, and PsycINFO for peer-reviewed articles published in English from 1990 onwards. Studies were included that met the following criteria: (1) involving PHC-based PA interventions, and (2) reporting factors influencing PHC professionals' PA promotion behaviors. Two researchers independently screened studies and extracted data. A narrative synthesis using thematic analysis was conducted to identify factors. Of the 4,469 identified articles, 59 were included in the review. Factors were identified by qualitative methods, barrier/facilitator ratings, and the examination of the relationship between factors and PA promotion, and the effectiveness of introduction strategies. Many factors related to the development, delivery, and effects of the innovation, the sociopolitical and organizational culture, resources, and support, patient and PHC professional characteristics, and innovation strategies were identified as potential influences on PHC professionals' PA promotion practices. However, the lack of evidence on the relationship between factors and PA promotion indicated insufficient evidence on PA promotion determinants. This extensive overview of potential factors can inform intervention developers and implementers on which factors may play a role when introducing PA interventions in PHC. Future research should further investigate relationships between factors and PA promotion, which should be guided by qualitative in-depth knowledge on influencing factors.

  1. Factors Influencing Technology Planning in Developing Countries: A Literature Review

    ERIC Educational Resources Information Center

    Keengwe, Jared; Malapile, Sandy

    2014-01-01

    This article is a literature review concerning the factors that play an important role in the development of educational technology plans in the educational system of developing countries (DCs). Largely, the technology plans are influenced by factors that emanates from within the country (internal) and those outside of their borders (external).…

  2. Factors Influencing Psychological Help Seeking in Adults: A Qualitative Study

    ERIC Educational Resources Information Center

    Topkaya, Nursel

    2015-01-01

    The aim of the current research is to identify which factors, and in what direction these factors influence adults' decisions to seek psychological help for their personal problems. The research was designed as a phenomenology model; the data was gathered through the semi-structured interview technique, which is mostly used in qualitative research…

  3. Factors influencing micronutrient bioavailability in biofortified crops.

    PubMed

    Bechoff, Aurélie; Dhuique-Mayer, Claudie

    2017-02-01

    Dietary and human factors have been found to be the major factors influencing the bioavailability of micronutrients, such as provitamin A carotenoid (pVAC), iron, and zinc, in biofortified crops. Dietary factors are related to food matrix structure and composition. Processing can improve pVAC bioavailability by disrupting the food matrix but can also result in carotenoid losses. By degrading antinutrients, such as phytate, processing can also enhance mineral bioavailability. In in vivo interventions, biofortified crops have been shown to be overall efficacious in reducing micronutrient deficiency, with bioconversion factors varying between 2.3:1 and 10.4:1 for trans-β-carotene and amounts of iron and zinc absorbed varying between 0.7 and 1.1 mg/day and 1.1 and 2.1 mg/day, respectively. Micronutrient bioavailability was dependent on the crop type and the presence of fat for pVACs and on antinutrients for minerals. In addition to dietary factors, human factors, such as inflammation and disease, can affect micronutrient status. Understanding the interactions between micronutrients is also essential, for example, the synergic effect of iron and pVACs or the competitive effect of iron and zinc. Future efficacy trials should consider human status and genetic polymorphisms linked to interindividual variations. © 2016 New York Academy of Sciences.

  4. [Factors influencing self-perception of overweight people].

    PubMed

    Makara-Studzińska, Marta; Podstawka, Danuta; Goclon, Karolina

    2013-11-01

    Shaping of self-perception is among others influenced by physical, interpersonal, emotional, and cultural factors. In self-perception of overweight people an important role is played by interpersonal factors, which include the opinions of others and the relationship with the surrounding. The evaluation of the body image is also affect by sociocultural factors including the media, which create an unrealistic and impossible to achieve ideal of beauty. Contemporary ideal of beauty, where a slim figure is dominant, more frequently contributes to the occurrence of discrimination and stigmatization of overweight people. This phenomenon causes negative self-perception leading to the occurrence of such emotional problems as low self-esteem, lack of confidence, depression and anxiety disorders. Overweight children and adolescents are also frequently stigmatized and discriminated because of their body weight, which results in the development of a negative body image that may lead to low self-esteem and symptoms of depression.

  5. Factors influencing career decisions in internal medicine.

    PubMed

    Macdonald, C; Cawood, T

    2012-08-01

    Numerous factors influence career decisions for internal medicine trainees and Fellows. There is a perception that a greater emphasis is placed on work-family balance by younger physicians. To determine the characteristics of the modern internal medicine workforce and ascertain whether job flexibility is important to career decision-making. We hypothesised that factors which reflect flexibility would be highly influential in decision-making, especially for women and those with young children. A questionnaire was mailed to 250 New Zealand internal medicine trainees and Fellows. It focused on factors, including job flexibility, interest and collegial support, and included demographic details which were primarily aimed at ascertaining family responsibilities. Response rate was 54%. The majority of female physicians are the main person responsible for their children (62%), and the majority of their partners work full-time (80%). This contrasts with male physicians, of whom only 4% are the main person responsible for their children. Flexibility was found to be more influential in women, those with young children, trainees and those working in outpatient-based subspecialties. However, contrary to our original hypothesis, flexibility was not reported to be highly influential in any group, with career choice being most influenced by interest and enjoyment, intellectual challenge and variety within the job. It is hoped that results will inform employers and those involved with training to enable them to better cater for the needs of the workforce and also encourage trainees to consider future family commitments when making career decisions. © 2012 The Authors. Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

  6. [Analysis on influencing factor of the complications of percutaneous dilational tracheotomy].

    PubMed

    Zhai, Xiang; Zhang, Jinling; Hang, Wei; Wang, Ming; Shi, Zhan; Mi, Yue; Hu, Yunlei; Liu, Gang

    2015-01-01

    To Analyze the influence factors on the complications of percutaneous dilational tracheotomy. Between August 2008 and February 2014, there were 3 450 patients with the indications of tracheotomy accepted percutaneous dilational tracheostomy, mainly using percutaneous dilational and percutaneous guide wire forceps in these cases. Statistical analysis was performed by SPSS 19.0 software on postoperative complications, the possible influence factors including age, gender, etiology, preoperative hypoxia, obesity, preoperative pulmonary infection, state of consciousness, operation method, operation doctor and whether with tracheal intubation. Among 3 450 patients, there were 164 cases with intraoperative or postoperative complications, including postoperative bleeding in 74 cases (2.14%), subcutaneous emphysema in 54 cases (1.57%), wound infection in 16 cases (0.46%), pneumothorax in 6 cases (0.17%), mediastinal emphysema in 5 cases (0.14%), operation failed and change to conventional incision in 4 cases (0.12%), tracheoesophageal fistula in 2 cases (0.06%), death in 3 cases(0.09%).Obesity, etiology, preoperative hypoxia, preoperative pulmonary infection, state of consciousness and operation method were the main influence factors, with significant statistical difference (χ(2) value was 0.010, 0.000, 0.002, 0.000, 0.000, 0.000, all P < 0.05). Gender, age, operation doctor and whether there was the endotracheal intubation were not the main influence factors. There was no significant statistical difference (P > 0.05). Although percutaneous dilational tracheostomy is safe, but the complications can also happen. In order to reduce the complications, it is need to pay attention to the factors of obesity, etiology, preoperative hypoxia, preoperative pulmonary infection, state of consciousness and operation method.

  7. The influencing factors on place attachment in neighborhood of Kampung Melayu

    NASA Astrophysics Data System (ADS)

    Lestari, W. M.; Sumabrata, J.

    2018-03-01

    Place attachment on neighborhood differs according to place characteristics and person characteristics. By dividing the research area of Kelurahan Kampung Melayu into flood area and non-flood area, this research aims at analyzing place attachment on neighborhood and analyzing factors influencing the place attachment. This research using quantitative approach using Structural Equation Modeling (SEM). Self-administered questionnaires using likert scale were distributed randomly to 400 residents. Result of the research shows that residents tend to have place attachment to their neighborhood. Factors influencing place attachment on residents born in the neighborhood with length of stay 10 years or longer and having house are family factor for residents living in non-flood area and physical factor as well as social factor for residents in flood area. This research concludes that place attachment on neighborhood is formed because dimension of place is interpreted not merely physically but also socially, namely the existence of family ties and social relationship with people in the neighborhood.

  8. Factors Influencing Learning Environments in an Integrated Experiential Program

    NASA Astrophysics Data System (ADS)

    Koci, Peter

    The research conducted for this dissertation examined the learning environment of a specific high school program that delivered the explicit curriculum through an integrated experiential manner, which utilized field and outdoor experiences. The program ran over one semester (five months) and it integrated the grade 10 British Columbian curriculum in five subjects. A mixed methods approach was employed to identify the students' perceptions and provide richer descriptions of their experiences related to their unique learning environment. Quantitative instruments were used to assess changes in students' perspectives of their learning environment, as well as other supporting factors including students' mindfulness, and behaviours towards the environment. Qualitative data collection included observations, open-ended questions, and impromptu interviews with the teacher. The qualitative data describe the factors and processes that influenced the learning environment and give a richer, deeper interpretation which complements the quantitative findings. The research results showed positive scores on all the quantitative measures conducted, and the qualitative data provided further insight into descriptions of learning environment constructs that the students perceived as most important. A major finding was that the group cohesion measure was perceived by students as the most important attribute of their preferred learning environment. A flow chart was developed to help the researcher conceptualize how the learning environment, learning process, and outcomes relate to one another in the studied program. This research attempts to explain through the consideration of this case study: how learning environments can influence behavioural change and how an interconnectedness among several factors in the learning process is influenced by the type of learning environment facilitated. Considerably more research is needed in this area to understand fully the complexity learning

  9. Factors influencing perceived sustainability of Dutch community health programs.

    PubMed

    Vermeer, A J M; Van Assema, P; Hesdahl, B; Harting, J; De Vries, N K

    2015-09-01

    We assessed the perceived sustainability of community health programs organized by local intersectoral coalitions, as well as the factors that collaborating partners think might influence sustainability. Semi-structured interviews were conducted among 31 collaborating partners of 5 community health programs in deprived neighborhoods in the southern part of the Netherlands. The interview guide was based on a conceptual framework that includes factors related to the context, the leading organization, leadership, the coalition, collaborating partners, interventions and outcomes. Interviews were recorded, transcribed and content analyzed using NVivo 8.0. Participants in each of the programs varied in their perceptions of the sustainability of the program, but those people collaborating in pre-existing neighborhood structures expressed relatively high faith in their continuation. The participating citizens in particular believed that these structures would continue to address the health of the community in the future. We found factors from all categories of the conceptual framework that were perceived to influence sustainability. The program leaders appeared to be crucial to the programs, as they were frequently mentioned in close interaction with other factors. Program leaders should use a motivating and supportive leadership style and should act as 'program champions'. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Personal and situational factors influencing coaches' perceptions of stress.

    PubMed

    Knight, Camilla J; Reade, Ian L; Selzler, Anne-Marie; Rodgers, Wendy M

    2013-01-01

    Coaching has been recognised as a demanding occupation, associated with a range of stressors. The extent to which coaches perceive stress is likely to be influenced by various personal and situational factors. The purpose of this study was to identify coaches' levels of perceived stress and examine the personal and situational factors that may influence coaches' perceptions of stress. In total, 502 coaches working with university, college, Canada Games, and/or nationally identified athletes completed this study. Coaches completed an online survey, which included questions regarding demographics, work/job-related considerations, and aspects relating to their contract. Coaches also completed the Perceived Stress Scale (Cohen, Kamarck, & Mermelstein, 1983). Overall coaches indicated slightly below average levels of perceived stress (M = 15.13 out of 40) compared with norm-values (Cohen & Janicki-Deverts, 2012). Demographic factors, job-related characteristics, and certain aspects of their contract were associated with coaches' perceptions of stress. In particular, unclear expectations, long-working hours (>40), lack of agreed evaluation criteria, higher salaries, and a lack of social support were related to higher perceptions of stress. As such, the findings of the current study indicate that a reduction in perceived stress is likely to be achieved through a multifaceted approach that addresses multiple factors associated with coaching.

  11. Drugs Approved for Non-Hodgkin Lymphoma

    MedlinePlus

    ... Vedotin Calquence (Acalabrutinib) Carmustine Chlorambucil Copanlisib Hydrochloride Cyclophosphamide Cytarabine Liposome Denileukin Diftitox DepoCyt (Cytarabine Liposome) Dexamethasone Doxorubicin ...

  12. Factors that Influence Students' Decision to Dropout of Online Courses

    ERIC Educational Resources Information Center

    Willging, Pedro A.; Johnson, Scott D.

    2009-01-01

    Although there are many reasons why students dropout of college courses, those reasons may be unique for students who are enrolled in an online program. Issues of isolation, disconnectedness, and technological problems may be factors that influence a student to leave a course. To understand these factors, an online survey was developed to collect…

  13. Factors Influencing Female Registered Nurses' Work Behavior

    PubMed Central

    Brewer, Carol S; Kovner, Christine T; Wu, Yow-Wu; Greene, William; Liu, Yu; Reimers, Cordelia W

    2006-01-01

    Objective To analyze factors that are related to whether registered nurses (RNs) work (WK) or do not work (NW) in nursing; and if the RN works, whether she works full- (FT) or part-time (PT). Data Sources Secondary data from National Sample Survey of Registered Nurses 2000 (NSSRN), the InterStudy Competitive Edge Part III Regional Market Analysis (2001), and the Area Resource File (2002). Study Design Using a cross-sectional design we tested the relationship between WK or NW and FT or PT; and demographic, job-related, and metropolitan statistical area (MSA)-level variables. Data Collection/Extraction Methods We combined the data sources noted above to produce the analytic sample of 25,471 female RNs. Principal Findings Working in nursing is not independent of working FT or PT. Age (55 and older), other family income, and prior other work experience in health care are negatively related to working as an RN. The wage is not related to working as an RN, but negatively influences FT work. Age, children, minority status, student status, employment status, other income, and some job settings have a negative impact on working FT. Previous health care work has a positive effect on whether married RNs worked. Married RNs who are more dissatisfied are less likely to work FT. A greater number of market-level factors influence FT/PT than WK/NW behavior. Conclusions An important contribution of this study is demonstrating that MSA-level variables influence RN work behavior. The market environment seems to have little effect on whether a nurse works, but is influential on how much the nurse works, and has differential effects on married versus single nurses. PMID:16704517

  14. Factors Influencing the Reliability of the Glasgow Coma Scale: A Systematic Review.

    PubMed

    Reith, Florence Cm; Synnot, Anneliese; van den Brande, Ruben; Gruen, Russell L; Maas, Andrew Ir

    2017-06-01

    The Glasgow Coma Scale (GCS) characterizes patients with diminished consciousness. In a recent systematic review, we found overall adequate reliability across different clinical settings, but reliability estimates varied considerably between studies, and methodological quality of studies was overall poor. Identifying and understanding factors that can affect its reliability is important, in order to promote high standards for clinical use of the GCS. The aim of this systematic review was to identify factors that influence reliability and to provide an evidence base for promoting consistent and reliable application of the GCS. A comprehensive literature search was undertaken in MEDLINE, EMBASE, and CINAHL from 1974 to July 2016. Studies assessing the reliability of the GCS in adults or describing any factor that influences reliability were included. Two reviewers independently screened citations, selected full texts, and undertook data extraction and critical appraisal. Methodological quality of studies was evaluated with the consensus-based standards for the selection of health measurement instruments checklist. Data were synthesized narratively and presented in tables. Forty-one studies were included for analysis. Factors identified that may influence reliability are education and training, the level of consciousness, and type of stimuli used. Conflicting results were found for experience of the observer, the pathology causing the reduced consciousness, and intubation/sedation. No clear influence was found for the professional background of observers. Reliability of the GCS is influenced by multiple factors and as such is context dependent. This review points to the potential for improvement from training and education and standardization of assessment methods, for which recommendations are presented. Copyright © 2017 by the Congress of Neurological Surgeons.

  15. Succesful Lean Manufacturing Implementation: Internal Key Influencing Factors

    NASA Astrophysics Data System (ADS)

    Virginia, Iuga; Claudiu, Kifor

    2015-09-01

    Manufacturing sectors and companies all over the world are successfully implementing lean principles within their processes. Nowadays, lean has become an indispensable part of global players. Companies worldwide need to be aware of multiple factors which weigh heavily on the success or failure of lean implementation. This paper focuses on giving a brief and structured overview over the fundamental organizational factors which play a substantial role for the lean manufacturing (LM) implementation process. The study below focuses on internal factors which are indispensable for a successful LM implementation within organizations. It is imperative that these internal factors are known, recognized and taken into consideration during the whole LM implementation process. Ignoring their influence on the process's implementation may lead to endangering the expected results or to making the process more difficult which could result in much higher human resource consumption.

  16. FACTORS INFLUENCING CHOICE OF ORAL HYGIENE PRODUCTS BY DENTAL PATIENTS IN A NIGERIAN TEACHING HOSPITAL.

    PubMed

    Opeodu, O I; Gbadebo, S O

    2017-06-01

    Several factors, such as cost, branding, packaging and family influence, had been implicated as influencing the choice of toothpastes and toothbrushes by individuals. Media advertisement is also considered a very strong factor influencing consumer's choice. To assess the extent to which some factors influenced the choice of toothpastes and toothbrushes among dental patients in a Nigerian teaching hospital. Two-hundred and two patients were interviewed on factors that influenced their choice of toothbrush and toothpaste. Some of the factors considered include the cost, packaging, brand, media advertisement and their previous experience. Factors that affected choice of toothbrush by respondents included texture (89.6%), brand (62.9%), previous experience (64.4%) and for toothpaste, fluoride content (62.4%), previous experience (69.3%), and advice by a dentist (55.0%). Media advertisement was the least influential in their choice of toothpaste (29.2%) and toothbrush (24.3%). Consideration for fluoride was a stronger factor than herbal contents in the choice of toothpaste (P<0.001). Previous experience seems to be a very strong factor in the choice of both the toothbrush and toothpaste in this study, which suggest that for as long as the respondents are satisfied with a particular product, they will stick to it.

  17. FACTORS INFLUENCING CHOICE OF ORAL HYGIENE PRODUCTS BY DENTAL PATIENTS IN A NIGERIAN TEACHING HOSPITAL

    PubMed Central

    Opeodu, O.I.; Gbadebo, S.O.

    2017-01-01

    Background: Several factors, such as cost, branding, packaging and family influence, had been implicated as influencing the choice of toothpastes and toothbrushes by individuals. Media advertisement is also considered a very strong factor influencing consumer's choice. Aim: To assess the extent to which some factors influenced the choice of toothpastes and toothbrushes among dental patients in a Nigerian teaching hospital. Materials and methods: Two-hundred and two patients were interviewed on factors that influenced their choice of toothbrush and toothpaste. Some of the factors considered include the cost, packaging, brand, media advertisement and their previous experience. Results: Factors that affected choice of toothbrush by respondents included texture (89.6%), brand (62.9%), previous experience (64.4%) and for toothpaste, fluoride content (62.4%), previous experience (69.3%), and advice by a dentist (55.0%). Media advertisement was the least influential in their choice of toothpaste (29.2%) and toothbrush (24.3%). Consideration for fluoride was a stronger factor than herbal contents in the choice of toothpaste (P<0.001) Conclusion: Previous experience seems to be a very strong factor in the choice of both the toothbrush and toothpaste in this study, which suggest that for as long as the respondents are satisfied with a particular product, they will stick to it. PMID:28970772

  18. Factors that influencing the usage of global distribution system

    NASA Astrophysics Data System (ADS)

    Budiasa, I. M.; Suparta, I. K.; Nadra, N. M.

    2018-01-01

    The advancement of Tourism is supported by Information and Communication Technology (ICT) innovation and changes. The use of GDS (Global Distribution System) i.e. Amadeus, Galileo, Sabre, and Worldspan in the tourism industry can increase the availability, frequency and speed of communication among the companies in providing services to potential tourists. This research is to investigate the factors that influence the actual use of GDS in the tourism industry especially travel agents, airlines and hotels in Bali. This research employed a mixed method of quantitative and qualitative approaches. Field surveys were conducted and 80 valid questionnaires were received and analyzed by using SPSS 17.0; descriptive, correlation, factor analysis and regression tests were conducted. The variables used are Perceived Ease of Use and Perceived Usefulness (Technology Acceptance Model); Awareness, Perceived Risk and Communication Channels are examined. This research revealed that Perceived Ease of Use, Perceived Usefulness, Awareness, and Communication Channels influence the Behavioural intention to use GDS, whereas Perceived Risk were found not significant influence the use of GDS. These findings enable travel agent, airline and hotel companies to make provision decision with respect to the actual use of GDS.

  19. Influence of psychological factors on the acceptance of complete dentures.

    PubMed

    al Quran, F; Clifford, T; Cooper, C; Lamey, P J

    2001-07-01

    To assess the influence of psychological factors on the acceptance of complete dentures in a population wearing dentures judged to be clinically satisfactory. Subjects were asked to complete personality profiles and also to rate their dentures using a denture satisfaction questionnaire. The survey was conducted in the prosthetics clinic of a teaching hospital. Patients were selected from those who had new complete dentures constructed in the department within the previous two years. The personality inventory was a self-administered questionnaire comprising 240 items covering the five domains of personality. Denture satisfaction was scored on a nine item scale with four Likert type responses to each. A group of 16% consistently complained about their dentures. Statistical analysis showed that personality factors especially Neuroticism had a significant relationship with denture satisfaction. Psychological factors significantly influence denture satisfaction and profiles may provide useful in predicting potential difficult denture wearers.

  20. Implementing complex innovations: factors influencing middle manager support.

    PubMed

    Chuang, Emmeline; Jason, Kendra; Morgan, Jennifer Craft

    2011-01-01

    Middle manager resistance is often described as a major challenge for upper-level administrators seeking to implement complex innovations such as evidence-based protocols or new skills training. However, factors influencing middle manager support for innovation implementation are currently understudied in the U.S. health care literature. This article examined the factors that influence middle managers' support for and participation in the implementation of work-based learning, a complex innovation adopted by health care organizations to improve the jobs, educational pathways, skills, and/or credentials of their frontline workers. We conducted semistructured interviews and focus groups with 92 middle managers in 17 health care organizations. Questions focused on understanding middle managers' support for work-based learning as a complex innovation, facilitators and barriers to the implementation process, and the systems changes needed to support the implementation of this innovation. Factors that emerged as influential to middle manager support were similar to those found in broader models of innovation implementation within the health care literature. However, our findings extend previous research by developing an understanding about how middle managers perceived these constructs and by identifying specific strategies for how to influence middle manager support for the innovation implementation process. These findings were generally consistent across different types of health care organizations. Study findings suggest that middle manager support was highest when managers felt the innovation fit their workplace needs and priorities and when they had more discretion and control over how it was implemented. Leaders seeking to implement innovations should consider the interplay between middle managers' control and discretion, their narrow focus on the performance of their own departments or units, and the dedication of staff and other resources for empowering their

  1. Key Factors that Influence Recruiting Young Chinese Students

    ERIC Educational Resources Information Center

    Wang, Zhenmin

    2007-01-01

    The discussion in this paper is based on the assumption that international education is equated to recruiting and educating international students, even though its true concept goes far beyond this narrow understanding. The purpose of this research is to look at the key factors that influence recruiting young Chinese students, and make sure all…

  2. High Enrollment Course Success Factors in Virtual School: Factors Influencing Student Academic Achievement

    ERIC Educational Resources Information Center

    Liu, Feng; Cavanaugh, Cathy

    2011-01-01

    This paper describes a study of success factors in high enrollment courses in a K-12 virtual school learning environment. The influence of variables: time student spent in the learning management system (LMS), number of times logged into the LMS, teacher comment, participation in free or reduced lunch programs, student status in the virtual school…

  3. Factors Influencing the Career Planning and Development of University Students in Jordan

    ERIC Educational Resources Information Center

    Khasawneh, Samer

    2010-01-01

    The purpose of this study was to translate and validate an Arabic version of the career influence inventory for use in Jordan. The study also investigated perceptions of university students of the influential factors that have influenced their career planning and development. The validated career influence inventory was administered to 558…

  4. Personal and social factors that influence pro-environmental concern and behaviour: a review.

    PubMed

    Gifford, Robert; Nilsson, Andreas

    2014-06-01

    We review the personal and social influences on pro-environmental concern and behaviour, with an emphasis on recent research. The number of these influences suggests that understanding pro-environmental concern and behaviour is far more complex than previously thought. The influences are grouped into 18 personal and social factors. The personal factors include childhood experience, knowledge and education, personality and self-construal, sense of control, values, political and world views, goals, felt responsibility, cognitive biases, place attachment, age, gender and chosen activities. The social factors include religion, urban-rural differences, norms, social class, proximity to problematic environmental sites and cultural and ethnic variations We also recognize that pro-environmental behaviour often is undertaken based on none of the above influences, but because individuals have non-environmental goals such as to save money or to improve their health. Finally, environmental outcomes that are a result of these influences undoubtedly are determined by combinations of the 18 categories. Therefore, a primary goal of researchers now should be to learn more about how these many influences moderate and mediate one another to determine pro-environmental behaviour. © 2014 International Union of Psychological Science.

  5. Factors that Influence RF Breakdown in Antenna Systems

    NASA Astrophysics Data System (ADS)

    Caughman, J. B. O.; Baity, F. W.; Rasmussen, D. A.; Aghazarian, M.; Castano Giraldo, C. H.; Ruzic, David

    2007-11-01

    One of the main power-limiting factors in antenna systems is the maximum voltage that the antenna or vacuum transmission line can sustain before breaking down. The factors that influence RF breakdown are being studied in a resonant 1/4-wavelength section of vacuum transmission line terminated with an open circuit electrode structure. Breakdown can be initiated via electron emission by high electric fields and by plasma formation in the structure, depending on the gas pressure. Recent experiments have shown that a 1 kG magnetic field can influence plasma formation at pressures as low as 8x10-5 Torr at moderate voltage levels (<5 kV). Ultraviolet light, with energies near the work function of the electrode material, can induce a multipactor discharge and limit power transmission. Details of these experimental results, including the effect of electrode materials (Ni and Cu), will be presented. Oak Ridge National Laboratory is managed by UT-Battelle, LLC, for the U.S. Dept. of Energy under contract DE-AC05-00OR22725. Work supported by USDOE with grant DE-FG02-04ER54765

  6. Preparation and the influencing factors of timozolomide liposomes.

    PubMed

    Kong, Bin; Sun, Yong; Li, Yongjian; Hu, Dejian

    2009-01-01

    To prepare timozolomide liposomes for administration through nasal mucous membrane, we studied the factors of the preparation of the liposomes. The timozolomide liposomes were prepared by the ammonium sulphate gradient method; electroscopy and laser particle analyzer were utilized to determine the conformation, size and distribution of timozolomide liposomes; high performance liquid chromatography (HPLC) was applied to determine the entrapping efficiency of timozolomide liposomes; then we studied the influences of the concentration of ammonium sulphate solution, temperature, and the drug-to-lipid ratio on the entrapping efficiency. The average size of timozolomide liposomes was 185 nm; the entrapping efficiency was 90.3%. The entrapping efficiency was enhanced with the increasing of the concentration of ammonium sulphate solution and the rising of temperature, and decreased with the increasing of the drug-to-lipid ratio. The timozolomide liposomes with high entrapping efficiency, small and even particle sizes could be prepared by the simple and convenient ammonium sulphate gradient method. The primary influencing factors on the entrapping efficiency of timozolomide liposomes were the concentration of ammonium sulphate solution, the temperature, and the drug-to-lipid ratio.

  7. A Phenomenological Study: The Influence of Noncognitive Factors on Academically Unprepared College Students

    ERIC Educational Resources Information Center

    Thom, Danny Moire

    2012-01-01

    This phenomenological research explored the influence of noncognitive factors in four areas: early educational factors, personal factors, affective factors, and noncognitive skill factors to understand the phenomenon of college students' academic underpreparedness. Findings related to textual categories indicated personal factors such as a…

  8. Factors that influence nurses' job satisfaction.

    PubMed

    Ma, Chen-Chung; Samuels, Michael E; Alexander, Judith W

    2003-05-01

    To examine factors affecting the job satisfaction of registered nurses (RNs). A growing recognition of job dissatisfaction among RNs in South Carolina hospitals has contributed to current problems with recruitment and retention. If administrators identify factors influencing RNs' job satisfaction in hospitals and implement strategies to address these factors, RN turnover rates will decrease and recruiting and retention rates will increase. A cross-sectional study of secondary data was designed to identify the individual, work, and geographic factors that impact nursing job satisfaction at the state level. A 27-question self-administered survey was sent to 17,500 RNs in South Carolina with postage-paid envelopes for their responses. Surveys from 3472 nurses were completed anonymously. Univariate statistics were used to describe the study sample. One-way and multivariable Analysis of Variance were used to determine which variables contributed the most to job satisfaction. For about two thirds of the RNs, job satisfaction remained the same or had lessened over the past 2 years. In addition, statistically significant differences were found between job satisfaction and years of service, job position, hospital retirement plan, and geographic area. The findings have implications for nurse managers and hospital administrators for planning and implementing effective health policies that will meet the unique needs of their staffs and organizations. Such research is particularly relevant in this difficult time of nursing shortages throughout the healthcare industry.

  9. Factors Influencing Students' Achievement in Form 5 Islamic Studies Subject

    ERIC Educational Resources Information Center

    bin Che Noh, Mohd Aderi; Omar, Noraini binti; bin Kasan, Hasnan

    2013-01-01

    This study is aimed at analyzing the factors influencing the achievements of students in the subject of Islamic Studies for Form 5 SPM (KBSM) in schools in the area of Samarahan, Sarawak. The factors analysed is attitude and interest. This is a survey based study and data was compiled from the survey forms which had the topic "Factors…

  10. Weaning from mechanical ventilation: factors that influence intensive care nurses' decision-making.

    PubMed

    Tingsvik, Catarina; Johansson, Karin; Mårtensson, Jan

    2015-01-01

    The aim of the study was to describe the factors that influence intensive care nurses' decision-making when weaning patients from mechanical ventilation. Patients with failing vital function may require respiratory support. Weaning from mechanical ventilation is a process in which the intensive care nurse participates in both planning and implementation. A qualitative approach was used. The data were collected by means of semi-structured interviews with 22 intensive care nurses. The interviews were transcribed and analysed using qualitative content analysis. One theme emerged: 'A complex nursing situation where the patient receives attention and which is influenced by the current care culture'. There was consensus that the overall assessment of the patient made by the intensive care nurse was the main factor that influenced the decision-making process. This assessment was a continuous process consisting of three factors: the patient's perspective as well as her/his physical and mental state. On the other hand, there was a lack of consensus about what other factors influenced the decision-making process. These factors included the care culture constituted by the characteristics of the team, the intensive care nurses' professional skills, personalities and ability to be present. The individual overall assessment of the patient enabled nursing care from a holistic perspective. Furthermore, the weaning process can be more effective and potential suffering reduced by creating awareness of the care culture's impact on the decision-making process. © 2014 British Association of Critical Care Nurses.

  11. A proposed model of factors influencing hydrogen fuel cell vehicle acceptance

    NASA Astrophysics Data System (ADS)

    Imanina, N. H. Noor; Kwe Lu, Tan; Fadhilah, A. R.

    2016-03-01

    Issues such as environmental problem and energy insecurity keep worsening as a result of energy use from household to huge industries including automotive industry. Recently, a new type of zero emission vehicle, hydrogen fuel cell vehicle (HFCV) has received attention. Although there are argues on the feasibility of hydrogen as the future fuel, there is another important issue, which is the acceptance of HFCV. The study of technology acceptance in the early stage is a vital key for a successful introduction and penetration of a technology. This paper proposes a model of factors influencing green vehicle acceptance, specifically HFCV. This model is built base on two technology acceptance theories and other empirical studies of vehicle acceptance. It aims to provide a base for finding the key factors influencing new sustainable energy fuelled vehicle, HFCV acceptance which is achieved by explaining intention to accept HFCV. Intention is influenced by attitude, subjective norm and perceived behavioural control from Theory of Planned Behaviour and personal norm from Norm Activation Theory. In the framework, attitude is influenced by perceptions of benefits and risks, and social trust. Perceived behavioural control is influenced by government interventions. Personal norm is influenced by outcome efficacy and problem awareness.

  12. Factors influencing restaurant worker perception of floor slipperiness.

    PubMed

    Courtney, Theodore K; Huang, Yueng-Hsiang; Verma, Santosh K; Chang, Wen-Ruey; Li, Kai Way; Filiaggi, Alfred J

    2006-11-01

    Falls are responsible for a substantial injury burden in the global workplace. Restaurant environments are particularly challenged by slips, trips, and falls. This study explored those factors that could influence workers' self-reports of slipperiness in U.S. fast-food restaurants. One hundred and twenty-six workers employed in 10 fast-food restaurants in the northeastern United States participated in the study representing a study-wide response rate of 87.5%. Participants' ratings of floor slipperiness and occupational slip history within the past 4 weeks were collected through written questionnaire. Additional factors collected by questionnaire included age, gender, shift length, and shoe type. Shoe condition (wear) and shoe contamination were visually assessed by the investigators. Floor friction was also measured. Lower restaurant mean coefficient of friction and the presence of contamination on workers' shoe soles were environmental factors significantly associated with workers reporting more slippery conditions. A recent workplace history of slipping with or without a subsequent fall was also significantly associated with workers reporting more slippery conditions. Workers over the age of 45 reported conditions to be significantly less slippery than younger workers. The results suggest that worker ratings of slipperiness are influenced not only by the actual level of friction but also by the other individual and environmental factors noted above. Recommendations for future studies would include a longitudinal design to better capture the temporal sequence between these variables. More field research is needed to better understand the association between workplace conditions, worker perception of slipperiness, and slipping at work.

  13. Genetic and pharmacological factors that influence reproductive aging in nematodes.

    PubMed

    Hughes, Stacie E; Evason, Kimberley; Xiong, Chengjie; Kornfeld, Kerry

    2007-02-16

    Age-related degenerative changes in the reproductive system are an important aspect of aging, because reproductive success is the major determinant of evolutionary fitness. Caenorhabditis elegans is a prominent organism for studies of somatic aging, since many factors that extend adult lifespan have been identified. However, mechanisms that control reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmental stress influence reproductive aging. Cold temperature delayed reproductive aging. The anticonvulsant medicine ethosuximide, which affects neural activity, delayed reproductive aging, indicating that neural activity can influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulate the level of early reproduction. Early progeny production neither accelerated nor delayed reproductive aging, indicating that reproductive aging is not controlled by use-dependent mechanisms. The implications of these findings for evolutionary theories of aging are discussed.

  14. Exploring the factors influencing clinical students' self-regulated learning.

    PubMed

    Berkhout, Joris J; Helmich, Esther; Teunissen, Pim W; van den Berg, Joost W; van der Vleuten, Cees P M; Jaarsma, A Debbie C

    2015-06-01

    The importance of self-regulated learning (SRL) has been broadly recognised by medical education institutions and regulatory bodies. Supporting the development of SRL skills has proven difficult because self-regulation is a complex interactive process and we know relatively little about the factors influencing this process in real practice settings. The aim of our study was therefore to identify factors that support or hamper medical students' SRL in a clinical context. We conducted a constructivist grounded theory study using semi-structured interviews with 17 medical students from two universities enrolled in clerkships. Participants were purposively sampled to ensure variety in age, gender, experience and current clerkship. The Day Reconstruction Method was used to help participants remember their activities of the previous day. The interviews were transcribed verbatim and analysed iteratively using constant comparison and open, axial and interpretive coding. Self-regulated learning by students in the clinical environment was influenced by the specific goals perceived by students, the autonomy they experienced, the learning opportunities they were given or created themselves, and the anticipated outcomes of an activity. All of these factors were affected by personal, contextual and social attributes. Self-regulated learning of medical students in the clinical environment is different for every individual. The factors influencing this process are affected by personal, social and contextual attributes. Some of these are similar to those known from previous research in classroom settings, but others are unique to the clinical environment and include the facilities available, the role of patients, and social relationships pertaining to peers and other hospital staff. To better support students' SRL, we believe it is important to increase students' metacognitive awareness and to offer students more tailored learning opportunities. © 2015 John Wiley & Sons Ltd.

  15. Abuse of Working Children and Influencing Factors, Turkey

    ERIC Educational Resources Information Center

    Oncu, Emine; Kurt, Ahmet Oner; Esenay, Figen Isik; Ozer, Fatma

    2013-01-01

    Objective: The study was planned as the research of the kind/kinds of abuse and the factors influencing the abuse that the children under 18 who are working full-time at a workplace and enrolled in a vocational training center subjected to. Method: Questionnaires were administered to 595 apprentices who were attending a vocational training center.…

  16. P14.21 Can vascular risk factors influence number of brain metastases?

    PubMed Central

    Berk, B.; Nagel, S.; Kortmann, R.; Hoffmann, K.; Gaudino, C.; Seidel, C.

    2017-01-01

    Abstract BACKGROUND: Up to 30-40% of patients with solid tumors develop cerebral metastases. Number of cerebral metastases is relevant for treatment and prognosis. However, factors that determine number of metastases are not well defined. Distribution of metastases is influenced by blood vessels and cerebral small vessel disease can reduce number of metastases. Aim of this pilot study was to analyze the influence of vascular risk factors (arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia) and of peripheral arterial occlusive disease (PAOD) on number of brain metastases. METHODS: 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Number of metastases (NoM) was compared between patients with/without vascular risk factors (vasRF). Results: Patients with PAOD had significant less brain metastases than patients without PAOD (NoM=4.43 vs. 6.02, p=0.043), no other single vasRF conferred a significant effect on NoM. NoM differed significantly between different tumor entities. CONCLUSION: Presence of PAOD showed some effect on number of brain metastases implying that tumor-independent vascular factors can influence brain metastasation.

  17. Factors Influencing Postsecondary Education Enrollment Behaviors of Urban Agricultural Education Students

    ERIC Educational Resources Information Center

    Esters, Levon T.

    2007-01-01

    The purpose of this study was to identify the factors that influenced the postsecondary education enrollment behaviors of students who graduated from an urban agricultural education program. Students indicated that parents and/or guardians had the most influence on their decisions to enroll in a postsecondary education program of agriculture.…

  18. Factors influencing avian communities in high-elevation southern Allegheny mountain forests

    Treesearch

    Harry A. Kahler; James T. Anderson

    2010-01-01

    Myriad factors may influence bird community characteristics among subalpine, central, and northern hardwood forest cover types of the southern Allegheny Mountains. Differences in forest cover types may result from natural characteristics, such as tree species composition, topography, or elevation, as well as from past influences, such as poor logging practices. Our...

  19. Metal Oxide Gas Sensors: Sensitivity and Influencing Factors

    PubMed Central

    Wang, Chengxiang; Yin, Longwei; Zhang, Luyuan; Xiang, Dong; Gao, Rui

    2010-01-01

    Conductometric semiconducting metal oxide gas sensors have been widely used and investigated in the detection of gases. Investigations have indicated that the gas sensing process is strongly related to surface reactions, so one of the important parameters of gas sensors, the sensitivity of the metal oxide based materials, will change with the factors influencing the surface reactions, such as chemical components, surface-modification and microstructures of sensing layers, temperature and humidity. In this brief review, attention will be focused on changes of sensitivity of conductometric semiconducting metal oxide gas sensors due to the five factors mentioned above. PMID:22294916

  20. Implementation of the Southwestern Oncology Group Committee on Women’s Health Research Agenda: A Special Sabbatical for the Chairperson.

    DTIC Science & Technology

    1996-07-01

    phase II study 1987-1989 Principal Investigator, Loyola/Hines pilot study of cisplatin preceded by concurrent cytarabine and oral hydroxyurea in...Investigator, Loyola/Hines pilot study of cisplatin preceded by concurrent 31 5 intravenous hydroxyurea and cytarabine . 1989-1992 Primary Study Coordinator...Conference: Modulation of cisplatin resistance by cytarabine and hydroxyurea. Illinois Cancer Council Annual Symposium: Review of Breast Cancer Growth

  1. Early Diagnosis, Treatment and Care of Cancer Patients

    DTIC Science & Technology

    2011-09-01

    parthenolide or parthenolide analogs enhance the damage caused by cytarabine . (Months 1-24) Our work on this task was described in the 2009...cisplatin, cyclophasphamide, vincristine, cytarabine , 5-fluorouracil and tamoxifen. We also have examined multiple regions of the CNS. We also...exhibit more extensive damage from cytarabine , parthenolide (or parthenolide analogs) or the combination of these agents, than those in which purified

  2. [New nurse turnover intention and influencing factors].

    PubMed

    Han, Sang Sook; Sohn, In Soon; Kim, Nam Eun

    2009-12-01

    The study was done to identify turnover intention in new nurses according to characteristics of the nurses and other factors affecting turnover and to provide data to set up a strategy to reduce the turnover. Data were collected from 1,077 new nurses who had less than 12 months employment experience and worked in one of 188 hospitals. Eight research instruments were used. Data analysis was done using SPSS WIN 15.0 program. Several factors influence new nurse turnover intention. The average score for turnover intention was 2.12. The scores for subscales were self efficacy, 3.76, nursing performance, 3.90, job satisfaction, 2.09, organization commitment, 1.28, stress, 1.32, burnout, 2.82 and nursing organizational culture, 3.29. Turnover intention was related to self efficacy, nursing performance, job satisfaction, organization commitment, stress, burnout, nursing organizational culture, duration of in-class training, duration of on the job training, number of hospital beds, length of employment and duration of employment in current workplace. The predicting factors for turnover intention were burnout, stress, duration of employment in the current workplace, self efficacy and nursing performance. Those factors explained 51.6% of turnover intention. New nurse turnover intention can be reduced by mitigating the factors affecting this intention.

  3. The Influence of Platelet-Derived Growth Factor and Fibroblast Growth Factor 2 on Oligodendrocyte Development and Remyelination

    DTIC Science & Technology

    2004-01-01

    OLIGODENDROCYTE DEVELOPMENT AND REMYELINATION 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...Z39-18 ABSTRACT Title: THE INFLUENCE OF PLATELET-DERIVED GROWTH FACTOR AND FIBROBLAST GROWTH FACTOR 2 ON OLIGODENDROCYTE DEVELOPMENT AND...GROWTH FACTOR 2 ON OLIGODENDROCYTE DEVELOPMENT AND REMYELINATION by Joshua C. Murtie Thesis/dissertation submitted to the

  4. Factors That Influence Breastfeeding Initiation Among African American Women.

    PubMed

    Hinson, Tyonne D; Skinner, Asheley Cockrell; Lich, Kristen Hassmiller; Spatz, Diane L

    2018-05-01

    To examine cultural and socioenvironmental factors that affect breastfeeding initiation among African American women. Qualitative descriptive design and conventional content analysis. A large, inner-city, primary care center affiliated with a 500-bed children's hospital within a large, Northeastern U.S. city. Participants were 34 U.S.-born African American mothers of healthy term infants 0 to 3 months of age. Six focus groups were conducted using a 16-question, scripted interview guide. A number of complex factors that influenced breastfeeding initiation included certain cultural beliefs about sexuality, the influence of family and peer networks, information sources, intentions, and a variety of other barriers and facilitators. Our findings suggest that the decision to initiate breastfeeding is not solely determined by the woman within the African American community. Because this decision is contingent on multiple factors external to the woman, it is important to recognize the role that partners, grandmothers, communities, information sources, and health care providers/organizations play in women's decisions. Implementation of multilevel strategies is critical to increase breastfeeding initiation among African American mothers. Copyright © 2018 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  5. Research on Factors Influencing Individual's Behavior of Energy Management

    NASA Astrophysics Data System (ADS)

    Fan, Yanfeng

    With the rapid rise of distributed generation, Internet of Things, and mobile Internet, both U.S. and European smart home manufacturers have developed energy management solutions for individual usage. These applications help people manage their energy consumption more efficiently. Domestic manufacturers have also launched similar products. This paper focuses on the factors influencing Energy Management Behaviour (EMB) at the individual level. By reviewing academic literature, conducting surveys in Beijing, Shanghai and Guangzhou, the author builds an integrated behavioural energy management model of the Chinese energy consumers. This paper takes the vague term of EMB and redefines it as a function of two separate behavioural concepts: Energy Management Intention (EMI), and the traditional Energy Saving Intention (ESI). Secondly, the author conducts statistical analyses on these two behavioural concepts. EMI is the main driver behind an individual's EMB. EMI is affected by Behavioural Attitudes, Subjective Norms, and Perceived Behavioural Control (PBC). Among these three key factors, PBC exerts the strongest influence. This implies that the promotion of the energy management concept is mainly driven by good application user experience (UX). The traditional ESI also demonstrates positive influence on EMB, but its impact is weaker than the impacts arising under EMI's three factors. In other words, the government and manufacturers may not be able to change an individual's energy management behaviour if they rely solely on their traditional promotion strategies. In addition, the study finds that the government may achieve better promotional results by launching subsidies to the manufacturers of these kinds of applications and smart appliances.

  6. Influencing factors of domestic waste characteristics in rural areas of developing countries.

    PubMed

    Han, Zhiyong; Liu, Yong; Zhong, Min; Shi, Guozhong; Li, Qibin; Zeng, Dan; Zhang, Yu; Fei, Yongqiang; Xie, Yanhua

    2018-02-01

    Waste management in rural areas has become a major challenge for governments of developing countries. The success of waste management decisions directly lies in the accuracy and reliability of the data on which choices are based; many factors influence these data. Here, we examined the factors influencing domestic waste in rural areas of developing countries (RADIC), using both field surveys and by reviewing previous literature. The social factors included population, education and culture. There was a positive linear relationship between waste generation amount and population size (R 2  = 0.9405). Environmental education, training and demonstration projects played a positive role in improving people's awareness of the benefits of recycling and reducing waste. Traditional and national cultures, consumption and living habits contributed to variations in the generation and composition of domestic waste. Generally, practices related to conservation of and reverence for nature and green consumption encourage people to reduce, reuse and recycle waste in their daily life. Economic factors included household income and expenditure, energy and fuel structure, and types of industry that occurred in villages. A Kuznets inverted "U" curve relationship existed between domestic waste generation and people's income in rural areas of China. However, the waste generation rate had a linear relationship with the gross national income per capita in RADIC. The composition, bulk density and calorific value of domestic waste were variously affected by the energy and fuel structure and the types of industry that occurred. The natural factors included geography and climate (including rainfall, humidity, temperature and harvest seasons). The moisture content of waste was directly influenced by rainfall and humidity. Temperature affected waste characteristics by influencing residential heating modes. The waste characteristics were also influenced by the mixing of agricultural and

  7. Factors that influence engagement in collaborative practice

    PubMed Central

    Herbert, Carol P.; Bainbridge, Lesley; Bickford, Julia; Baptiste, Susan; Brajtman, Susan; Dryden, Trish; Hall, Pippa; Risdon, Cathy; Solomon, Patricia

    2007-01-01

    OBJECTIVE To generate hypotheses regarding factors that might influence engagement in collaborative practice. DESIGN Qualitative study using in-depth interviews. SETTING Participants interviewed each other in dyads. The pairing was based upon geographical location and proximity to each other. PARTICIPANTS Eight professionals from the disciplines of medicine, nursing, occupational therapy, physical therapy, and massage therapy. METHOD Semistructured interviews, lasting 30 to 45 minutes each, were recorded and transcribed verbatim. The transcripts were read by all research team members using independent content analysis for common words, phrases, statements, or units of text for key themes. At a subsequent face-to-face meeting, the team used an iterative process of comparing and contrasting key themes until consensus was reached. The transcripts were then analyzed further for subthemes using NVivo software. MAIN FINDINGS Initial findings suggest that some common characteristics grounded in family history, school experiences, social interactions, and professional training might influence collaborative practice choices. The narrative form of the interview broke down interpersonal and interprofessional barriers, creating a new level of trust and respect that could improve professional collaboration. CONCLUSION This study suggests that life experiences from childhood into later adulthood can and do influence professional choices. PMID:17872847

  8. A review of major factors influencing plant responses to recreation impacts

    NASA Astrophysics Data System (ADS)

    Kuss, Fred R.

    1986-09-01

    This article reviews some of the more important factors found to influence the susceptibility of plants to trampling impacts associated with recreational use of natural areas. A three-way interaction mediates plant responses to impacts: plant x environment x stress level(s). Plant responses vary in part according to the genetic constitution of the plant, life and growth form, the adaptive flexibility of the plant, and anatomical differences inherent to growth habit and morphology. Other factors that influence plant sensitivities to impacts are the habitat environments in which plants grow, since a number of conditions such as moisture excesses or deficiencies, nitrogen or oxygen starvation, late frosts, etc., cause physiological injury and may increase plant sensitivity to impacts. Among the environmental factors that may increase or lessen plant sensitivities to impacts are soil moisture levels, canopy density, elevation, aspect, microclimate, soil drainage, texture, fertility and productivity. Seasonal influences also bear consideration since environmental changes and phonological and physiological events are mediated by time of year. Stresses are caused by both direct and indirect forms of impact and vary according to season of use, frequency and amount of use, and the type of activity. These interactions are further complicated by evidence that inter- and intraspecific competition, antagonism, and commensalism may influence differences in the sensitivity of plant communities to impacts.

  9. Factors influencing seasonal influenza vaccination behaviour among elderly people: a systematic review.

    PubMed

    Kan, T; Zhang, J

    2018-03-01

    To explore the behaviour-related factors influencing influenza vaccination among elderly people using a framework derived from the Health Belief Model (HBM) and the Theory of Reasoned Action (TRA). Systematic review. Five databases were searched using predetermined strategies in March 2016, and 1927 citations were identified. Articles were selected according to inclusion and exclusion criteria. Key information was extracted from selected studies using a predesigned sheet. Both authors assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) or Critical Appraisal Skills Programme (CASP) checklist. Thirty-six articles were selected. A new framework was proposed that contributes to shared understanding of factors influencing health behaviour. Possible determinants of influenza vaccination among elderly people were knowledge, health promotion factors, all constructs of the HBM, and some concepts of the TRA. Key factors were threat perception, behavioural beliefs, subjective norms, recommendations, past behaviour and perceived barriers. This is the first systematic review to analyse the factors influencing influenza vaccination behaviour of elderly people using a framework integrating the HBM and the TRA. The framework identified key factors of influenza vaccination and presented the inter-relation of behaviour-related variables. However, further well-designed studies are required to explore the inter-relationships accurately and comprehensively. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  10. Social Factors Influencing Participation in Sport for the Deaf.

    ERIC Educational Resources Information Center

    Stewart, David A.

    1987-01-01

    The article looks at social factors influencing participation in sport by the deaf including communication mode and value orientations of community, family, school, and peers of both the hearing and deaf world. A model for integration of the deaf into sports is offered. (DB)

  11. Factors Influencing Role Behaviors by Professional Exemplars in Hospitals

    ERIC Educational Resources Information Center

    Bolding, Deborah J.

    2013-01-01

    This basic qualitative study explored factors that influenced the development of professional role behaviors of nurses, occupational and physical therapists who were characterized as exemplars in the acute hospital setting. The participants, four occupational therapists, four nurses, and four physical therapists were interviewed using a…

  12. Factors That Influence the Receipt of Eye Care

    PubMed Central

    Alexander, Robert L.; Miller, Nancy A.; Cotch, Mary Frances; Janiszewski, Rosemary

    2010-01-01

    Objectives To better understand what factors influence the receipt of eye care so that screening and education programs can be designed to promote early detection and treatment. Methods Twenty focus groups were conducted. Analyses entailed debriefing sessions, coding, and interpreting transcribed data. Results Attitudes about eyesight and eye exams influence the receipt of preventive eye care. Limited knowledge about certain eye diseases and conditions was reported. Participants stated that their primary care providers did not communicate information with them about eyesight nor did they conduct basic eye screenings. Conclusions Improving provider-patient interactions and developing public health messages about eye diseases and preventive eye care can facilitate increased use of appropriate eye care services. PMID:18241139

  13. Factors Influencing Belize District Primary School Teachers' Attitudes toward Inclusive Education

    ERIC Educational Resources Information Center

    McKay, Maxine

    2012-01-01

    Inclusive education continues to be a reoccurring challenge as various factors affect to what extent teachers or educators are willing to educate children with disabilities in the regular education setting alongside their non-disabled peers. This quantitative study examined factors influencing Belize District Primary School teachers' attitudes…

  14. Factors Influencing Cecal Intubation Time during Retrograde Approach Single-Balloon Enteroscopy

    PubMed Central

    Chen, Peng-Jen; Shih, Yu-Lueng; Huang, Hsin-Hung; Hsieh, Tsai-Yuan

    2014-01-01

    Background and Aim. The predisposing factors for prolonged cecal intubation time (CIT) during colonoscopy have been well identified. However, the factors influencing CIT during retrograde SBE have not been addressed. The aim of this study was to determine the factors influencing CIT during retrograde SBE. Methods. We investigated patients who underwent retrograde SBE at a medical center from January 2011 to March 2014. The medical charts and SBE reports were reviewed. The patients' characteristics and procedure-associated data were recorded. These data were analyzed with univariate analysis as well as multivariate logistic regression analysis to identify the possible predisposing factors. Results. We enrolled 66 patients into this study. The median CIT was 17.4 minutes. With univariate analysis, there was no statistical difference in age, sex, BMI, or history of abdominal surgery, except for bowel preparation (P = 0.021). Multivariate logistic regression analysis showed that inadequate bowel preparation (odds ratio 30.2, 95% confidence interval 4.63–196.54; P < 0.001) was the independent predisposing factors for prolonged CIT during retrograde SBE. Conclusions. For experienced endoscopist, inadequate bowel preparation was the independent predisposing factor for prolonged CIT during retrograde SBE. PMID:25505904

  15. Factors influencing European GPs' engagement in smoking cessation: a multi-country literature review.

    PubMed

    Stead, Martine; Angus, Kathryn; Holme, Ingrid; Cohen, David; Tait, Gayle

    2009-09-01

    Smoking cessation advice by GPs is an effective and cost-effective intervention, but is not implemented as widely as it could be. This wide-ranging Europe-wide literature review, part of the European Union (EU) PESCE (General Practitioners and the Economics of Smoking Cessation in Europe) project, explored the extent of GPs' engagement in smoking cessation and the factors that influence their engagement. Two searches were conducted, one for grey literature, across all European countries, and one for academic studies. Data from eligible studies published from 1990 onwards were synthesised and reported under four categories of influencing factors: GP characteristics, patient characteristics, structural factors, and cessation-specific knowledge and skills. The literature showed that most GPs in Europe question the smoking status of all new patients but fewer routinely ask this of regular patients, or advise smokers to quit. The proportion offering intensive interventions or prescribing treatments is lower still. Factors influencing GPs' engagement in smoking cessation include GPs' own smoking status and their attitudes towards giving smoking cessation advice; whether patients present with smoking-related symptoms, are pregnant, or heavy smokers; time, training, and reimbursement are important structural factors; and some GPs lack knowledge and skills regarding the use of specific cessation methods and treatments, or have limited awareness of specialist cessation services. No single factor or category of factors explains the variations in GPs' engagement in smoking cessation. Strategies to improve the frequency and quality of GPs' engagement in smoking cessation need to address the multifaceted influences on GPs' practice and to reflect the widely differing contexts across Europe.

  16. Factors influencing intentions to use social recommender systems: a social exchange perspective.

    PubMed

    Chang, Tsung-Sheng; Hsiao, Wei-Hung

    2013-05-01

    This study employs the perspective of social exchange theory and seeks to understand users' intentions to use social recommender systems (SRS) through three psychological factors: trust, shared values, and reputation. We use structural equation modeling to analyze 221 valid questionnaires. The results show that trust has a direct positive influence on the intention to use SRS, followed by shared values, whereas reputation has an indirect influence on SRS use. We further discuss specific recommendations concerning these factors for developing SRS.

  17. Environmental and genetic factors influence the vitamin D content of cows' milk.

    PubMed

    Weir, R R; Strain, J J; Johnston, M; Lowis, C; Fearon, A M; Stewart, S; Pourshahidi, L K

    2017-02-01

    Vitamin D is obtained by cattle from the diet and from skin production via UVB exposure from sunlight. The vitamin D status of the cow impacts the vitamin D content of the milk produced, much like human breast milk, with seasonal variation in the vitamin D content of milk well documented. Factors such as changes in husbandry practices therefore have the potential to impact the vitamin D content of milk. For example, a shift to year-round housing from traditional practices of cattle being out to graze during the summer months and housed during the winter only, minimises exposure to the sun and has been shown to negatively influence the vitamin D content of the milk produced. Other practices such as changing dietary sources of vitamin D may also influence the vitamin D content of milk, and evidence exists to suggest genetic factors such as breed can cause variation in the concentrations of vitamin D in the milk produced. The present review aims to provide an overview of the current understanding of how genetic and environmental factors influence the vitamin D content of the milk produced by dairy cattle. A number of environmental and genetic factors have previously been identified as having influence on the nutritional content of the milk produced. The present review highlights a need for further research to fully elucidate how farmers could manipulate the factors identified to their advantage with respect to increasing the vitamin D content of milk and standardising it across the year.

  18. 41 CFR 105-68.880 - What factors may influence the debarring official during reconsideration?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What factors may influence the debarring official during reconsideration? 105-68.880 Section 105-68.880 Public Contracts and... (NONPROCUREMENT) Debarment § 105-68.880 What factors may influence the debarring official during reconsideration...

  19. Factors influencing parental decision making about stimulant treatment for attention-deficit/hyperactivity disorder.

    PubMed

    Ahmed, Rana; McCaffery, Kirsten J; Aslani, Parisa

    2013-04-01

    Attention-deficit/hyperactivity disorder (ADHD) is a pediatric psychological condition commonly treated with stimulant medications. Negative media reports and stigmatizing societal attitudes surrounding the use of these medications make it difficult for parents of affected children to accept stimulant treatment, despite it being first line therapy. The purpose of this study was to identify factors that influence parental decision making regarding stimulant treatment for ADHD. A systematic review of the literature was conducted to identify studies: 1) that employed qualitative methodology, 2) that highlighted treatment decision(s) about stimulant medication, 3) in which the decision(s) were made by the parent of a child with an official ADHD diagnosis, and 4) that examined the factors affecting the decision(s) made. Individual factors influencing parental treatment decision making, and the major themes encompassing these factors, were identified and followed by a thematic analysis. Eleven studies reporting on the experiences of 335 parents of children with ADHD were included. Four major themes encompassing influences on parents' decisions were derived from the thematic analysis performed: confronting the diagnosis, external influences, apprehension regarding therapy, and experience with the healthcare system. The findings of this systematic review reveal that there are multiple factors that influence parents' decisions about stimulant therapy. This information can assist clinicians in enhancing information delivery to parents of children with ADHD, and help reduce parental ambivalence surrounding stimulant medication use. Future work needs to address parental concerns about stimulants, and increase their involvement in shared decision making with clinicians to empower them to make the most appropriate treatment decision for their child.

  20. Practice location factors influencing South Dakota School of Medicine graduates (1977-85).

    PubMed

    Jarratt, L G; Leonardson, G R; Nord, W J

    1989-12-01

    Physician numbers and placement continue to be major health delivery concerns in the rural state of South Dakota. This study of four-year graduates (1977-1985) of the South Dakota School of Medicine looks at current factors affecting physician placement and compares placement and location selection factors to a previous study of graduates of the medical school when it was a two-year program (1969-1973). Factors influencing physicians locating in South Dakota were: closeness to their home town and or spouses' home town, residency training in small towns, payment of educational loans, medical school clerkships, time of decision, etc. Factors influencing physicians locating in rural communities (less than 5,000) were: growing up in small communities, residency training in small communities, early location decisions, payment of loans, and high medical need.

  1. Factors influencing patient compliance with therapeutic regimens in chronic heart failure: A critical incident technique analysis.

    PubMed

    Strömberg, A; Broström, A; Dahlström, U; Fridlund, B

    1999-01-01

    The aim of this study was to identify factors influencing compliance with prescribed treatment in patients with chronic heart failure. A qualitative design with a critical incident technique was used. Incidents were collected through interviews with 25 patients with heart failure strategically selected from a primary health care clinic, a medical ward, and a specialist clinic. Two hundred sixty critical incidents were identified in the interviews and 2 main areas emerged in the analysis: inward factors and outward factors. The inward factors described how compliance was influenced by the personality of the patient, the disease, and the treatment. The outward factors described how compliance was influenced by social activities, social relationships, and health care professionals. By identifying the inward and outward factors influencing patients with chronic heart failure, health care professionals can assess whether intervention is needed to increase compliance.

  2. Factor Influencing Creative Industries Development in Kenjeran Surabaya

    NASA Astrophysics Data System (ADS)

    Siswanto, V. K.; Santoso, E. B.

    2017-07-01

    Indonesia needs to improve the competitiveness of local products to optimize its contribution to the ASEAN Economic Community (AEC) for the welfare of the population. This can be done by improving the development of creative industries. Kenjeran Sub District is one of the coastal villages in the city of Surabaya, which has a large number of poor people. The potential of the creative industries is still not visible in efforts to increase public welfare. Therefore, it is necessary to investigate the factors that influence the development of creative industries in Kenjeran. This study using in-depth interview were analysed using content analysis and Cartesian diagram to determine the important factors that affect the development of creative industries in Sub district of Kenjeran. By using five respondents from the government shows that the factors that have a high level of importance and advantages are low among other regulatory factors of raw materials, import and export, extortion, and administrative procedures.

  3. Factors Influencing Stress, Burnout, and Retention of Secondary Teachers

    ERIC Educational Resources Information Center

    Fisher, Molly H.

    2011-01-01

    This study examines the stress, burnout, satisfaction, and preventive coping skills of nearly 400 secondary teachers to determine variables contributing to these major factors influencing teachers. Analysis of Variance (ANOVA) statistics were conducted that found the burnout levels between new and experienced teachers are significantly different,…

  4. Factors Influencing the College Choice Decisions of Graduate Students.

    ERIC Educational Resources Information Center

    Kallio, Ruth E.

    1995-01-01

    A study investigated the relative importance of 31 institutional characteristics in 1,068 graduate students' decisions to enroll or not enroll in the institution. Factors having the greatest influence included residency status, quality and other academic environment characteristics, work-related concerns, spouse considerations, financial aid, and…

  5. Factors Influencing Student Participation in College Study Abroad Programs

    ERIC Educational Resources Information Center

    Bandyopadhyay, Soumava; Bandyopadhyay, Kakoli

    2015-01-01

    This paper proposes a theoretical framework to investigate the factors that influence student participation in college study abroad programs. The authors posit that students' general perceptions regarding the study abroad experience and their expectations of intercultural awareness from study abroad programs will impact their perceptions of…

  6. Against Conventional Wisdom: Factors Influencing Hispanic Students' Reading Achievement

    ERIC Educational Resources Information Center

    Percell, Jay C.; Kaufman, Kristina

    2013-01-01

    The researchers performed a variable analysis of the 2002 Educational Longitudinal Study data investigating factors that influence students' reading scores on standardized tests. Hispanic and non-Hispanic Scores were analyzed and controlling variables were compared to determine the effect of each on both populations. Certain variables commonly…

  7. Factors Influencing Radiology Residents' Fellowship Training and Practice Preferences in Canada.

    PubMed

    Mok, Philip S; Probyn, Linda; Finlay, Karen

    2016-05-01

    The study aimed to examine the postresidency plans of Canadian radiology residents and factors influencing their fellowship choices and practice preferences, including interest in teaching and research. Institutional ethics approval was obtained at McMaster University. Electronic surveys were sent to second to fifth-year residents at all 16 radiology residency programs across Canada. Each survey assessed factors influencing fellowship choices and practice preferences. A total of 103 (31%) Canadian radiology residents responded to the online survey. Over 89% from English-speaking programs intended to pursue fellowship training compared to 55% of residents from French-speaking programs. The most important factors influencing residents' decision to pursue fellowship training were enhanced employability (46%) and personal interest (47%). Top fellowship choices were musculoskeletal imaging (19%), body imaging (17%), vascular or interventional (14%), neuroradiology (8%), and women's imaging (7%). Respondents received the majority of their fellowship information from peers (68%), staff radiologists (61%), and university websites (58%). Approximately 59% planned on practicing at academic institutions and stated that lifestyle (43%), job prospects (29%), and teaching opportunities (27%) were the most important factors influencing their decisions. A total of 89% were interested in teaching but only 46% were interested in incorporating research into their future practice. The majority of radiology residents plan on pursuing fellowship training and often receive their fellowship information from informal sources such as peers and staff radiologists. Fellowship directors can incorporate recruitment strategies such as mentorship programs and improving program websites. There is a need to increase resident participation in research to advance the future of radiology. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  8. Factors Influencing E-Portfolio Use and Students' Approaches to Learning in Higher Education

    ERIC Educational Resources Information Center

    Sánchez, Andrea Ximena Castaño; Soto, Ángel Pío González; González, José Miguel Jiménez

    2015-01-01

    The aim of this study is to analyze the factors influencing eportfolio use in higher education and its implication on students' learning. These relationships are investigated under different stimulated conditions that have offered the potential for more understanding of the influencing factors in the investigated context. University students (N =…

  9. Gender differences in how retirees perceive factors influencing unretirement.

    PubMed

    Armstrong-Stassen, Marjorie; Staats, Sara

    2012-01-01

    Returning to paid employment after retirement is occurring in many developed countries and can be expected to increase in the future. This study compared how women (n = 202) and men (n = 347) who had retired from a managerial or professional career occupation perceived factors associated with unretirement. Retired professional women perceived reasons to unretire, age-friendly human resource practices, and re-entry barriers to have greater influence on retirees' decision to unretire than retired managerial women and retired men. Both groups of retired women perceived training and development opportunities to have more influence than retired men. A major contribution of this study is the identification of pre-retirement career occupation as having an important effect on how female, but not male, retirees perceived the various factors. The findings suggest that researchers and employers need to consider the diversity that exists among retirees, not only gender differences but also differences among retired career women.

  10. Factors influencing health-related quality of life among Korean cancer survivors.

    PubMed

    Kim, KiSook; Kim, Ji-Su

    2017-01-01

    Early cancer detection and remarkable improvements in cancer treatment have seen the cancer survival rate grow steadily for the past 40 years. Despite expectations regarding treatment effectiveness, acceptable quality of life, and a comfortable death, patients with cancer generally have a decreased quality of life. The study aim was to examine the factors influencing health-related quality of life among South Korean cancer survivors for future development of an intervention to enhance their survivorship. Korea National Health and Nutrition Examination Survey 2008-2012 data regarding 1020 cancer survivors were used for analysis. Health-related quality of life was measured using the EuroQol 5-Dimension. The factors influencing health-related quality of life were age, educational status, employment status, income, smoking, time since diagnosis, subjective health status, stress, depression, and suicidal ideation. Individual-centered clinical interventions that consider dimensional-influencing factors, including subjective health status, are needed to improve cancer survivors' health-related quality of life. Subsequent systematic studies are needed regarding dimension-specific differences according to cancer types and time since diagnosis. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Multiple Factors Influence Glomerular Albumin Permeability in Rats

    PubMed Central

    Sandoval, Ruben M.; Wagner, Mark C.; Patel, Monica; Campos-Bilderback, Silvia B.; Rhodes, George J.; Wang, Exing; Wean, Sarah E.; Clendenon, Sherry S.

    2012-01-01

    Different laboratories recently reported incongruous results describing the quantification of albumin filtration using two-photon microscopy. We investigated the factors that influence the glomerular sieving coefficient for albumin (GSCA) in an effort to explain these discordant reports and to develop standard operating procedures for determining GSCA. Multiple factors influenced GSCA, including the kidney depth of image acquisition (10–20 μm was appropriate), the selection of fluorophore (probes emitting longer wavelengths were superior), the selection of plasma regions for fluorescence measurements, the size and molecular dispersion characteristics of dextran polymers if used, dietary status, and the genetic strain of rat. Fasting reduced the GSCA in Simonsen Munich Wistar rats from 0.035±0.005 to 0.016±0.004 (P<0.01). Frömter Munich Wistar rats had a much lower GSCA in both the fed and the fasted states. Finally, we documented extensive albumin transcytosis with vesicular and tubular delivery to and fusion with the basolateral membrane in S1 proximal tubule cells. In summary, these results help explain the previously conflicting microscopy and micropuncture data describing albumin filtration and highlight the dynamic nature of glomerular albumin permeability. PMID:22223875

  12. Factors Influencing the Appearance of Oxaliplatin-Induced Allergy.

    PubMed

    Nishihara, Masayuki; Nishikura, Kyoko; Morikawa, Norimichi; Yokoyama, Shota

    2017-01-01

    Several studies reported that the administration of oxaliplatin often induced allergy, but few studies have analyzed the pathogenesis. In this study, we examined the relationship between the incidence of allergy and status of oxaliplatin administration, patient background, laboratory data, or combined drugs. The subjects were 144 patients with colorectal or gastric cancer in whom oxaliplatin administration was started and completed between 2010 and 2016. They were divided into 2 groups: allergy and non-allergy groups. We extracted important factors influencing its appearance using multivariate analysis, and analyzed items of which the influence was suggested, using receiver operating characteristic (ROC) analysis. In 11 patients (7.6%), allergy appeared. The median frequency of appearance was 9 times (range: 5-13), being similar to that previously reported. On multivariate analysis, albumin (Alb) was extracted as an important factor. The cut-off value of Alb for the risk of allergy was 4.1 g/dL. An increase in the number of protein conjugates may have increased the risk of functioning as a hapten. Furthermore, the results suggested that the more frequency of oxaliplatin administration might increase the incidence of allergy, although it was not extracted as an important factor. In addition to young and female patients, as previously indicated, careful follow-up may be necessary for those with an Alb level of ≥4.1 g/dL especially after the 6th course.

  13. Psychosocial Aspects of Bruxism: The Most Paramount Factor Influencing Teeth Grinding

    PubMed Central

    Wieckiewicz, Mieszko; Paradowska-Stolarz, Anna; Wieckiewicz, Wlodzimierz

    2014-01-01

    In clinical practice, patients suffering from an occlusal parafunctional activity have increased. It can be observed that a negative influence of environment aggravates patient's health. The aim of this paper is to present the impact of environment and development of human civilization on the prevalence of bruxism and the correlation between them. The authors grasp the most relevant aspects of psychological and anthropological factors changing over time as well as their interactions and describe a relationship between chronic stress and bruxism. Current literature shows how contemporary lifestyle, working environment, diet, and habits influence the patient's psychoemotional situation and the way these factors affect the occluso-muscle condition. PMID:25101282

  14. [Factors that influence treatment adherence in chronic disease patients undergoing hemodialysis].

    PubMed

    Maldaner, Cláudia Regina; Beuter, Margrid; Brondani, Cecília Maria; Budó, Maria de Lourdes Denardin; Pauletto, Macilene Regina

    2008-12-01

    The following bibliographical research wanted to identify the main factors that influence adherence to treatment in chronic disease. The study focused on patients undergoing hemodialysis, as well as on the support nurses require for the promotion of health education among individuals with low treatment adherence. The identification of bibliographical sources was conducted at Health Virtual Library and Scientific Electronic Library Online (SciELO) data bases. Some printed magazines were also used. The results indicated nine factors influencing treatment adherence or non-adherence: team trust, support nets, educational level; accepting disease, treatment side effects, lack of access to medicines, long-term treatment, complex therapeutic approach, and lack of symptoms. It is advisable that nurses take into account these factors when dealing with chronic-disease patients that present low treatment adherence, getting family and multidisciplinary team support seeking treatment adherence.

  15. Factors Influencing the ABT Phenomenon among Graduate Students in a Master Program in Mexico

    ERIC Educational Resources Information Center

    Gonzalez-Castillo, Vicente; Cisneros-Cohernour, Edith J.

    2007-01-01

    This paper presents the findings of a study examining the factors that influence the ABT phenomenon (all but thesis) among graduate students of a Master in Education program in the Southeast of Mexico. Findings of the study identified individual and organizational factors influencing ABT. The study allowed for a better understanding about how…

  16. Factors That Influence Faculty Adoption of Learning-Centered Approaches

    ERIC Educational Resources Information Center

    Blumberg, Phyllis

    2016-01-01

    This article proposes a recommended course of action for faculty development based upon Rogers' theory of Diffusion of Innovations and data collected in a study looking at the prevalence of use of learning-centered teaching practices. Specific faculty development strategies are aligned with Rogers' factors influencing decisions to adopt…

  17. Factors Influencing Latino Participation in Community-Based Diabetes Education

    ERIC Educational Resources Information Center

    Francis, Sarah L.; Noterman, Amber; Litchfield, Ruth

    2014-01-01

    An Extension diabetes program (DP) was revised for Latinos; however, participation was limited. Factors influencing low participation rates were examined. Five Latinos interested in the DP participated in a focus group discussion. Transcripts were analyzed for themes. Preferred education programs were multi-session, local, group classes led by an…

  18. Factors Influencing Trainee Participation in Computer Software Applications Training.

    ERIC Educational Resources Information Center

    Alexander, Melody Webler

    1993-01-01

    Participants (n=130) who had completed training in WordPerfect, Lotus 1-2-3, and dBase III+ completed a questionnaire related to demographic characteristics and factors that influence training participation. Trainees are participating in computer training for personal reasons, seeking convenient time, location, and length. Child care or…

  19. Factors Influencing Exemplary Science Teachers' Levels of Computer Use

    ERIC Educational Resources Information Center

    Hakverdi, Meral; Dana, Thomas M.; Swain, Colleen

    2011-01-01

    The purpose of this study was to examine exemplary science teachers' use of technology in science instruction, factors influencing their level of computer use, their level of knowledge/skills in using specific computer applications for science instruction, their use of computer-related applications/tools during their instruction, and their…

  20. Factors That Influence the Understanding of Good Mathematics Teaching

    ERIC Educational Resources Information Center

    Leong, Kwan Eu

    2013-01-01

    This study explored the factors that influenced the understanding of good mathematics teaching. A mixed methodology was used investigate the beliefs of beginning secondary teachers on good mathematics teaching. The two research instruments used in this study were the survey questionnaire and an interview. Beginning teachers selected Immediate…

  1. Factors Influencing Mini-CEX Rater Judgments and Their Practical Implications: A Systematic Literature Review.

    PubMed

    Lee, Victor; Brain, Keira; Martin, Jenepher

    2017-06-01

    At present, little is known about how mini-clinical evaluation exercise (mini-CEX) raters translate their observations into judgments and ratings. The authors of this systematic literature review aim both to identify the factors influencing mini-CEX rater judgments in the medical education setting and to translate these findings into practical implications for clinician assessors. The authors searched for internal and external factors influencing mini-CEX rater judgments in the medical education setting from 1980 to 2015 using the Ovid MEDLINE, PsycINFO, ERIC, PubMed, and Scopus databases. They extracted the following information from each study: country of origin, educational level, study design and setting, type of observation, occurrence of rater training, provision of feedback to the trainee, research question, and identified factors influencing rater judgments. The authors also conducted a quality assessment for each study. Seventeen articles met the inclusion criteria. The authors identified both internal and external factors that influence mini-CEX rater judgments. They subcategorized the internal factors into intrinsic rater factors, judgment-making factors (conceptualization, interpretation, attention, and impressions), and scoring factors (scoring integration and domain differentiation). The current theories of rater-based judgment have not helped clinicians resolve the issues of rater idiosyncrasy, bias, gestalt, and conflicting contextual factors; therefore, the authors believe the most important solution is to increase the justification of rater judgments through the use of specific narrative and contextual comments, which are more informative for trainees. Finally, more real-world research is required to bridge the gap between the theory and practice of rater cognition.

  2. Factors influencing pre-service physics teachers' skills of writing teaching materials

    NASA Astrophysics Data System (ADS)

    Sinaga, Parlindungan

    2016-02-01

    Writing teaching materials is one of the generic pedagogical skills. Teachers and pre-service teachers should be trained to have the skills of writing teaching materials. This study examines the factors that influence the skills of writing in the disciplines among pre-service physics teachers. This study in particular aims to contribute to the development of science writing in the disciplines and to the organization of workshops on writing teaching materials for pre-service teachers. The problems of this research are formulated in the question of what are the factors that influence the skills of pre-service physics teachers in writing teaching materials. The research adopted mixed methods with embedded experimental design. The research subjects were 18 students enrolled in the school physics course. The instruments used consisted of conceptual understanding tests, learning strategy questionnaire, tests of the multiple representation skills, and one-on-one semi- structured interview. Results of data analysis show that the ability and skills of writing physics teaching materials of the pre- service physics teachers are determined by the factors of conceptual understanding of the subject matter with a contribution of 20%, the skills of making multiple representations of concepts with a contribution of 9.8% and students' self-regulation and learning strategy with a contribution of 33.5%. There are other factors that have not been investigated in this study; therefore, it is recommended that future research conduct further investigation on other factors that influence pre-service teachers' skills in writing physics teaching materials.

  3. What factors influence physiotherapy service provision in rural communities? A pilot study.

    PubMed

    Adams, Robyn; Sheppard, Lorraine; Jones, Anne; Lefmann, Sophie

    2014-06-01

    To obtain stakeholder perspectives on factors influencing rural physiotherapy service provision and insights into decision making about service provision. Purposive sampling, open-ended survey questions and semi-structured interviews were used in this exploratory, qualitative study. A rural centre and its regional referral centre formed the pilot sites. Nine participant perspectives were obtained on rural physiotherapy services. Stakeholder perspectives on factors influencing rural physiotherapy service provision and service level decision making. Workforce capacity and capability, decision maker's knowledge of the role and scope of physiotherapy, consideration of physiotherapy within resource allocation decisions and proof of practice emerged as key issues. The latter three were particularly reflected in public sector participant comments. Business models and market size were identified factors in influencing private practice. Influencing factors described by participants both align and extend our understanding of issues described in the rural physiotherapy literature. Participant insights add depth and meaning to quantitative data by revealing impacts on local service provision. Available funding and facility priorities were key determinants of public sector physiotherapy service provision, with market size and business model appearing more influential in private practice. The level of self direction or choice about which services to provide, emerged as a point of difference between public and private providers. Decisions by public sector physiotherapists about service provision appear constrained by existing capacity and workload. Further research into service level decision making might provide valuable insights into rural health service delivery. © 2014 National Rural Health Alliance Inc.

  4. Factors influencing European GPs' engagement in smoking cessation: a multi-country literature review

    PubMed Central

    Stead, Martine; Angus, Kathryn; Holme, Ingrid; Cohen, David; Tait, Gayle

    2009-01-01

    Background Smoking cessation advice by GPs is an effective and cost-effective intervention, but is not implemented as widely as it could be. Aim This wide-ranging Europe-wide literature review, part of the European Union (EU) PESCE (General Practitioners and the Economics of Smoking Cessation in Europe) project, explored the extent of GPs' engagement in smoking cessation and the factors that influence their engagement. Method Two searches were conducted, one for grey literature, across all European countries, and one for academic studies. Data from eligible studies published from 1990 onwards were synthesised and reported under four categories of influencing factors: GP characteristics, patient characteristics, structural factors, and cessation-specific knowledge and skills. Results The literature showed that most GPs in Europe question the smoking status of all new patients but fewer routinely ask this of regular patients, or advise smokers to quit. The proportion offering intensive interventions or prescribing treatments is lower still. Factors influencing GPs' engagement in smoking cessation include GPs' own smoking status and their attitudes towards giving smoking cessation advice; whether patients present with smoking-related symptoms, are pregnant, or heavy smokers; time, training, and reimbursement are important structural factors; and some GPs lack knowledge and skills regarding the use of specific cessation methods and treatments, or have limited awareness of specialist cessation services. No single factor or category of factors explains the variations in GPs' engagement in smoking cessation. Conclusion Strategies to improve the frequency and quality of GPs' engagement in smoking cessation need to address the multifaceted influences on GPs' practice and to reflect the widely differing contexts across Europe. PMID:19674514

  5. Evaluation of the factors influencing brain language laterality in presurgical planning.

    PubMed

    Batouli, Seyed Amir Hossein; Hasani, Nafiseh; Gheisari, Sara; Behzad, Ebrahim; Oghabian, Mohammad Ali

    2016-10-01

    Brain lesions cause functional deficits, and one treatment for this condition is lesion resection. In most cases, presurgical planning (PSP) and the information from laterality indices are necessary for maximum preservation of the critical functions after surgery. Language laterality index (LI) is reliably estimated using functional magnetic resonance imaging (fMRI); however, this measure is under the influence of some external factors. In this study, we investigated the influence of a number of factors on language LI, using data from 120 patients (mean age=35.65 (±13.4) years) who underwent fMRI for PSP. Using two proposed language tasks from our previous works, brain left hemisphere was showed to be dominant for the language function, although a higher LI was obtained using the "Word Generation" task, compared to the "Reverse Word Reading". In addition, decline of LIs with age, and lower LI when the lesion invaded brain language area were observed. Meanwhile, gender, lesion side (affected hemisphere), LI calculation strategy, and fMRI analysis Z-values did not statistically show any influences on the LIs. Although fMRI is widely used to estimate language LI, it is shown here that in order to present a reliable language LI and to correctly select the dominant hemisphere of the brain, the influence of external factors should be carefully considered. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  6. Early Diagnosis, Treatment and Care of Cancer Patients

    DTIC Science & Technology

    2008-09-01

    these substances, and to determine whether parthenolide or parthenolide analogs enhance the damage caused by cytarabine . (Months 1-24) Progress...barrier. SOW task #2: Demonstrate that mice in which purified cells are more oxidized in vitro will exhibit more extensive damage from cytarabine ...risk for adverse side effects of therapy with W81XWH-07-1-0601 6 cytarabine , parthenolide (or parthenolide analogs) or the combination of these

  7. Stimulation of Breast Tumor Cell Proliferative Recovery by the Peptide Hormone Erythropoietin

    DTIC Science & Technology

    2006-08-01

    against apoptosis induced by chemotherapy, F-MEL leukemic cells treated with or without EPO were exposed to either cytarabine (Ara-C) or daunorubicin...F-MEL erythroleukemia cells is suppressed by treatment with cytarabine ( Ara C) or daunorubicin. Cells were incubated in the absence or presence...antiproliferative and/or cytotoxic effects of Adriamycin,Taxol, and tamoxifen in breast tumor cells (or of cytarabine and daunorubicin in F-MEL cells). EPO failed to

  8. Early Diagnosis, Treatment, and Care of Cancer Patients

    DTIC Science & Technology

    2009-09-01

    damage caused by cytarabine . (Months 1-24) The toxicity for CNS progenitor cells in vitro revealed in our first year’s work on parthenolide...and the toxicity seen for cytarabine , indicated that it was necessary to examine other relevant chemotherapeutic agents to try and identify a...task #2: Demonstrate that mice in which purified cells are more oxidized in vitro will exhibit more extensive damage from cytarabine , parthenolide (or

  9. Assessing the Mechanisms of MDS and its Transformation to Leukemia in a Novel Humanized Mouse

    DTIC Science & Technology

    2014-09-01

    mice is suboptimal (bottom). Stephanie Halene, M.D., Ph.D. 6 agents in MISTRG mice. MISTRG mice tolerated cytarabine (50mg/kg vs 100mg/kg...Chemotherapy treatment in MISTRG mice. Non-engrafted MISTRG mice were treated with vehicle, Doxorubicin, Cytarabine , or a combination of Doxorubicin and... Cytarabine . Approximately 50% of mice survive chemotherapy treatment (A) due to significant cytopenias (B, white blood cell count (top), hemoglobin (middle

  10. Off-Label Drugs. Initial Results of a National Survey

    DTIC Science & Technology

    1991-02-01

    Cisplatin. PlafinoI 4 813391 Aminoglutethimide, Cyradren 4 0 0 Cyclophosphamide. Cyroxan, Neosar M3 3061234 Chlorotrianisene, TACE 1 0 0 Cytarabine ...0 3 61 Amiinoglutethinmide, Cytadren 0 0 0 Cydlophosphamide. Cytoxan. Neosar 14 3D 191 Chlorotnianiene. TACE 0 0 0 Cytarabine . Cytosar- U 459271 54...Cyroxan. Neosar 5W Chiorotrianisene. TACE 0 Cytarabine . Cytosar-U 0 Diethylstilbestrol, Stilphostrol 3 Dacarbazine. DTIC-Dome 0 Estradiol, Estrace 1

  11. Factors influencing the choice of specialty of Australian medical graduates.

    PubMed

    Harris, Mary G; Gavel, Paul H; Young, Jeannette R

    2005-09-19

    To identify the relative importance of extrinsic determinants of doctors' choice of specialty. A self-administered postal questionnaire. Australian vocational training programs. 4259 Australian medical graduates registered in September 2002 with one of 16 Australian clinical colleges providing vocational training programs. Choice of specialist vocational training program; extrinsic factors influencing choice of program, and variation by sex, age, marital status and country of birth. In total, 79% of respondents rated "appraisal of own skills and aptitudes" as influential in their choice of specialty followed by "intellectual content of the specialty" (75%). Extrinsic factors rated as most influential were "work culture" (72%), "flexibility of working arrangements" (56%) and "hours of work" (54%). We observed variation across training programs in the importance ascribed to factors influencing choice of specialty, and by sex, age and marital status. Factors of particular importance to women, compared with men, were "appraisal of domestic circumstances" (odds ratio [OR], 1.9), "hours of work" (OR, 1.8) and "opportunity to work flexible hours" (OR, 2.6). Partnered doctors, compared with single doctors, rated "hours of work" and "opportunity to work flexible hours" as more important (OR, 1.3), while "domestic circumstances" was more important to doctors with children than those without children (OR, 1.7). In total, 80% of doctors had chosen their specialty by the end of the third year after graduation. Experience with discipline-based work cultures and working conditions occurs throughout medical school and the early postgraduate years, and most doctors choose their specialty during these years. It follows that interventions to influence doctors' choice of specialty need to target these critical years.

  12. [The influencing factors on alienation in high school students].

    PubMed

    Lee, Eun-Sook

    2004-02-01

    This study was performed to identify the influencing factors on alienation among high school students. Data was collected by questionnaires from 550 students of academic and vocational high schools in G city. The data was analyzed using descriptive statistics, pearson correlation coefficients, and stepwise multiple regression. The scores of alienation among students in financially lower middle class and lower class were higher than those of the upper middle class students, resulting in significant differences(F=6.87, p=.00). A sense of alienation showed a significantly negative correlation with the scores of responding parenting style(r=-.32), family cohesion(r=-.33), school attachment(r=-.51), academic performance(r=-.34), peer relationships(r=-.38), self-control (r=-.43), and social skills(r=-.33). The most powerful predictor of alienation among high school students was school attachment and the variance explained was 26%. A combination of school attachment, self control, peer relationships, family cohesion, demanding parenting style, and academic performance account for 40% of the variance in alienation among high school students. This study suggests that school attachment, self control, peer relationships, family cohesion, demanding parenting style, and academic performance are significant influencing factors on alienation in high school students. Therefore, nursing strategy is needed to manage these revealed factors.

  13. Factors influencing social distance toward people with mental illness.

    PubMed

    Lauber, Christoph; Nordt, Carlos; Falcato, Luis; Rössler, Wulf

    2004-06-01

    When identifying ways to reduce stigmatization because of mental illness it is crucial to understand contributing factors. Social distance-the willingness to engage in relationships of varying intimacy with a person--is an indicator of public attitudes toward persons with mental illness. Multiple linear regression analysis of the results of a vignette-based opinion survey conducted on a representative population sample in Switzerland (n = 594). The level of social distance increases if situations imply 'social closeness.' The vignette describing a person with schizophrenia, attitudes to general aspects of mental health (lay helping, community psychiatry), emotions toward those affected, and the attitude toward consequences of mental illness (medical treatment, medication side effects, negative sanctions, e.g. withdrawal of the driver license) were found to predict social distance. Demographic factors such as age, gender, and the cultural background influence social distance. The explained variance (R2) is 44.8%. Social distance is a multifaceted concept influenced by, e.g., socio-economic and cultural factors, but also by the respondent's general attitude toward (mental) health issues. These results suggest that more knowledge about mental illnesses, especially schizophrenia, may increase social distance. The findings presented here may help to focus anti-stigma campaigns not only on transmission of knowledge, but on integrating different approaches.

  14. Expecting success: Factors influencing ninth graders' science self-efficacy

    NASA Astrophysics Data System (ADS)

    Donahue, Elizabeth

    What factors influence ninth grade students' expectations for success in science? Using social cognitive theory and bioecological systems theory as theoretical frameworks, this dissertation employs data from the High School Longitudinal Study of 2009 (HSLS:09) to examine the relative impact of teacher practices and their perceived attitudes on students' science self-efficacy. Further, as they relate to this broader issue, the relative impact of student subjective task value and teacher characteristics is also investigated. It has been well documented that U.S. students are not achieving at satisfactory levels in science. Education policy has focused on improving science teacher quality as one way to address this problem. Teacher effectiveness has been primarily measured by student achievement on standardized tests. However, not enough attention has been given to the social cognitive factors that can lead to increased achievement and persistence in science as well as how teachers may influence these factors. This study interrogates the relationship between student and teacher variables and the social cognitive construct of self-efficacy, which has proven to have a significant impact on student achievement and persistence in science. Findings add to the current literature surrounding ways that educators may increase student performance in science by employing policies and practices that benefit the development of student science self-efficacy.

  15. Factors Influencing Pediatrician Retirement: A Survey of American Academy of Pediatrics Chapter Members.

    PubMed

    Rimsza, Mary E; Ruch-Ross, Holly; Simon, Harold K; Pendergass, Thomas W; Mulvey, Holly J

    2017-09-01

    To assess the factors that may influence physicians' desire to retire through an analysis of data collected through the American Academy of Pediatrics (AAP) State Pediatrician Workforce Survey. An electronic survey was sent to retired and nonretired US pediatricians who held AAP membership. The respondents were asked about the importance of 12 factors that would influence or had influenced their decision to retire. The physicians who were not yet retired also were asked: "If you could afford to today, would you retire from medicine?" The survey was completed by 8867 pediatricians. Among the nonretired respondents, 27% reported that they would retire today if it were affordable. Increasing regulation of medicine, decreasing clinical autonomy, and insufficient reimbursement were rated as very important factors by >50% of these pediatricians. Among retired pediatricians, 26.9% identified the effort to keep up with clinical advances and changes in practice as a very important factor in their decision to retire. Younger physicians were significantly more likely to rate maintenance of certification requirements, insufficient reimbursement, lack of professional satisfaction, and family responsibilities as very important factors. Rural pediatricians were more interested in retiring than those working in academic settings. There were no sex differences. Twenty-seven percent of pediatricians in practice today would retire today if it were affordable. Identifying and addressing the important factors that influence a pediatrician's desire to retire can potentially reduce the retirement rate of pediatricians and thus increase access to care for children. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Factors influencing return to work after hip and knee replacement.

    PubMed

    Malviya, A; Wilson, G; Kleim, B; Kurtz, S M; Deehan, D

    2014-09-01

    Return to employment is one of the key goals of joint replacement surgery in the working-age population. There is limited quantitative and qualitative research focusing on return to work after hip and knee replacement. It remains unclear why certain groups of patients are not able to achieve sufficient functional improvement to allow productive return to work while others can. Very little is known about the individual patient and employer perspectives in this regard. To review current evidence for the factors influencing employment outcomes in patients undergoing hip and knee replacement. Original articles and reviews in Medline, Embase and PsycINFO from 1987 to 2013 were included in the analysis. Age, patient motivation, employment before surgery and type of job were found to be important factors in determining return to work following hip and knee replacement. There is a need for further qualitative work on how and why these factors influence employment outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Factors Influencing Federal Employee Worker Satisfaction: A Baseline Study.

    ERIC Educational Resources Information Center

    Schmidt, Wallace V.; And Others

    Utilizing data from the Federal Employee Attitude Survey, 1979, a survey was distributed to a stratified random sample of 20,000 employees to identify and analyze the factors influencing federal employee worker satisfaction. Questions on the survey ranged from demographics to personal evaluations of the work environment as recorded on a…

  18. Factors Influencing Knowledge Creation and Innovation in an Organisation

    ERIC Educational Resources Information Center

    Merx-Chermin, Mireille; Nijhof, Wim, J.

    2005-01-01

    Purpose: The purpose of this study is to gain a better understanding of the factors that influence the innovative power of organisations. The concept of innovation and innovative power was examined by analysing the relationship between the construct of the learning organisation, knowledge organisation and innovative organisation, and has resulted…

  19. Environmental Volunteers: Factors Influencing Their Involvement in Environmental Action

    ERIC Educational Resources Information Center

    Liarakou, Georgia; Kostelou, Eleni; Gavrilakis, Costas

    2011-01-01

    The aim of the present study was to investigate the factors that influence volunteers to become involved in environmental action. The research focused on volunteers undertaking action in summer camps organised by an environmental non-governmental organisation (NGO) in Greece. The results suggest that the environmental issues addressed in volunteer…

  20. Factors Influencing BI Data Collection Strategies: An Empirical Investigation

    ERIC Educational Resources Information Center

    Ramakrishnan, Thiagarajan

    2010-01-01

    The purpose of this dissertation is to examine the external factors that influence an organizations' business intelligence (BI) data collection strategy when mediated by BI attributes. In this dissertation, data warehousing strategies are used as the basis on which to frame the exploration of BI data collection strategies. The attributes include…

  1. Factors Influencing Females' Access to the High School Principalship

    ERIC Educational Resources Information Center

    Kruse, Rae Ann

    2012-01-01

    Scope and Method of Study: The purpose of this study was to identify the factors influencing females' access to the Oklahoma secondary school principalship. Although in the United States federal laws and policies are in place to promote equity, research indicates females are underrepresented in secondary school administration. Regardless of equity…

  2. Consumers with Major Depressive Disorder: Factors Influencing Job Placement

    ERIC Educational Resources Information Center

    Hergenrather, Kenneth C.; Haase, Eileen; Zeglin, Robert J.; Rhodes, Scott D.

    2013-01-01

    The theory of planned behavior (TPB) was applied to study the factors that influence the intention of public rehabilitation placement professionals to place consumers with major depressive disorder (MDD) in jobs. A sample of 108 public rehabilitation placement professionals in the Mid-Atlantic region of the United States completed the MDD…

  3. Background factors related to and/or influencing occupation in mentally disordered offenders.

    PubMed

    Lindstedt, Helena; Ivarsson, Ann-Britt; Söderlund, Anne

    2006-09-01

    Knowledge of background and occupational related factors of mentally disordered offenders are missing. It is essential to understand these issues when planning discharge from forensic psychiatric hospital care to enable community dwelling. One aim was to investigate mentally disordered offenders' background factors, confidence in and how they value occupations. Another aim was to investigate MDOs background factors' in relation to and the influences on Occupational Performance and Social Participation. Data was collected with an explorative, correlative design after informed consent, from 74 mentally disordered offenders (mean age 34,2) cared for in forensic psychiatric hospitals. Assessments were Allen Cognitive Level Screen, Capability to Perform Daily Occupations, Interview Schedule of Social Interaction, Manchester Short Assessment of Quality of Life, Self-efficacy Scale and Importance scale. Eight background factors were assembled from the individual forensic psychiatric investigation. Most of the investigated background factors relate to and half of them influence occupational performance, particular the cognitive aspect of occupational performance. The influences on occupation originate from adulthood, such as suffering from schizophrenia, psycho/social problems, and having performed violent crimes. These findings indicate that staff in forensic hospital care should initiate rehabilitation with knowledge about MDOs' complex daily occupations. For avoiding information bias, information gathering preceding treatment planning should be performed in collaboration between caring staff and mentally disordered offenders.

  4. Initiation of sexual intercourse among middle school adolescents: the influence of psychosocial factors.

    PubMed

    Santelli, John S; Kaiser, Javaid; Hirsch, Lesley; Radosh, Alice; Simkin, Linda; Middlestadt, Susan

    2004-03-01

    To explore potential psychosocial predictors for initiation of sexual intercourse among middle-school, inner-city youth, using longitudinal data from the Healthy and Alive! project. We conducted hierarchical, logistic regression with adjustment for intraclass correlation over two sequential periods, including seventh and eighth grades (N = 3163), to assess the independent influence of psychosocial and demographic factors. Internally reliable scales to assess psychosocial influences were created, based on major theories of behavior. The sample was 52% female, 51% black, 30% Hispanic, 9% white, and 3% Asian. At baseline, 13% of girls and 39% of boys reported already having initiated sexual intercourse. Personal and perceived peer norms about refraining from sex were a strong and consistent protective factor. Alcohol and other drug use, poor academic performance, male gender, and black race were consistent risk factors. Self-efficacy showed a mixed effect: protective in the seventh grade but increasing risk in the eighth grade. Speaking a language other than English was a protective factor in seventh grade. Both psychosocial and demographic factors provided independent explanatory power. Psychosocial factors, particularly norms about having sex, influence initiation of sexual intercourse. These data suggest that programs to delay initiation of sexual intercourse should reinforce norms about refraining from sex.

  5. Factors influencing quality of life (QOL) for Korean patients with rheumatoid arthritis (RA).

    PubMed

    Cho, Soo-Kyung; Kim, Dam; Jun, Jae-Bum; Bae, Sang-Cheol; Sung, Yoon-Kyoung

    2013-01-01

    The aim of the study was to identify factors influencing the health-related quality of life (HR-QOL) for Korean RA patients and factors associated with each dimension of the EQ-5D. Two hundred and twenty-five RA patients were recruited from one University Hospital in Seoul, South Korea. Their clinical and socio-demographic data were widely collected by means of interviews, self-administered questionnaires, and clinical examinations. Multiple logistic regression analyses were performed to determine the factors influencing QOL and factors associated with each dimension of the EQ-5D. The mean EQ-5D utility observed for Korean RA patients was 0.60 (-0.29 to 1.0). Functional disability measured with Health Assessment Questionnaire (OR = 10.0, CI 2.8-34.5), disease activity score (DAS) 28 (OR = 2.6, CI 1.4-4.9), and pain VAS (OR = 2.2, CI 1.2-4.1) was three main factors influencing on QOL of RA patients. Although the functional disability consistently showed significant associations with all dimensions, various factors were associated with the each five specific dimension of EQ-5D. Pain (OR = 2.5, CI 1.4-4.6), history of hospitalization (OR = 2.1, CI 1.0-4.3), and men (OR = 2.6, CI 1.0-6.8) were associated with lower QOL in mobility. Use of alternative medicine (OR = 2.0, CI 1.1-3.7) and disease activity (OR = 3.1, CI 1.7-5.7) were associated with lower self-care QOL. For the patients with discomfort in usual activity, pain (OR = 4.7, CI 2.4-9.2) and the presence of anemia (OR = 2.3, CI 1.2-4.5) were major influencing factors. Higher disease activity (OR = 4.5, CI 1.0-21.2) and pain (OR = 3.3, CI 1.9-5.8) were associated with the pain/discomfort dimension of EQ-5D, and the pain (OR = 3.3, CI 1.9-5.8) was an independent associating factor of anxiety/depression. The strongest determinants of lower QOL in Korean RA patients were functional disability, higher disease activity, and subjective pain. However, various factors are influencing on the QOL for RA patients according

  6. Factors influencing cost-related nonadherence to medication in older adults: a conceptually based approach.

    PubMed

    Zivin, Kara; Ratliff, Scott; Heisler, Michele M; Langa, Kenneth M; Piette, John D

    2010-01-01

    Although multiple noncost factors likely influence a patient's propensity to forego treatment in the face of cost pressures, little is known about how patients' sociodemographic characteristics, physical and behavioral health comorbidities, and prescription regimens influence cost-related nonadherence (CRN) to medications. We sought to determine both financial and nonfinancial factors associated with CRN in a nationally representative sample of older adults. We used a conceptual model developed by Piette and colleagues that describes financial and nonfinancial factors that could increase someone's risk of CRN, including income, comorbidities, and medication regimen complexity. We used data from the 2004 wave of the Health and Retirement Study and the 2005 HRS Prescription Drug Study to examine the influence of factors within each of these domains on measures of CRN (including not filling, stopping, or skipping doses) in a nationally representative sample of Americans age 65+ in 2005. Of the 3071 respondents who met study criteria, 20% reported some form of CRN in 2005. As in prior studies, indicators of financial stress such as higher out-of-pocket payments for medications and lower net worth were significantly associated with CRN in multivariable analyses. Controlling for these economic pressures, relatively younger respondents (ages 65-74) and depressive symptoms were consistent independent risk factors for CRN. Noncost factors influenced patients' propensity to forego treatment even in the context of cost concerns. Future research encompassing clinician and health system factors should identify additional determinants of CRN beyond patients' cost pressures.

  7. Influence of factors on release of antimicrobials from antimicrobial packaging materials.

    PubMed

    Wu, Yu-Mei; Wang, Zhi-Wei; Hu, Chang-Ying; Nerín, Cristina

    2018-05-03

    Antimicrobial packaging materials (films or coatings) (APMs) have aroused great interest among the scientists or the experts specialized in material science, food science, packaging engineering, biology and chemistry. APMs have been used to package the food, such as dairy products, poultry, meat (e.g., beef), salmon muscle, pastry dough, fresh pasta, bakery products, fruits, vegetables and beverages. Some materials have been already commercialized. The ability of APMs to extend the shelf-life of the food depends on the release rate of the antimicrobials (AMs) from the materials to the food. The optimum rate is defined as target release rate (TRR). To achieve TRR, the influencing factors of the release rate should be considered. Herein we reviewed for the first time these factors and their influence on the release. These factors mainly include the AMs, food (or food simulant), packaging materials, the interactions among them, the temperature and environmental relative humidity (RH).

  8. Factors Influencing Successful Prescribing by Intern Doctors: A Qualitative Systematic Review

    PubMed Central

    R. Hansen, Christina; Bradley, Colin P.; Sahm, Laura J.

    2016-01-01

    As the majority of prescribing in hospital is undertaken by intern doctors, the aims of this systematic review were to compile the evidence of the qualitative literature on the views and experiences of intern doctors and to examine the role of the pharmacist in assisting in prescribing by interns. A systematic review of the qualitative literature was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The findings were synthesized using thematic analysis. Seven publications were included. Factors influencing prescribing behaviour were related to the environment; collaboration in medical teams; hierarchical structures; and patient and individual factors. This review confirmed that interns’ prescribing behaviour is influenced by multiple factors, and further highlighted the need for an educational intervention that supports the intern completing the prescribing task in a complex environment, and not just addresses the presumed knowledge gap(s). PMID:28970397

  9. Factors Influencing Successful Prescribing by Intern Doctors: A Qualitative Systematic Review.

    PubMed

    R Hansen, Christina; Bradley, Colin P; Sahm, Laura J

    2016-08-24

    As the majority of prescribing in hospital is undertaken by intern doctors, the aims of this systematic review were to compile the evidence of the qualitative literature on the views and experiences of intern doctors and to examine the role of the pharmacist in assisting in prescribing by interns. A systematic review of the qualitative literature was done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The findings were synthesized using thematic analysis. Seven publications were included. Factors influencing prescribing behaviour were related to the environment; collaboration in medical teams; hierarchical structures; and patient and individual factors. This review confirmed that interns' prescribing behaviour is influenced by multiple factors, and further highlighted the need for an educational intervention that supports the intern completing the prescribing task in a complex environment, and not just addresses the presumed knowledge gap(s).

  10. Perceived influence of intrinsic/extrinsic factors on participation in life activities after spinal cord injury.

    PubMed

    Cobb, John E; Leblond, Jean; Dumont, Frédéric S; Noreau, Luc

    2018-04-03

    Various types of limitations on community participation are experienced by people with spinal cord injury (SCI). To determine: 1) the perceived influence of six intrinsic/extrinsic factors (i.e. physical impairment, emotional condition, thinking skills, environment, lack of assistance, discrimination) on participation in 26 life activities, 2) if this influence varied based on extent of participation, and 3) if personal or environmental characteristics influenced perceptions. Secondary analysis of a cohort (SCI Community Survey, n = 1508) using the SCI Person-Perceived Participation in Daily Activities Questionnaire. Frequency tables, Fisher's exact tests and correspondence analyses. Respectively, 79.6% and 38.5% of respondents perceived that their physical impairment and the natural and/or built environment were the main factors that limited participation across all activities. Considering participation between three groups (no participation; less than wanted; as much as wanted), significant differences (p < 0.001) of perceptions were observed in 65% of the combinations (26 activities x 6 factors). The hypothesis that respondents who did not participate would perceive the highest proportion of limitations was confirmed in 41% of the combinations. Perceived influence of the intrinsic/extrinsic factors on participation was not significantly influenced by other personal or environmental characteristics. A majority of people with SCI perceived that their participation is limited by one or more of intrinsic/extrinsic factors. Perceptions regarding which factors influence participation differ between activities and these perceptions appear related to the extent of participation suggesting that those who actively participate could be the most sensitive to limitations in certain activities. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Genetic and environmental factors interact to influence anxiety.

    PubMed

    Gross, Cornelius; Hen, René

    2004-01-01

    Both genetic and environmental factors influence normal anxiety traits as well as anxiety disorders. In addition it is becoming increasingly clear that these factors interact to produce specific anxiety-related behaviors. For example, in humans and in monkeys mutations in the gene encoding for the serotonin transporter result in increased anxiety in adult life when combined with a stressful environment during development. Another recent example comes from twin studies suggesting that a small hippocampus can be a predisposing condition that renders individuals susceptible to post traumatic stress disorder. Such examples illustrate how specific mutations leading to abnormal brain development may increase vulnerability to environmental insults which may in turn lead to specific anxiety disorders.

  12. Social and Environmental Factors Influencing In-Prison Drug Use

    ERIC Educational Resources Information Center

    Woodall, James

    2012-01-01

    Purpose: There is a strong political imperative to regard the prison as a key social setting for health promotion, but evidence indicates that drug misuse continues to be a significant issue for many prisoners. This paper aims to examine the social and environmental factors within the setting that influence individuals' drug taking.…

  13. Factors Influencing Consent to Having Videotaped Mental Health Sessions

    ERIC Educational Resources Information Center

    Ko, Kenton; Goebert, Deborah

    2011-01-01

    Objective: The authors critically reviewed the literature regarding factors influencing consent to having videotaped mental health sessions. Methods: The authors searched the literature in PubMed, PsycINFO, Google Scholar, and Web of Science from the mid-1950s through February 2009. Results: The authors identified 27 studies, of which 19 (73%)…

  14. Factors Influencing Secondary School Teachers' Adoption of Teaching Blogs

    ERIC Educational Resources Information Center

    Lai, Hui-Min; Chen, Chin-Pin

    2011-01-01

    Recently, there has been a significant proliferation in the number of teaching blogs; however, little has been explored about what motivates teachers to adopt teaching blogs. The purpose of this study is to find out which factors can significantly influence teacher decisions regarding their teaching blog adoption and the relative importance of…

  15. Survey of factors influencing learner engagement with simulation debriefing among nursing students.

    PubMed

    Roh, Young Sook; Jang, Kie In

    2017-12-01

    Simulation-based education has escalated worldwide, yet few studies have rigorously explored predictors of learner engagement with simulation debriefing. The purpose of this cross-sectional, descriptive survey was to identify factors that determine learner engagement with simulation debriefing among nursing students. A convenience sample of 296 Korean nursing students enrolled in the simulation-based course completed the survey. A total of five instruments were used: (i) Characteristics of Debriefing; (ii) Debriefing Assessment for Simulation in Healthcare - Student Version; (iii) The Korean version of the Simulation Design Scale; (iv) Communication Skills Scale; and (v) Clinical-Based Stress Scale. Multiple regression analysis was performed using the variables to investigate the influencing factors. The results indicated that influencing factors of learning engagement with simulation debriefing were simulation design, confidentiality, stress, and number of students. Simulation design was the most important factor. Video-assisted debriefing was not a significant factor affecting learner engagement. Educators should organize and conduct debriefing activities while considering these factors to effectively induce learner engagement. Further study is needed to identify the effects of debriefing sessions targeting learners' needs and considering situational factors on learning outcomes. © 2017 John Wiley & Sons Australia, Ltd.

  16. Factors that influence Asian communities' access to mental health care.

    PubMed

    Wynaden, Dianne; Chapman, Rose; Orb, Angelica; McGowan, Sunita; Zeeman, Zenith; Yeak, SiewHo

    2005-06-01

    This paper presents the findings of a qualitative study to identify factors that influence Asian communities' access to mental health care and how mental health care is delivered to them. Semistructured interviews were completed with Asian community members/leaders and health-care professionals. Content analysis identified major themes. Participants also completed a demographic data sheet. The research aimed to provide health professionals with an increased understanding of the values and beliefs held by people from Asian communities regarding the cause and treatment of mental illness. Data analysis identified six main themes that influenced Asian communities' access to mental health care and how mental health care is delivered to them. They were: shame and stigma; causes of mental illness; family reputation; hiding up; seeking help; and lack of collaboration. The findings highlighted that people from Asian communities are unwilling to access help from mainstream services because of their beliefs, and that stigma and shame are key factors that influence this reluctance. The findings also highlight that the mental health needs of refugee women are significant, and that they comprise a vulnerable group within Australian society.

  17. Protective effect of β-D-glucan and glutamine on the genomic instability induced by Cytarabine/Ara-C in BALB/c mice.

    PubMed

    de Souza Silva, Priscilla Mirian; de Sousa, Raimundo Vicente; Simão, Anderson Assaid; Cesar, Pedro Henrique Souza; Trento, Marcus Vinicius Cardoso; Marcussi, Silvana

    2018-05-28

    Prophylactic antibiotics and growth promoters have been substituted, mainly for livestock, by immunomodulators and intestinal health promoters - such as β-D-glucans and glutamine. The aim of this study was to verify the beneficial effects of β-D-glucans and glutamine against Cytarabine/Ara-C, evaluating the DNA damage in leukocytes, the leukogram, and the mitotic index of intestinal crypts cells. Balb/C mice received treatment with β-D-glucan (80 mg/Kg), glutamine (150 mg/Kg), or both, for 21 days. On the last two days of this period, Ara-C was administered (1.8 mg/animal) by intraperitoneal injection every 12 h. The animals submitted to the treatment with Ara-C presented the highest genotoxic index, a significant leukopenia, and a decrease in the mitotic index of the intestinal crypts cells. Treatment with β-D-glucan protected the leukocytes against DNA fragmentation induced by Ara-C. Glutamine alone promoted maintenance of the mitotic index and, in association with β-Dglucan, reduced leukopenia. Thus, the use of β-D-glucan and glutamine proved to be beneficial to intestinal tropism. This can happen once the damage to the genetic material, prevented by the treatments with β-D-glucan and glutamine, can result in genotoxicity. Not only this, but it might be capable of turning into a mutagenesis, with consequential physiopathological alterations. Copyright © 2018. Published by Elsevier B.V.

  18. Proximate and landscape factors influence grassland bird distributions

    USGS Publications Warehouse

    Cunningham, M.A.; Johnson, D.H.

    2006-01-01

    Ecologists increasingly recognize that birds can respond to features well beyond their normal areas of activity, but little is known about the relative importance of landscapes and proximate factors or about the scales of landscapes that influence bird distributions. We examined the influences of tree cover at both proximate and landscape scales on grassland birds, a group of birds of high conservation concern, in the Sheyenne National Grassland in North Dakota, USA. The Grassland contains a diverse array of grassland and woodland habitats. We surveyed breeding birds on 2015 100 m long transect segments during 2002 and 2003. We modeled the occurrence of 19 species in relation to habitat features (percentages of grassland, woodland, shrubland, and wetland) within each 100-m segment and to tree cover within 200-1600 m of the segment. We used information-theoretic statistical methods to compare models and variables. At the proximate scales, tree cover was the most important variable, having negative influences on 13 species and positive influences on two species. In a comparison of multiple scales, models with only proximate variables were adequate for some species, but models combining proximate with landscape information were best for 17 of 19 species. Landscape-only models were rarely competitive. Combined models at the largest scales (800-1600 m) were best for 12 of 19 species. Seven species had best models including 1600-m landscapes plus proximate factors in at least one year. These were Wilson's Phalarope (Phalaropus tricolor), Sedge Wren (Cistothorus platensis), Field Sparrow (Spizella pusilla), Grasshopper Sparrow (Ammodramus savannarum), Bobolink (Dolychonix oryzivorus), Red-winged Blackbird (Agelaius phoeniceus), and Brown-headed Cowbird (Molothrus ater). These seven are small-bodied species; thus larger-bodied species do not necessarily respond most to the largest landscapes. Our findings suggest that birds respond to habitat features at a variety of

  19. Factors Influencing Right Hemisphere Engagement During Metaphor Comprehension

    PubMed Central

    Diaz, Michele T.; Eppes, Anna

    2018-01-01

    Although the left hemisphere is critical for language, clinical, behavioral, and neuroimaging research suggest that the right hemisphere also contributes to language comprehension. In particular, research has suggested that figurative language may be one type of language that preferentially engages right hemisphere regions. However, there is disagreement about whether these regions within the right hemisphere are sensitive to figurative language per se or to other factors that co-vary with figurativeness. In this article, we will review the neuroimaging literature on figurative language processing, focusing on metaphors, within the context of several theoretical perspectives that have been proposed about hemispheric function in language. Then we will examine three factors that may influence right hemisphere engagement: novelty, task difficulty, and context. We propose that factors that increase integration demands drive right hemisphere involvement in language processing, and that such recruitment is not limited to figurative language. PMID:29643825

  20. [Comparison of the factors influencing young adolescents' aggression according to family structure].

    PubMed

    Yun, Eun Kyoung; Shin, Sung Hee

    2013-06-01

    This cross-sectional study was done to compare factors influencing young adolescents' aggression according to family structure. Participants were 680 young adolescents aged 11 to 15 years (113 in single father families, 136 in single mother families, 49 in grandparent families, and 382 in both-parent families). All measures were self-administered. Data were analyzed using SPSS 18.0 program and factors affecting young adolescents' aggression were analyzed by stepwise multiple regression. Levels of young adolescents' aggression and all variables were significantly different among the four family structure groups. Factors influencing young adolescents' aggression were also different according to these 4 groups. For single father families, depression-anxiety and family hardiness significantly predicted the level of young adolescents' aggression (adjusted R square=.37, p<.001). For single mother families, depression-anxiety, gender, and friends' support significantly predicted the level of young adolescents' aggression (adjusted R square=.58, p<.001). For grandparent families, depression-anxiety and family support significantly predicted the level of young adolescents' aggression (adjusted R square=.58, p<.001). For both-parent families, depression-anxiety, family hardiness, and friends' support significantly predicted the level of young adolescents' aggression (adjusted R square=.48, p<.001). Nurses working with young adolescents should consider family structure-specific factors influencing aggression in this population.

  1. Primary care specialty career choice among Canadian medical students: Understanding the factors that influence their decisions.

    PubMed

    Osborn, Heather Ann; Glicksman, Jordan T; Brandt, Michael G; Doyle, Philip C; Fung, Kevin

    2017-02-01

    To identify which factors influence medical students' decision to choose a career in family medicine and pediatrics, and which factors influence their decision to choose careers in non-front-line specialties. Survey that was created based on a comprehensive literature review to determine which factors are considered important when choosing practice specialty. Ontario medical school. An open cohort of medical students in the graduating classes of 2008 to 2011 (inclusive). The main factors that influenced participants' decision to choose a career in primary care or pediatrics, and the main factors that influenced participants' decision to choose a career in a non-front-line specialty. A total of 323 participants were included in this study. Factors that significantly influenced participants' career choice in family medicine or pediatrics involved work-life balance (acceptable hours of practice [ P = .005], acceptable on-call demands [ P = .012], and lifestyle flexibility [ P = .006]); a robust physician-patient relationship (ability to promote individual health promotion [ P = .014] and the opportunity to form long-term relationships [ P  < .001], provide comprehensive care [ P = .001], and treat patients and their families [ P = .006]); and duration of residency program ( P = .001). The career-related factors that significantly influenced participants' decision to choose a non-front-line specialty were as follows: becoming an expert ( P  < .001), maintaining a focused scope of practice ( P  < .001), having a procedure-focused practice ( P = .001), seeing immediate results from one's actions ( P  < .001), potentially earning a high income ( P  < .001), and having a perceived status among colleagues ( P  < .001). In this study, 8 factors were found to positively influence medical students' career choice in family medicine and pediatrics, and 6 factors influenced the decision to choose a career in a non-front-line specialty. Medical students can be

  2. [Endocrine factors influencing melanoma progression].

    PubMed

    Dobos, Judit

    2009-03-01

    According to recent findings that beside cancers traditionally considered as hormone-dependent, several other tumor types show different behavior in the two sexes, indicating the possible role of endocrine factors in the course of these diseases. The possibility that endocrine factors may influence the clinical course of human malignant melanoma is suggested by the higher survival rate in premenopausal vs. postmenopausal women or men of any ages. However, investigations on the sex hormone receptor status of human cutaneous melanomas and experiments attempting to support the epidemiological results yielded conflicting results. In our human melanoma cell lines we failed to detect steroid receptors at protein level, while quantitative PCR demonstrated that their mRNA expression level was orders of magnitude lower compared to the positive control cell lines. Sex hormones did not influence the in vitro features of the human melanoma cells considerably. On the other hand, glucocorticoid receptor was present both at mRNA and protein level, although dexamethasone was effective in vitro only at high doses. Our previous experiments showed that intrasplenic injection of human melanoma cells resulted in a significantly higher number of liver colonies in male than in female SCID mice. We now show that this difference evolves during the first day. After injection into the tail vein we did not observe gender-dependent difference in the efficiency of pulmonary colonization. Examining the pattern of metastasis formation after intracardiac injection, we have found differences between the two sexes in the incidence or number of colonies only in the case of the liver but not in other organs. We concluded that the observed phenomenon is specific to the liver; therefore we investigated the effects of 2-methoxyestradiol, an endogenous metabolite of estradiol produced mainly in the liver, with an estrogen receptor-independent antitumor activity. 2ME2 effectively inhibited melanoma cell

  3. Successful use of full-dose dexamethasone, high-dose cytarabine, and cisplatin as part of initial therapy in non-hodgkin and hodgkin lymphoma with severe hepatic dysfunction.

    PubMed

    McCarthy, Jeanne; Gopal, Ajay K

    2009-04-01

    Anthracycline-based chemotherapy is the cornerstone of modern curative regimens for aggressive lymphomas; however, these drugs cannot be safely administered in the setting of severe hepatic dysfunction. Alternative regimens for this setting are required. We describe 2 patients with newly diagnosed advanced aggressive lymphoma (diffuse large B-cell lymphoma [DLBCL] and classic Hodgkin lymphoma [HL]) presenting with severe hepatic dysfunction with hyperbilirubinemia (4.3-13.2 mg/dL). Because of the inability to safely administer unattenuated doses of anthracycline-based regimens, dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was used at full doses (along with rituximab for the DLBCL patient) until hepatic function normalized (1-5 cycles). The treatment was then converted to R-CHOP (rituximab/cyclophosphamide/ doxorubicin/vincristine/prednisone) and ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) for the DLBCL and HL patient, respectively, to complete therapy. The patients had a partial remission and complete remission, respectively. These data suggest that DHAP is a safe and effective regimen that can be used without dose modification as part of initial therapy in the setting of aggressive lymphoma and hepatic failure. The literature on the use of treatment regimens for aggressive lymphoma in the setting of hepatic dysfunction is reviewed.

  4. [Case-control study on influence factors of birth defects].

    PubMed

    Xiu, Xin-hong; Yuan, Li; Wang, Xiao-ming; Chen, Yu-hua; Wan, Ai-hua; Fu, Ping

    2011-07-01

    To investigate the influence factors of birth defects. The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case-control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.). The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6.034‰. The top six defect diseases were congenital heart disease (112 cases), total harelip (cleft lip; cleft lip with palate: 85 cases), polydactyly (53 cases), neural tube defects (38 cases), congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48%, 353/648). (2) Their mother education level in the birth-defect group (25.6%) were significantly lower than that in control group (30.0%, P<0.05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P<0.05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20.5%, respectively) was higher than that in control group (1.1% and 11.7%, respectively), the difference between which were significant (P<0.01). The rate of disease (34.3%), fever (13.1%), taking drugs (33.8%) in pregnancy period in birth defect group were higher than that in control group (13.5%, 1.5% and 9.9%, respectively), the difference between which were significant (P<0.01). The rate

  5. Soil moisture and biogeochemical factors influence the distribution of annual Bromus species

    Treesearch

    Jayne Belnap; John M. Stark; Benjamin M. Rau; Edith B. Allen; Susan Phillips

    2016-01-01

    Abiotic factors have a strong influence on where annual Bromus species are found. At the large regional scale, temperature and precipitation extremes determine the boundaries of Bromus occurrence. At the more local scale, soil characteristics and climate influence distribution, cover, and performance. In hot, dry, summer-rainfall-dominated deserts (Sonoran, Chihuahuan...

  6. Factors influencing reductions in smoking among Australian adolescents.

    PubMed

    Dessaix, Anita; Maag, Audrey; McKenzie, Jeanie; Currow, David C

    2016-01-28

    A continued increase in the proportion of adolescents who never smoke, as well as an understanding of factors that influence reductions in smoking among this susceptible population, is crucial. The World Health Organization Framework Convention on Tobacco Control provides an appropriate structure to briefly examine Australian and New South Wales policies and programs that are influencing reductions in smoking among adolescents in Australia. This paper provides an overview of price and recent tax measures to reduce the demand for tobacco, the evolution of smoke-free environment policies, changes to tobacco labelling and packaging, public education campaigns, and restrictions to curb tobacco advertising. It also discusses supplyreduction measures that limit adolescents' access to tobacco products. Consideration is given to emerging priorities to achieve continued declines in smoking by Australian adolescents.

  7. Factors influencing stakeholders attitudes toward genetically modified aedes mosquito.

    PubMed

    Amin, Latifah; Hashim, Hasrizul

    2015-06-01

    Dengue fever is a debilitating and infectious disease that could be life-threatening. It is caused by the dengue virus which affects millions of people in the tropical area. Currently, there is no cure for the disease as there is no vaccine available. Thus, prevention of the vector population using conventional methods is by far the main strategy but has been found ineffective. A genetically modified (GM) mosquito is among the favoured alternatives to curb dengue fever in Malaysia. Past studies have shown that development and diffusion of gene technology products depends heavily upon public acceptance. The purpose of this study is to identify the relevant factors influencing stakeholders' attitudes toward the GM Aedes mosquito and to analyse the relationships between all the factors using the structural equation model. A survey was carried out on 509 respondents from various stakeholder groups in the Klang Valley region of Malaysia. Results of the survey have confirmed that public perception towards complex issues such as gene technology should be seen as a multi-faceted process. The perceived benefit-perceived risk balance is very important in determining the most predominant predictor of attitudes toward a GM mosquito. In this study the stakeholders perceived the benefit of the GM mosquito as outweighing its risk, translating perceived benefit as the most important direct predictor of attitudes toward the GM mosquito. Trust in key players has a direct influence on attitudes toward the GM mosquito while moral concern exhibited an indirect influence through perceived benefits. Other factors such as attitudes toward technology and nature were also indirect predictors of attitudes toward the GM mosquito while religiosity and engagement did not exhibited any significant roles. The research findings serve as a useful database to understand public acceptance and the social construct of public attitudes towards the GM mosquito to combat dengue.

  8. A preliminary study investigating the factors influencing STEM major selection by African American females

    NASA Astrophysics Data System (ADS)

    Ray, Tiffany Monique

    The purpose of this study was to investigate the significant factors influencing STEM major selection by African American females. A quantitative research design with a qualitative component was employed. Ex post facto survey research was conducted utilizing an online questionnaire to collect data from participants. African American undergraduate females that had declared a major in STEM comprised the target population for the study. As a basis for comparison, a second data collection ensued. All non-African American undergraduate females majoring in STEM also received the survey instrument to determine if there was a significant difference between factors that influence STEM major selection between the two groups. The Social Cognitive Career Choice Model comprised the conceptual framework for this study. Frequencies and percentages illustrated the demographic characteristics of the sample, as well as the average influence levels of each of the items without regard for level of significance. The researcher conducted an independent samples t-test to compare the mean scores for undergraduate African American females majoring in STEM and non-African American females majoring in STEM on each influential factor on the survey instrument. The researcher coded responses to open-ended questions to generate themes and descriptions. The data showed that African American female respondents were very influenced by the following items: specific interest in the subject, type of work, availability of career opportunities after graduation, parent/guardian, precollege coursework in science, and introductory college courses. In addition, the majority of respondents were very influenced by each of the confidence factors. African American females were overwhelmingly not influenced by aptitude tests. African American females were more influenced than their non-African American female counterparts for the following factors: reputation of the university, college or department, high level

  9. Granulocyte-Colony Stimulating Factor (G-CSF) Administration for Chemotherapy-Induced Neutropenia.

    PubMed

    Yalçin, Ş; Güler, N; Kansu, E; Ertenli, I; Güllü, I; Barişta, I; Çelik, I; Kars, A; Tekuzman, G; Baltali, E; Firat, D

    1996-01-01

    This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm(3) for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G-CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia.

  10. Factors That Influence the Recruitment and Retention of Nurses in Public Health Agencies.

    PubMed

    Yeager, Valerie A; Wisniewski, Janna M

    Given challenges to recruiting nurses to public health and the growth in national policies focused on population health, it is crucial that public health agencies develop strategies to sustain this important group of employees. The objective of this study was to examine factors that influence nurses' decisions to work in public health agencies. This cross-sectional study examined perspectives of nurses who worked in state and local public health departments and responded to the 2010 Council on Linkages Between Academia and Public Health Practice's survey of public health workers. We calculated the mean rating of each recruitment and retention factor for nurses and non-nurses separately and compared differences by using t tests. We then used multivariate regression analysis to examine differences in ratings by role (ie, nurse or non-nurse). After controlling for personal and organizational characteristics, the influence of 5 recruitment factors was significantly stronger among nurses than among non-nurses: flexibility of work schedule ( P < .001), autonomy/employee empowerment ( P < .001), ability to innovate ( P = .002), specific duties and responsibilities ( P = .005), and identifying with the mission of the organization ( P = .02). The influence of 5 retention factors was stronger among nurses than among non-nurses : autonomy/employee empowerment ( P < .001), flexibility of work schedule ( P < .001), specific duties and responsibilities ( P < .001), opportunities for training/continuing education ( P = .03), and ability to innovate ( P = .008). Some factors that influence nurses to begin and remain working in local governmental public health agencies, such as flexible schedules and employee autonomy, are factors that governmental public health agencies can design into positions and highlight when recruiting from health care organizations, private industry, and academia.

  11. Health related quality of life and influencing factors among welders.

    PubMed

    Qin, Jingxiang; Liu, Wuzhong; Zhu, Jun; Weng, Wei; Xu, Jiaming; Ai, Zisheng

    2014-01-01

    Occupational exposure to welding fumes is a serious occupational health problem all over the world. Welders are exposed to many occupational hazards; these hazards might cause some occupational diseases. The aim of the study was to assess the health related quality of life (HRQL) of electric welders in Shanghai China and explore influencing factors to HRQL of welders. 301 male welders (without pneumoconiosis) and 305 non-dust male workers in Shanghai were enrolled in this study. Short Form-36 (SF-36) health survey questionnaires were applied in this cross-sectional study. Socio-demographic, working and health factors were also collected. Multiple stepwise regress analysis was used to identify significant factors related to the eight dimension scores. Six dimensions including role-physical (RP), bodily pain (BP), general health (GH), validity (VT), social function (SF), and mental health (MH) were significantly worse in welders compared to non-dust workers. Multiple stepwise regress analysis results show that native place, monthly income, quantity of children, drinking, sleep time, welding type, use of personal protective equipment (PPE), great events in life, and some symptoms including dizziness, discomfort of cervical vertebra, low back pain, cough and insomnia may be influencing factors for HRQL of welders. Among these factors, only sleep time and the use of PPE were salutary. Some dimensions of HRQL of these welders have been affected. Enterprises which employ welders should take measures to protect the health of these people and improve their HRQL.

  12. 5 CFR 919.860 - What factors may influence the debarring official's decision?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... responsibility. In making a debarment decision, the debarring official may consider the following factors: (a... official's decision? 919.860 Section 919.860 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT...) Debarment § 919.860 What factors may influence the debarring official's decision? This section lists the...

  13. Factors Influencing Orthopedic Surgery Residents' Choice of Subspecialty Fellowship.

    PubMed

    Kavolus, Joseph J; Matson, Andrew P; Byrd, William A; Brigman, Brian E

    2017-09-01

    In the setting of increasing student debt, a rapidly changing health care system, and growing transparency in the age of outcome reporting, residents have many factors to consider when determining which fellowship to pursue. An institutional review board-approved link to an online survey was emailed to orthopedic surgery trainees across the United States. Demographics were collected, and 14 fellowship influences were assessed using a Likert scale. A total of 360 responses were received. Of the respondents, 85.5% (n=308) were male and 14.5% (n=52) were female. Responses were received from every region of the United States and from every postgraduate year. Respondents represented the gamut of relationship status and indebtedness. Respondents were interested in all of the current major subspecialties. Pursuit of an intellectually stimulating subspecialty had the highest average Likert score (3.38), followed by variety of cases (3.26). The lowest scores were for residency program with a strong tradition of placing into a particular subspecialty (2.08) and potential to conduct research in that subspecialty (2.09). Marital status, number of children, and level of debt did not significantly affect the importance of factors in selecting a fellowship. Choice of subspecialty did influence the level of importance of various factors. Intellectual stimulation and a strong mentor were the most influential factors in the decision to pursue a given fellowship. Because fellowship is now the norm, it is important to understand the motives behind young orthopedic surgeons' career aspirations. [Orthopedics. 2017; 40(5):e820-e824.]. Copyright 2017, SLACK Incorporated.

  14. Factors influencing neonatal therapeutic effect of anti-MRSA drugs.

    PubMed

    Hayashi, H; Matsuzaki, T; Saito, A; Shimizu, M; Matsumoto, Y

    2005-07-01

    Factors influencing the neonatal therapeutic effect of anti-MRSA (methicillin-resistant Staphylococcus aureus) drugs are investigated. This study took place over a two-year period from April 1998 to March 2000. We calculated the non-adjusted odds ratio for each influential factor to determine the therapeutic effect of anti-MRSA drugs. Significant factors for therapeutic effect were found to be platelet count, urea nitrogen, creatinine, and CRP, each measured before starting administration of anti-MRSA drugs; whether blood drug concentration was measured; and whether pneumonia or septicemia was present. There was a tendency where a better therapeutic effect was gained when the total protein and albumin values were high. We applied multivariate logistic regression analysis to these factors, and found the following independent significant factors: CRP (odds ratio (OR) = 1.582), albumin (OR = 3.079), Cre (OR -0.213), whether blood drug concentration was measured (OR = 3.767), and presence of pneumonia or septicemia (OR = 0.216). This result suggests that consideration should be given to these five important factors when treating MRSA patients.

  15. [Factors influencing research activity of Andalusian nurses and improvement strategies].

    PubMed

    López Alonso, Sergio R; Gálvez González, María; Amezcua, Manuel

    2013-04-01

    To identify factors influencing research activity of Andalusian nurses and to find improvement strategies. Qualitative research using SWOT analysis (weaknesses, threats, strengths, opportunities). Nurses were selected deliberately in eight groups according to predetermined criteria. Analysis included categorization and relationship of factors and strategies. 81 participants were included in groups of 7-12 range. 45 categories were identified with 212 factors: 12 weaknesses (50 factors), 10 strengths (44 factors), 12 threats (68 factors) and 11 opportunities (50 factors). In addition, 32 categories were identified with 53 strategies: 14 categories of W-T strategies (42 strategies), 3 categories of S-T strategies (11 strategies), 5 categories of W-O strategies (13 strategies) and 10 categories of S-O strategies (41 strategies). Nurses identified numerous factors, mainly threats. The strategies are focused on W-T but they also suggest many but weak 5-0 strategies due to the low potential of the opportunities and strengths perceived.

  16. Alteration of Influencing Factors of E-Learning Continued Intention for Different Degrees of Online Participation

    ERIC Educational Resources Information Center

    Chang, Chi-Cheng; Liang, Chaoyun; Shu, Kuen-Ming; Chiu, Yi-Chun

    2015-01-01

    The purpose of the present study was to investigate the variation of influencing factors of e-learning continuance intention for different degrees of participation and to examine moderating effects of degrees of participation on influencing factors of e-learning continuance intention. Participants included 670 learners from an adult professional…

  17. Factors Influencing the Health Behaviour of Indigenous Australians: Perspectives from Support People.

    PubMed

    Waterworth, Pippa; Pescud, Melanie; Braham, Rebecca; Dimmock, James; Rosenberg, Michael

    2015-01-01

    Disparities between the health of Indigenous and non-Indigenous populations continue to be prevalent within Australia. Research suggests that Indigenous people participate in health risk behaviour more often than their non-Indigenous counterparts, and that such behaviour has a substantial impact on health outcomes. Although this would indicate that reducing health risk behaviour may have positive effects on health outcomes, the factors that influence Indigenous health behaviour are still poorly understood. This study aimed to interview people who support Indigenous groups to gain an understanding of their views on the factors influencing health behaviour within Indigenous groups in Western Australia. Twenty nine people participated in the study. The emergent themes were mapped against the social ecological model. The results indicated that: (1) culture, social networks, history, racism, socioeconomic disadvantage, and the psychological distress associated with some of these factors interact to affect health behaviour in a complex manner; (2) the desire to retain cultural identity and distinctiveness may have both positive and negative influence on health risk behaviour; (3) strong social connections to family and kin that is intensified by cultural obligations, appears to affirm and disrupt positive health behaviour; (4) the separation between Indigenous and non-Indigenous social connection/networks that appeared to be fostered by marginalisation and racism may influence the effect of social networks on health behaviour; and (5) communication between Indigenous and non-Indigenous people may be interrupted by distrust between the groups, which reduces the influence of some non-Indigenous sources on the health behaviour of Indigenous people.

  18. Factors Influencing the Health Behaviour of Indigenous Australians: Perspectives from Support People

    PubMed Central

    Waterworth, Pippa; Pescud, Melanie; Braham, Rebecca; Dimmock, James; Rosenberg, Michael

    2015-01-01

    Disparities between the health of Indigenous and non-Indigenous populations continue to be prevalent within Australia. Research suggests that Indigenous people participate in health risk behaviour more often than their non-Indigenous counterparts, and that such behaviour has a substantial impact on health outcomes. Although this would indicate that reducing health risk behaviour may have positive effects on health outcomes, the factors that influence Indigenous health behaviour are still poorly understood. This study aimed to interview people who support Indigenous groups to gain an understanding of their views on the factors influencing health behaviour within Indigenous groups in Western Australia. Twenty nine people participated in the study. The emergent themes were mapped against the social ecological model. The results indicated that: (1) culture, social networks, history, racism, socioeconomic disadvantage, and the psychological distress associated with some of these factors interact to affect health behaviour in a complex manner; (2) the desire to retain cultural identity and distinctiveness may have both positive and negative influence on health risk behaviour; (3) strong social connections to family and kin that is intensified by cultural obligations, appears to affirm and disrupt positive health behaviour; (4) the separation between Indigenous and non-Indigenous social connection/networks that appeared to be fostered by marginalisation and racism may influence the effect of social networks on health behaviour; and (5) communication between Indigenous and non-Indigenous people may be interrupted by distrust between the groups, which reduces the influence of some non-Indigenous sources on the health behaviour of Indigenous people. PMID:26599437

  19. Factors Influencing Career Choice of Management Students in India

    ERIC Educational Resources Information Center

    Agarwala, Tanuja

    2008-01-01

    Purpose: This paper aims to explore the influence of a range of factors on the career choice of management students in India. The importance of different individuals in the family and at work in making career choices among these students is also to be explored. In addition, the study seeks to address the relationship of the cultural values of…

  20. Factors Influencing Students' Decisions about Post-Year 10 Education

    ERIC Educational Resources Information Center

    Beswick, Kim; Hay, Ian; Watson, Jane; Allen, Jeanne; Cranston, Neil

    2012-01-01

    This paper reports pilot data from an instrument devised as part of a large ARC funded project that aims, among other things, to investigate factors that influence the decisions of students in rural and/or disadvantaged areas to continue their schooling beyond Year 10. One section of the pilot student questionnaire comprised 42 items designed to…

  1. Factors Influencing Student Affairs Professionals' Attainment of Professional Competencies

    ERIC Educational Resources Information Center

    Muller, Kristyn; Grabsch, Dustin; Moore, Lori

    2018-01-01

    Limited research exists that examines factors influencing student affairs professionals' attainment of the professional competencies that are expected of them. The study described in this article analyzed student affairs professionals' survey responses to determine which demographics, pre-professional experiences, and educational experiences…

  2. Factors Influencing Implementation of a Preschool-Based Physical Activity Intervention

    ERIC Educational Resources Information Center

    Lau, Erica Y.; Saunders, Ruth P.; Beets, Michael W.; Cai, Bo; Pate, Russell R.

    2017-01-01

    Examining factors that influence implementation of key program components that underlie an intervention's success provides important information to inform the development of effective dissemination strategies. We examined direct and indirect effects of preschool capacity, quality of prevention support system and teacher characteristics on…

  3. Investigation of features in radon soil dynamics and search for influencing factors

    NASA Astrophysics Data System (ADS)

    Yakovlev, Grigorii; Cherepnev, Maxim; Nagorskiy, Petr; Yakovleva, Valentina

    2018-03-01

    The features in radon soil dynamics at two depths were investigated and the main influencing factors were revealed. The monitoring of radon volumetric activity in soil air was performed at experimental site of Tomsk Observatory of Radioactivity and Ionizing Radiation with using radon radiometers and scintillation detectors of alpha-radiation with 10 min sampling frequency. The detectors were installed into boreholes of 0.5 and 1 m depths. The analysis of the soil radon monitoring data has allowed revealing some dependencies at daily and annual scales and main influencing factors. In periods with clearly defined daily radon variations in the soil were revealed the next: 1) amplitude of the daily variations of the soil radon volumetric activity damps with the depth, that is related with the influence of convective fluxes in the soil; 2) temporal shift between times of occurrence of radon volumetric activity maximum (or minimum) values at 0.5 m and 1 m depths can reach 3 hours. In seasonal dynamics of the soil radon the following dependences were found: 1) maximal values are observed in winter, but minimal - in summer; 2) spring periods of snow melting are accompanied by anomaly increasing of radon volumetric activity in the soil up to about 3 times. The main influencing factors are atmospheric precipitations, temperature gradient in the soil and the state of upper soil layer.

  4. Factors influencing risky decision-making in patients with cerebral infarction.

    PubMed

    Gong, Jingjing; Zhang, Yan; Wu, Bing; Feng, Jun; Zhang, Weiwei; Wang, Shijie; Huang, Yonghua; Wu, Xinhuai

    2015-01-01

    Numerous studies have found that the framing effect is common in medical scenarios, but few studies have examined the influence of the framing effect upon thrombolytic therapy for cerebral infarction. In this study, 1040 inpatients and outpatients in the department of neurology were recruited to explore whether there is a framing effect in decision-making within thrombolytic therapy, and if so, which factors influence that effect. The findings from Study 1 indicate that the framing effect occurred in patients both with and without cerebral infarction (χ(2) = 7.90, p = .005; χ(2) = 5.16, p = .023, respectively), with both groups displaying risk-seeking behavior (thrombolytic therapy) in the positive frame and no risk aversion or risk seeking in the negative frame. The results of Study 2 show that the patients preferred risk seeking in both collaborative and individual decision-making. In the collaborative decision-making group, the patients in the senior group showed the framing effect (χ(2) = 5.35, p < .05), with the patients in the positive frame (G) showing more significant risk seeking than both those in the negative frame (H) and those in the other positive frame (A, C, and E). In summary, decision-making about thrombolytic therapy in patients with cerebral infarction is influenced by the framing effect, and some influencing factors should be attended in clinical practice. Further research is necessary to guide the treatment of cerebral infarction.

  5. An Investigation of Factors Influencing Nurses' Clinical Decision-Making Skills.

    PubMed

    Wu, Min; Yang, Jinqiu; Liu, Lingying; Ye, Benlan

    2016-08-01

    This study aims to investigate the influencing factors on nurses' clinical decision-making (CDM) skills. A cross-sectional nonexperimental research design was conducted in the medical, surgical, and emergency departments of two university hospitals, between May and June 2014. We used a quantile regression method to identify the influencing factors across different quantiles of the CDM skills distribution and compared the results with the corresponding ordinary least squares (OLS) estimates. Our findings revealed that nurses were best at the skills of managing oneself. Educational level, experience, and the total structural empowerment had significant positive impacts on nurses' CDM skills, while the nurse-patient relationship, patient care and interaction, formal empowerment, and information empowerment were negatively correlated with nurses' CDM skills. These variables explained no more than 30% of the variance in nurses' CDM skills and mainly explained the lower quantiles of nurses' CDM skills distribution. © The Author(s) 2016.

  6. Audit in general practice: factors influencing participation.

    PubMed Central

    Baker, R.; Robertson, N.; Farooqi, A.

    1995-01-01

    OBJECTIVE--To identify the factors influencing participation in a single topic audit initiated by a medical audit advisory group. DESIGN--Interview and questionnaire survey of general practitioners who had been invited to take part in an audit of vitamin B-12. SETTING--All 147 general practices in Leicestershire. MAIN OUTCOME MEASURES--Aspects of structure, attitude, and behaviour that influenced participation or non-participation. RESULTS--75 practices completed the audit, 49 withdrew after initial agreement, and 23 refused to take part at the outset. Participants were more likely than those who refused to view the advisory group as useful or a threat and to have positive thoughts about audit but less likely to have previously undertaken audit entailing implementation of change. Participants were more likely than those who withdrew to have positive thoughts about audit and to have discussed whether to take part within the practice but were less likely to view the advisory group as useful. The most common reason given for withdrawal was lack of time. CONCLUSIONS--Participation was influenced by attitudes towards audit in general and the advisory group in particular and by aspects of behaviour such as communication within the practice. Practical support and resources may help some practices undertake audit, but advisory groups must also deal with attitudes and unsatisfactory communication in practice teams. PMID:7613323

  7. Examining Factors Influencing the Behavioral Intention to Adopt Broadband in Malaysia

    NASA Astrophysics Data System (ADS)

    Dwivedi, Yogesh K.; Selamat, Mohamad H.; Wahab, Muhammad S. Abd; Samsudin, Mohd A. Mat; Lal, Banita

    The aim of this study was to examine the factors affecting the adoption of broadband Internet in a developing country context by focusing upon Malaysia. The data relating to these factors was collected using a survey approach. The findings of this paper suggest that perceived usefulness, perceived ease of use, and social influence are significant factors for explaining the behavioral intention to adopt broadband Internet by Malaysian accountants. The paper proceeds to outline the research limitations, theoretical contributions, and implications for practice.

  8. Factors influencing parental readiness to let their child with cancer die.

    PubMed

    Kars, Marijke C; Grypdonck, Mieke H F; Beishuizen, Auke; Meijer-van den Bergh, Esther M M; van Delden, Johannes J M

    2010-07-01

    One in four cases of childhood cancer is incurable. In these cases death can usually be anticipated and therefore preceded by a phase of palliative care. For parents, preparing to let their child die is an extraordinarily painful process. Most struggle to preserve their child. This study identified, from a parental perspective, the main factors that influence the transition from preserving life to letting go. A multi-centre, qualitative research, study was undertaken during the end-of-life (EoL) phase, comprising single or repeated interviews with 44 parents of 23 children with incurable cancer. We discovered that uncertainty, fragmentation and anxiety underpin the preserving life perspective. A perspective of letting go could be supported by a variety of factors. These included: Certainty that the child cannot be cured, postponed grief, the perception of suffering, the ability to disentangle needs and the ability to parent meaningfully. Hope, creating a peaceful parent-child relationship, and the attitude of professionals, could support movements in either direction. Of these, certainty, and in most cases postponed grief, were pre-conditions for the transition towards letting go. Strategies such as not challenging the parents' suppression of grief, creating certainty about the child's condition and supporting parents in efforts to redefine their parental role, supported progress towards accepting a letting go perspective. Parents' internal struggle between a preserving frame of mind and one of letting go is influenced by a combination of factors. However, professionals can influence some of these factors in order to facilitate this transition. Copyright 2010 Wiley-Liss, Inc.

  9. A Novel siRNA-Based Approach to Study Mechanisms of Resistance/Action of a New Drug in Treatment of Breast Cancer. Addendum

    DTIC Science & Technology

    2006-08-01

    electroporation, were tested in the MCF-7 breast cancer cell line. The cell line was then treated with a lethal dose of ET-743 and cytarabine , however no...drugs with known mechanisms of resistance, methotrexate (MTX) and cytarabine , using a clonogenic assay and MCF-7 breast cancer cells. 3. To employ...Aim 2. To test the ability of the generated siRNA library by using two drugs with known mechanisms of resistance, methotrexate (MTX) and cytarabine

  10. Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study.

    PubMed

    Thomas, Xavier; Elhamri, Mohamed; Raffoux, Emmanuel; Renneville, Aline; Pautas, Cécile; de Botton, Stéphane; de Revel, Thierry; Reman, Oumedaly; Terré, Christine; Gardin, Claude; Chelghoum, Youcef; Boissel, Nicolas; Quesnel, Bruno; Hicheri, Yosr; Bourhis, Jean-Henri; Fenaux, Pierre; Preudhomme, Claude; Michallet, Mauricette; Castaigne, Sylvie; Dombret, Hervé

    2011-08-18

    To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association-9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1(+) or CEBPA(+) and FLT3-ITD(-) had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.

  11. [Bioavailability and factors influencing its rate].

    PubMed

    Vraníková, Barbora; Gajdziok, Jan

    Bioavailability can be defined as the rate and range of active ingredient absorption, when it becomes available in the systemic circulation or at the desired site of drug action, respectively. Drug bioavailability after oral administration is affected by anumber of different factors, including physicochemical properties of the drug, physiological aspects, the type of dosage form, food intake, biorhythms, and intra- and interindividual variability of the human population. This article is the first from the series dealing with the bioavailability and methods leading to its improvement. The aim of the present paper is to provide an overview of aspects influencing the rate of bioavailability after oral administration of the active ingredient. Subsequentarticles will provide detailed descriptions of methods used for dug bioavailability improvement, which are here only summarized.

  12. Influencing factors of alexithymia in Chinese medical students: a cross-sectional study.

    PubMed

    Zhu, Yaxin; Luo, Ting; Liu, Jie; Qu, Bo

    2017-04-04

    A much higher prevalence of alexithymia has been reported in medical students compared with the general population, and alexithymia is a risk factor that increases vulnerability to mental disorders. Our aim was to evaluate the level of alexithymia in Chinese medical students and to explore its influencing factors. A cross-sectional study of 1,950 medical students at Shenyang Medical College was conducted in May 2014 to evaluate alexithymia in medical students using the Chinese version of the 20-item Toronto Alexithymia Scale (TAS-20). The reliability of the questionnaire was assessed by Cronbach's α coefficient and mean inter-item correlations. Confirmatory factor analysis (CFA) was used to evaluate construct validity. The relationships between alexithymia and influencing factors were examined using Student's t-test, analysis of variance, and multiple linear regression analysis. Statistical analysis was performed using SPSS 21.0. Of the 1,950 medical students, 1,886 (96.7%) completed questionnaires. Overall, Cronbach's α coefficient of the TAS-20 questionnaire was 0.868. The results of CFA showed that the original three-factor structure produced an acceptable fit to the data. By univariate analysis, gender, grade (academic year of study), smoking behavior, alcohol use, physical activity, history of living with parents during childhood, and childhood trauma were influencing factors of TAS-20 scores (p < 0.05). Multiple linear regression analysis showed that gender, physical activity, grade, living with parents, and childhood trauma also had statistically significant association with total TAS-20 score (p < 0.05). Gender, physical activity, grade, history of living with parents during childhood, and childhood trauma were all factors determining the level of alexithymia. To prevent alexithymia, it will be advisable to promote adequate physical activity and pay greater attention to male medical students and those who are in the final year of training.

  13. Factors that positively influence breastfeeding duration to 6 months: a literature review.

    PubMed

    Meedya, Shahla; Fahy, Kathleen; Kable, Ashley

    2010-12-01

    What modifiable factors positively influence breastfeeding duration to 6 months postpartum? This question was posed in order to be able to develop a midwifery intervention aimed at prolonging breastfeeding. An online literature search was conducted in Medline, CINAHL, Maternity and Infant Care, and Cochrane Database of systematic reviews. The search strategy included the following keywords: breastfeeding, duration, initiation, cessation, factors, intervention, education, partner, intention, confidence, self-efficacy and support. Additional studies were located and extracted from online publications of New South Wales Department of Health, Australia. Bio-psycho-social factors that are positively associated with breastfeeding duration were identified. Modifiable factors that influence women's breastfeeding decisions are: breastfeeding intention, breastfeeding self-efficacy and social support. Existing midwifery breastfeeding promotion strategies often include social support but do not adequately address attempts to modify breastfeeding intention and self-efficacy. The modifiable factors that are positively associated with breastfeeding duration are the woman's breastfeeding intention, her breastfeeding self-efficacy and her social support. Intervention studies to date have focussed on modifying these factors individually with variable results. No interventional studies have been conducted with the aim of positively modifying all three factors simultaneously. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  14. Factors that Influence Women's Technical Skill Development in Outdoor Adventure

    ERIC Educational Resources Information Center

    Warren, Karen; Loeffler, TA

    2006-01-01

    This article provides a theoretical foundation for understanding women's technical skill development (TSD) in outdoor adventure. An examination of societal and biological factors influencing women's TSD focuses on gender role socialization, sense of competence, technical conditioning, sexism, spatial ability, and risk-taking. The article suggests…

  15. An Examination of Factors Influencing Postsecondary Career and Technical Educational Engagement of African American Males

    ERIC Educational Resources Information Center

    Cunningham, Natalie Jo

    2016-01-01

    The purpose of this study was to assess the relative influence of career, financial, personal, and legal factors on African American male engagement in postsecondary career and technical education and to determine whether the influence of these factors was moderated by the participants having graduated or not graduated high school and by their…

  16. Interpersonal Interaction in Online Learning: Experienced Online Instructors' Perceptions of Influencing Factors

    ERIC Educational Resources Information Center

    York, Cindy S.; Richardson, Jennifer C.

    2012-01-01

    A multitude of factors influence interpersonal interaction between students and instructors in an online course. This study examines perceptions of six experienced online instructors to determine factors they believe increase interaction among their students and between the students and instructor of online courses. The end result is an inventory…

  17. A Comparative Study of Digital Library Use: Factors, Perceived Influences, and Satisfaction

    ERIC Educational Resources Information Center

    Liu, Ziming; Luo, Lili

    2011-01-01

    This study explores the extent to which undergraduate and graduate students in China differ in their digital library use. Unlike the factors promoting digital library use, non-use factors, perceived influences, and degree of satisfaction are quite different between undergraduate and graduate students due to their differing emphases and…

  18. [Factors influencing activity of oral anticoagulants. Interactions with drugs and food].

    PubMed

    Sawicka-Powierza, Jolanta; Rogowska-Szadkowska, Dorota; Ołtarzewska, Alicja Małgorzata; Chlabicz, Sławomir

    2008-05-01

    Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease and prosthetic hart valves and in the primary and secondary prevention of venous thromboembolism. They are also used for the prevention of thromboembolic events in patients with acute myocardial infarction and with angina pectoris, in patients with biological hart valves and after some types of orthopaedics surgery. The International Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is out of the therapeutic range. The aim of this study was to present information about the factors influencing activity of oral anticoagulants and interactions between oral anticoagulants and drugs or food. The effect of oral anticoagulants is influenced by genetic and environmental factors such as: medicines, food, diseases and pre-existing conditions. A common mutation in the gene coding for the cytochrome P450 (CYP2C9), with one or more combinations of its polymorphisms, is responsible for the reduced warfarin requirements or for the resistance to warfarin. A mutation in the factor IX is responsible for the risk of bleeding during OAC therapy without excessive prolongation of the prothrombin time (PT). Drugs, herbs and multivitamin supplements can alter the absorption, pharmacokinetics or pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in combination with OAC seem to be the most dangerous because they are available without prescription and are used without medical consultation. Patients on OAC therapy are sensitive to changing dietary intake of vitamin K, which is supplied from phylloquinones in plants or from vitamin K-containing medicines. The effect of OAC can be influenced by other existing factors like: fever, diarrhoea, alcohol abuse or physical hyperactivity. Some malignancies

  19. ABCC4 Is a Determinant of Cytarabine‐Induced Cytotoxicity and Myelosuppression

    PubMed Central

    Drenberg, CD; Hu, S; Li, L; Buelow, DR; Orwick, SJ; Gibson, AA; Schuetz, JD; Sparreboom, A

    2016-01-01

    Resistance to cytarabine remains a major challenge in the treatment of acute myeloid leukemia (AML). Based on previous studies implicating ABCC4/MRP4 in the transport of nucleosides, we hypothesized that cytarabine is sensitive to ABCC4‐mediated efflux, thereby decreasing its cytotoxic response against AML blasts. The uptake of cytarabine and its monophosphate metabolite was found to be facilitated in ABCC4‐expressing vesicles and intracellular retention was significantly impaired by overexpression of human ABCC4 or mouse Abcc4 (P < 0.05). ABCC4 was expressed highly in AML primary blasts and cell lines, and cytotoxicity of cytarabine in cells was increased in the presence of the ABCC4 inhibitors MK571 or sorafenib, as well as after ABCC4 siRNA. In Abcc4‐null mice, cytarabine‐induced hematological toxicity was enhanced and ex vivo colony‐forming assays showed that Abcc4‐deficiency sensitized myeloid progenitors to cytarabine. Collectively, these studies demonstrate that ABCC4 plays a protective role against cytarabine‐mediated insults in leukemic and host myeloid cells. PMID:26842729

  20. Synergy of sequential administration of a deglycosylated ricin A chain-containing combined anti-CD19 and anti-CD22 immunotoxin (Combotox) and cytarabine in a murine model of advanced acute lymphoblastic leukemia

    PubMed Central

    Barta, Stefan K.; Zou, Yiyu; Schindler, John; Shenoy, Niraj; Bhagat, Tushar D.; Steidl, Ulrich; Verma, Amit

    2013-01-01

    The outcome for patients with refractory or relapsed acute lymphoblastic leukemia (ALL) treated with conventional therapy is poor. Immunoconjugates present a novel approach and have recently been shown to have efficacy in this setting. Combotox is a mixture of two ricin-conjugated monoclonal antibodies (RFB4 and HD37) directed against CD19 and CD22, respectively, and has shown activity in pediatric and adult ALL. We created a murine xenograft model of advanced ALL using the NALM/6 cell line to explore whether the combination of Combotox with the cytotoxic agent cytarabine (Ara-C) results in better outcomes. In our model the combination of both low- and high-dose Combotox and Ara-C resulted in significantly longer median survival. Sequential administration of Ara-C and Combotox, however, was shown to be superior to concurrent administration. These findings have led to a phase I clinical trial exploring this combination in adults with relapsed or refractory B-lineage ALL (ClinicalTrials.gov identifier NCT01408160). PMID:22448921