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Sample records for escalation safety study

  1. Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs.

    Science.gov (United States)

    Axiak, Sandra M; Selting, Kim A; Decedue, Charles J; Henry, Carolyn J; Tate, Deborah; Howell, Jahna; Bilof, K James; Kim, Dae Y

    2011-01-01

    Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m(2), and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m(2). Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m(2). Grade 1-2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m(2).

  2. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours.

    NARCIS (Netherlands)

    Herpen, C.M.L. van; Eskens, F.A.; Jonge, M. de; Desar, I.M.E.; Hooftman, L.; Bone, E.A.; Timmer-Bonte, J.N.H.; Verweij, J.

    2010-01-01

    BACKGROUND: This Phase Ib dose-escalating study investigated safety, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK) and clinical antitumour activity of tosedostat (CHR-2797), an orally bioavailable aminopeptidase inhibitor, in combination with paclitaxel. METHODS:

  3. Safety of Intracavernous Bone Marrow-Mononuclear Cells for Postradical Prostatectomy Erectile Dysfunction: An Open Dose-Escalation Pilot Study.

    Science.gov (United States)

    Yiou, René; Hamidou, Leila; Birebent, Brigitte; Bitari, Dalila; Lecorvoisier, Philippe; Contremoulins, Isabelle; Khodari, Muhieddine; Rodriguez, Anne-Marie; Augustin, Déborah; Roudot-Thoraval, Françoise; de la Taille, Alexandre; Rouard, Hélène

    2016-06-01

    Evidence from animal models replicating postradical prostatectomy erectile dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and vasculogenic pRP-ED refractory to maximal medical treatment were divided into four equal groups treated with escalating BM-MNC doses (2×10(7), 2×10(8), 1×10(9), 2×10(9)). Tolerance was the primary endpoint. Secondary endpoints were the effects on erectile function and penile vascularization at 6 mo, as assessed using the International Index of Erectile Function-15 and Erection Hardness Scale questionnaires, and color duplex Doppler ultrasound. We measured the peak systolic velocity in cavernous arteries and assessed endothelial function using the penile nitric oxide release test. No serious side effects occurred. At 6 mo versus baseline, significant improvements of intercourse satisfaction (6.8±3.6, 3.9±2.5, p=0.044) and erectile function (17.4±8.9, 7.3±4.5, p=0.006) domains of the International Index of Erectile Function-15 and Erection Hardness Scale (2.6±1.1, 1.3±0.8, p=0.008) were observed in the total population. Spontaneous erections showed significantly greater improvement with the higher doses. Clinical benefits were associated with improvement of peak systolic velocity and of % penile nitric oxide release test and sustained after 1 yr. Our results need to be confirmed by phase 2 clinical trials. We report a phase 1/2 pilot clinical trial investigating cell therapy with injection of bone marrow mononucleated cells to treat postradical prostatectomy erectile dysfunction. No serious side effects occurred. Improvements of erectile function and penile vascularization were noted. Further studies are required to confirm these preliminary results. Copyright © 2015

  4. Botulinum toxin type B (Myobloc) in subjects with hemifacial spasm: results from an open-label, dose-escalation safety study.

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    Trosch, Richard M; Adler, Charles H; Pappert, Eric J

    2007-07-15

    Evaluate the safety of botulinum toxin type B (BoNT-B) in subjects with hemifacial spasm (HFS). This open-label, sequential dose-escalation study evaluated BoNT-B in subjects with HFS. Eligible subjects were enrolled and received a single injection of one of four sequential BoNT-B doses (100, 200, 400, or 800 U). Following injection, subjects were evaluated in person at Weeks 2 and 8 and by phone at Weeks 1, 4, and 10 and every 2 weeks thereafter until benefit was lost. Safety was assessed by adverse events (AEs), vital signs and clinical laboratory evaluation. The severity of HFS was assessed using a patient social impairment visual analog scale (VAS), subject severity of contraction VAS, the HFS physician assessment, and subject HFS frequency and severity assessment. Nineteen predominately Caucasian (92%) and female (67%) subjects (aged 36-80 years) with HFS participated in this study. Subjects remained in the study an average of 88 days (range of 41-332 days) after receiving a single dose of BoNT-B. No deaths, serious AEs or AEs leading to trial discontinuation occurred during the study period. Two subjects in the 400 U dose group requested early withdrawal, whereas all other subjects completed the study. A reduction in HFS severity was observed in subjects treated with doses of 200 U or more. Improvements in subject HFS assessments tended to return to baseline values by 8 weeks following injection. BoNT-B was well-tolerated and reduced HFS severity in subjects who received injections of 200 to 800 U. Additional investigation is necessary to confirm the findings from this open-label study. 2007 Movement Disorder Society

  5. A phase I dose-escalation study to evaluate safety and tolerability of sorafenib combined with sirolimus in patients with advanced solid cancer.

    NARCIS (Netherlands)

    Desar, I.M.E.; Timmer-Bonte, J.N.H.; Burger, D.M.; Graaf, W.T.A. van der; Herpen, C.M.L. van

    2010-01-01

    BACKGROUND: The combination of sorafenib (vascular endothelial growth factor receptor 2 inhibitor) and sirolimus (mammalian target of rapamycin inhibitor) might work synergistically. METHODS: A phase I dose-escalation study with sorafenib twice a day (b.i.d.) and sirolimus once daily (q.d.) was

  6. Phase 1 dose-escalating study to evaluate the safety, pharmacokinetics, and pharmacodynamics of a recombinant factor Xa variant (FXa(I16L) ).

    Science.gov (United States)

    Parsons-Rich, D; Hua, F; Li, G; Kantaridis, C; Pittman, D D; Arkin, S

    2017-05-01

    Essentials FXa(I16L) is a recombinant zymogen-like variant of activated coagulation factor X (FXa). A phase 1 dose escalation clinical trial of FXa(I16L) was conducted in healthy adults. FXa(I16L) was safe and tolerated at doses up to 5 μg/kg; no dose-limiting toxicity was observed. Data support further development of FXa(I16L) for patients with acute hemorrhagic conditions. Background FXa(I16L) (PF-05230907) is a zymogen-like variant of activated factor X (FXa). It shows enhanced resistance to inactivation by endogenous inhibitors as compared with wild-type FXa, and restores hemostatic activity in non-clinical models of various bleeding conditions. Objectives To evaluate the safety, pharmacokinetics and pharmacodynamics of FXa(I16L) by performing a phase 1, first-in-human, dose-escalation clinical trial in healthy adult volunteers. Methods Participants were assigned to one of six ascending single-dose cohorts (0.1, 0.3, 1, 2, 3 or 5 μg kg(-1) ), each planned to comprise six volunteers treated with FXa(I16L) and two treated with placebo. Assessments included safety monitoring, pharmacokinetic and pharmacodynamic (PD) analyses, and immunogenicity testing. Results The trial enrolled 49 male volunteers. Administration of a single intravenous bolus dose of FXa(I16L) was safe and tolerated at all dose levels tested, with no dose-limiting toxicity or serious adverse events. FXa(I16L) plasma levels appeared to increase dose-proportionally, with a half-life of ~ 4 min. Treatment-related PD changes were observed for activated partial thromboplastin time, thrombin generation assay, thrombin-antithrombin complexes, prothrombin fragment 1 + 2, and D-dimer. One volunteer had a weak and transient non-neutralizing antidrug antibody response, which did not cross-react with native FX or native FXa. Conclusions FXa(I16L) was safe and tolerated, and showed a pharmacologic effect in healthy adults when administered at doses up to 5 μg kg(-1) . The safety profile, pharmacokinetics

  7. Emergency Department Escalation in Theory and Practice: A Mixed-Methods Study Using a Model of Organizational Resilience.

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    Back, Jonathan; Ross, Alastair J; Duncan, Myanna D; Jaye, Peter; Henderson, Katherine; Anderson, Janet E

    2017-11-01

    Escalation policies are used by emergency departments (EDs) when responding to an increase in demand (eg, a sudden inflow of patients) or a reduction in capacity (eg, a lack of beds to admit patients). The policies aim to maintain the ability to deliver patient care, without compromising safety, by modifying "normal" processes. The study objective is to examine escalation policies in theory and practice. This was a mixed-method study involving a conceptual analysis of National Health Service escalation policies (n=12) and associated escalation actions (n=92), as well as a detailed ethnographic study of escalation in situ during a 16-month period in a large UK ED (n=30 observations). The conceptual analysis of National Health Service escalation policies found that their use requires the ability to dynamically reconfigure resources (staff and equipment), change work flow, and relocate patients. In practice, it was discovered that when the ED is under pressure, these prerequisites cannot always be attained. Instead, escalation processes were adapted to manage pressures informally. This adaptive need ("work as done") was found to be incompletely specified in policies ("work as imagined"). Formal escalation actions and their implementation in practice differed and varied in their effectiveness. Monitoring how escalation works in practice is essential in understanding whether and how escalation policies help to manage workload. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  8. A dose-escalation safety and immunogenicity study of a new live attenuated human rotavirus vaccine (Rotavin-M1) in Vietnamese children.

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    Dang, Duc Anh; Nguyen, Van Trang; Vu, Dinh Thiem; Nguyen, Thi Hien Anh; Nguyen, Duc Mao; Yuhuan, Wang; Baoming, Jiang; Nguyen, Dang Hien; Le, Thi Luan

    2012-04-27

    We tested a candidate live, oral, rotavirus vaccine (Rotavin-M1™) derived from an attenuated G1P [8] strain (KH0118-2003) isolated from a child in Vietnam. The vaccine was tested first for safety in 29 healthy adults. When deemed safe, it was further tested for safety and immunogenicity in 160 infants (4 groups) aged 6-12 weeks in a dose and schedule ranging study. The vaccine was administered in low titer (10(6.0)FFU/dose) on a 2-dose schedule given 2 months apart (Group 2L) and on a 3-dose schedule given 1 month apart (Group 3L) and in high titer (10(6.3)FFU/dose) in 2 doses 2 months apart (Group 2H) and in 3 doses 1 month apart (Group 3H). For comparison, 40 children (group Rotarix™) were given 2 doses of the lyophilized Rotarix™ vaccine (10(6.5)CCID(50)/dose) 1 month apart. All infants were followed for 30 days after each dose for clinical adverse events including diarrhea, vomiting, fever, abdominal pain, irritability and intussusception. Immunogenicity was assessed by IgA seroconversion and viral shedding was monitored for 7 days after administration of each dose. Two doses of Rotavin-M1 (10(6.3)FFU/dose) were well tolerated in adults. Among infants (average 8 weeks of age at enrollment), administration of Rotavin-M1 was safe and did not lead to an increased rate of fever, diarrhea, vomiting or irritability compared to Rotarix™, indicating that the candidate vaccine virus had been fully attenuated by serial passages. No elevation of levels of serum transaminase, blood urea, or blood cell counts were observed. The highest rotavirus IgA seroconversion rate (73%, 95%CI (58-88%)) was achieved in group 2H (2 doses--10(6.3)FFU/dose, 2 months apart). The 2 dose schedules performed slightly better than the 3 dose schedules and the higher titer doses performed slightly better than the lower titer doses. These rates of seroconversion were similar to that of the Rotarix™ group (58%, 95%CI (42-73%)). However more infants who received Rotarix™ (65%) shed virus

  9. First-in-human, open-label dose-escalation and dose-expansion study of the safety, pharmacokinetics, and antitumor effects of an oral ALK inhibitor ASP3026 in patients with advanced solid tumors

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    Tianhong Li

    2016-03-01

    Full Text Available Abstract Background ASP3026 is a second-generation anaplastic lymphoma kinase (ALK inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors. This open-label, multicenter, first-in-human phase I study ( NCT01284192 assessed the safety, pharmacokinetic profile, and antitumor activity of ASP3026. Methods Advanced solid tumor patients received oral ASP3026 in 3 + 3 dose-escalation cohorts at doses of 25–800 mg once daily in 28-day cycles. The endpoints were to identify the maximum tolerated dose (MTD, the recommended phase II dose (RP2D, and the pharmacokinetic profile of ASP3026. A phase Ib expansion cohort enrolled patients with metastatic, crizotinib-resistant ALK-positive solid tumors at the RP2D, and response was evaluated by RECIST 1.1. Results The dose-escalation cohort enrolled 33 patients, including three crizotinib-resistant, ALK-positive patients, and the dose-expansion cohort enrolled another 13 crizotinib-resistant, ALK-positive non-small cell lung cancer (NSCLC patients. ASP3026 demonstrated both linear pharmacokinetics and dose-proportional exposure for area under the plasma concentration–time curve and maximum concentration observed with a median terminal half-life of 35 h, supporting the daily dosing. Grade 3 rash and elevated transaminase concentrations were dose-limiting toxicities observed at 800 mg; hence, 525 mg daily was the MTD and RP2D. The most common treatment-related adverse events were nausea (38 %, fatigue (35 %, and vomiting (35 %. Among the 16 patients with crizotinib-resistant ALK-positive tumors (15 NSCLC, 1 neuroblastoma, eight patients achieved partial response (overall response rate 50 %; 95 % confidence interval 25–75 % and seven patients (44 % achieved stable disease. Conclusions ASP3026 was well tolerated and had therapeutic activity in patients with crizotinib-resistant ALK-positive advanced tumors. Trial registration ClinTrials.gov: NCT01284192

  10. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study.

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    Doi, Toshihiko; Shitara, Kohei; Naito, Yoichi; Shimomura, Akihiko; Fujiwara, Yasuhiro; Yonemori, Kan; Shimizu, Chikako; Shimoi, Tatsunori; Kuboki, Yasutoshi; Matsubara, Nobuaki; Kitano, Atsuko; Jikoh, Takahiro; Lee, Caleb; Fujisaki, Yoshihiko; Ogitani, Yusuke; Yver, Antoine; Tamura, Kenji

    2017-11-01

    Antibody-drug conjugates have emerged as a powerful strategy in cancer therapy and combine the ability of monoclonal antibodies to specifically target tumour cells with the highly potent killing activity of drugs with payloads too toxic for systemic administration. Trastuzumab deruxtecan (also known as DS-8201) is an antibody-drug conjugate comprised of a humanised antibody against HER2, a novel enzyme-cleavable linker, and a topoisomerase I inhibitor payload. We assessed its safety and tolerability in patients with advanced breast and gastric or gastro-oesophageal tumours. This was an open-label, dose-escalation phase 1 trial done at two study sites in Japan. Eligible patients were at least 20 years old with breast or gastric or gastro-oesophageal carcinomas refractory to standard therapy regardless of HER2 status. Participants received initial intravenous doses of trastuzumab deruxtecan from 0·8 to 8·0 mg/kg and dose-limiting toxicities were assessed over a 21-day cycle; thereafter, dose reductions were implemented as needed and patients were treated once every 3 weeks until they had unacceptable toxic effects or their disease progressed. Primary endpoints included identification of safety and the maximum tolerated dose or recommended phase 2 dosing and were analysed in all participants who received at least one dose of study drug. The dose-escalation study is the first part of a two-part study with the second dose-expansion part ongoing and enrolling patients as of July 8, 2017, in Japan and the USA. This trial is registered at ClinicalTrials.gov, number NCT02564900. Between Aug 28, 2015, and Aug 26, 2016, 24 patients were enrolled and received trastuzumab deruxtecan (n=3 for each of 0·8, 1·6, 3·2, and 8·0 mg/kg doses; n=6 for each of 5·4 and 6·4 mg/kg). Up to the study cutoff date of Feb 1, 2017, no dose-limiting toxic effects, substantial cardiovascular toxic effects, or deaths occurred. One patient was removed from the activity analysis because they

  11. Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study.

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    van Zandwijk, Nico; Pavlakis, Nick; Kao, Steven C; Linton, Anthony; Boyer, Michael J; Clarke, Stephen; Huynh, Yennie; Chrzanowska, Agata; Fulham, Michael J; Bailey, Dale L; Cooper, Wendy A; Kritharides, Leonard; Ridley, Lloyd; Pattison, Scott T; MacDiarmid, Jennifer; Brahmbhatt, Himanshu; Reid, Glen

    2017-10-01

    TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma. In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function. Patients were given TargomiRs via 20 min intravenous infusion either once or twice a week (3 days apart) in a traditional 3 + 3 dose-escalation design in five dose cohorts. The dose-escalation steps planned were 5 × 10 9 , 7 × 10 9 , and 9 × 10 9 TargomiRs either once or twice weekly, but after analysis of data from the first eight patients, all subsequent patients started protocol treatment at 1 × 10 9 TargomiRs. The primary endpoints were to establish the maximum tolerated dose of TargomiRs as measured by dose-limiting toxicity, define the optimal frequency of administration, and objective response (defined as the percentage of assessable patients with a complete or partial response), duration of response (defined as time from the first evidence of response to disease progression in patients who achieved a response), time to response (ie, time from start of treatment to the first evidence of response) and overall survival (defined as time from treatment allocation to death from any cause). Analyses were based

  12. Safety of a dose-escalated pre-workout supplement in recreationally active females.

    Science.gov (United States)

    Vogel, Roxanne M; Joy, Jordan M; Falcone, Paul H; Mosman, Matt M; Kim, Michael P; Moon, Jordan R

    2015-01-01

    Pre-workout supplements (PWS) have increased in popularity among athletic populations for their purported ergogenic benefits. Most PWS contain a "proprietary blend" of several ingredients, such as caffeine, beta-alanine, and nitrate in undisclosed dosages. Currently, little research exists on the safety and potential side effects of chronic consumption of PWS, and even less so involving female populations. Therefore, the purpose of the present study was to examine the safety of consuming a dose-escalated PWS over a 28-day period among active adult females. 34 recreationally active, adult females (27.1 ± 5.4 years, 165.2 ± 5.7 cm, 68.2 ± 16.0 kg) participated in this study. Participants were randomly assigned to consume either 1 (G1) or 2 (G2) servings of a PWS daily or remain unsupplemented (CRL) for a period of 28 days. All were instructed to maintain their habitual dietary and exercise routines for the duration of the study. Fasting blood samples, as well as resting blood pressure and heart rate, were taken prior to and following the supplementation period. Samples were analyzed for hematological and clinical chemistry panels, including lipids. Significant (p < 0.05) group by time interactions were present for absolute monocytes (CRL -0.10 ± 0.10; G1 + 0.03 ± 0.13; G2 + 0.01 ± 0.12×10E3/uL), MCH (CRL -0.13 ± 0.46; G1 + 0.36 ± 0.52; G2 -0.19 ± 0.39 pg), creatinine (CRL 0.00 ± 0.05; G1 -0.06 ± 0.13; G2 -0.14 ± 0.08 mg/dL), eGFR (CRL -0.69 ± 5.97; G1 + 6.10 ± 15.89; G2 + 14.63 ± 7.11 mL/min/1.73), and total cholesterol (CRL -2.44 ± 13.63; G1 + 14.40 ± 27.32; G2 -10.38 ± 15.39 mg/dL). Each of these variables remained within the accepted physiological range. No other variables had significant interactions. The present study confirms the hypothesis that a PWS containing caffeine, beta-alanine, and nitrate will not cause abnormal changes in

  13. Studying the efficacy of escalated dose conformal radiation therapy in prostate carcinoma – Pakistan experience

    Directory of Open Access Journals (Sweden)

    Asad Zamir

    2017-11-01

    Conclusion: Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity.

  14. Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Brezinski

    Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

  15. Efficacy and safety of fosmidomycin-piperaquine as non-artemisinin-based combination therapy for uncomplicated falciparum malaria - A single-arm, age-de-escalation proof of concept study in Gabon.

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    Mombo-Ngoma, Ghyslain; Remppis, Jonathan; Sievers, Moritz; Zoleko Manego, Rella; Endamne, Lilian; Kabwende, Lumeka; Veletzky, Luzia; Nguyen, The Trong; Groger, Mirjam; Lötsch, Felix; Mischlinger, Johannes; Flohr, Lena; Kim, Johanna; Cattaneo, Chiara; Hutchinson, David; Duparc, Stephan; Joerg, Moehrle; Velavan, Thirumalaisamy P; Lell, Bertrand; Ramharter, Michael; Adegnika, Ayola Akim; Mordmüller, Benjamin; Kremsner, Peter G

    2017-12-26

    Fosmidomycin-piperaquine is being developed as non-artemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. The study was a phase 2 single arm open label proof of concept study of the efficacy, tolerability and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum mono-infection in Gabon. Adults and children of both sexes with initial parasite counts between 1,000 and 150,000/µL were eligible for oral treatment with fosmidomycin (twice daily doses of 30mg/kg), and piperaquine (once daily dose of 16mg/kg) for three days and followed-up for 63 days. The primary efficacy endpoint was the per protocol PCR-corrected Day 28 adequate clinical and parasitological response (ACPR). 100 patients were enrolled. The PCR-corrected Day 28 ACPR rate was 83/83 or 100% (95% CI: 96-100). Fourteen patients had asexual parasitaemia between Day 28 and Day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median: 36h; IQR: 6-60) and fever clearance time (median: 12h; IQR: 6-48). The electrocardiogram assessments showed two subjects with QT corrected from the formula of Bazett (QTcB) >500msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. This is the first report of the use of the combination fosmidomycin-piperaquine, a non-artemisinin-based combination therapy in clinical development. The combination appeared to have high efficacy, to be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval.

  16. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

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    Stamp, Lisa K; Chapman, Peter T; Barclay, Murray L; Horne, Anne; Frampton, Christopher; Tan, Paul; Drake, Jill; Dalbeth, Nicola

    2017-09-01

    To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was gout. Allopurinol dose escalation is well tolerated. ANZCTR12611000845932; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-small cell lung cancer.

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    Soria, Jean-Charles; Adjei, Alex A; Bahleda, Rastilav; Besse, Benjamin; Ferte, Charles; Planchard, David; Zhou, Jing; Ware, Joseph; Morrissey, Kari; Shankar, Geetha; Lin, Wei; Schutzman, Jennifer L; Dy, Grace K; Groen, Harry J M

    2017-11-01

    The phosphatidylinositol 3-kinase (PI3K) pathway is a potential therapeutic target in non-small cell lung cancer (NSCLC). This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC. A 3 + 3 dose-escalation study was performed using a starting daily dose of 60 mg pictilisib on days 1-14 of a 21-day cycle. Depending on bevacizumab eligibility and NSCLC histology, patients also received either paclitaxel + carboplatin or pemetrexed + cisplatin, ± bevacizumab every 3 weeks. The primary objectives of the study were to assess safety and tolerability and to identify dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and a recommended phase II dose (RP2D), for each combination. All 66 treated patients experienced at least one adverse event (AE). Grade ≥III AEs, serious AEs and deaths occurred in 57 (86.4%), 56 (84.8%) and 9 (13.6%) patients, respectively. Three patients reported DLTs across the four arms of the study. The MTD was not reached in any arm and the RP2D of pictilisib was determined to be 330 mg (capsules) or 340 mg (tablets) on a '14 days on, 7 days off' schedule. The best confirmed response was partial response in 29 (43.9%) patients and stable disease in 20 (30.9%) patients. Combining pictilisib with various standard-of-care first-line treatment regimens is feasible from a safety perspective in patients with NSCLC, and encouraging preliminary anti-tumour activity was observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Long-term efficacy of botulinum toxin A for treatment of blepharospasm, hemifacial spasm, and spastic entropion: a multicentre study using two drug-dose escalation indexes.

    Science.gov (United States)

    Cillino, S; Raimondi, G; Guépratte, N; Damiani, S; Cillino, M; Di Pace, F; Casuccio, A

    2010-04-01

    To investigate the long-term effectiveness and safety of botulinum neurotoxin A (BoNT-A) treatment in patients with blepharospasm (BEB), hemifacial spasm (HFS), and entropion (EN) and to use for the first time two modified indexes, 'botulin toxin escalation index-U' (BEI-U) and 'botulin toxin escalation index percentage' (BEI-%), in the dose-escalation evaluation. All patients in this multicentre study were followed for at least 10 years and main outcomes were clinical efficacy, duration of relief, BEI-U and BEI-%, and frequency of adverse events. BEB, HFS, and EN patients received a mean BoNT-A dose with a significant inter-group difference (P<0.0005, respectively). The mean (+/-SD) effect duration was statistically different (P=0.009) among three patient groups. Regarding the BoNT-A escalation indexes, the mean (+/-SD) values of BEI-U and BEI-% were statistically different (P=0.035 and 0.047, respectively) among the three groups. In BEB patients, the BEI-% was significantly increased in younger compared with older patients (P=0.008). The most frequent adverse events were upper lid ptosis, diplopia, ecchymosis, and localized bruising. This long-term multicentre study supports a high efficacy and good safety profile of BoNT-A for treatment of BEB, HFS, and EN. The BEI indexes indicate a significantly greater BoNT-A-dose escalation for BEB patients compared with HFS or EN patients and a significantly greater BEI-% in younger vsolder BEB patients. These results confirm a greater efficacy in the elderly and provide a framework for long-term studies with a more flexible and reliable evaluation of drug-dose escalation.

  19. A phase I, dose-escalation trial evaluating the safety and efficacy of emulsified isoflurane in healthy human volunteers.

    Science.gov (United States)

    Huang, Han; Li, Rui; Liu, Jin; Zhang, Wensheng; Liao, Tianzhi; Yi, Xiaoqian

    2014-03-01

    This first-in-human volunteer phase I clinical trial aimed to evaluate the safety, tolerability, and anesthesia efficacy of emulsified isoflurane (EI), an intravenously injectable formulation of isoflurane. Seventy-eight healthy volunteers were recruited in this open-label, single-bolus, dose-escalation, phase I trial and were allocated into 16 cohorts. Each volunteer received a single bolus injection of EI. The dose started with 0.3 mg/kg (for isoflurane) and was planned to end with 64.6 mg/kg. Postdose vital signs, physical examination, laboratory tests, chest radiograph, 12-lead electrocardiogram, and development of any adverse event were closely monitored as safety measurements. Effectiveness in producing sedation/anesthesia was assessed by Modified Observer's Assessment of Alertness/Sedation and Bispectral Index. The dose escalation ended as planned. The most common adverse events associated with EI were injection pain (77 of 78, 98.7%) and transient tachycardia (22 of 78, 25.6%). Only at high doses (≥38.3 mg/kg) did EI cause transient hypotension (5 of 78, 6.4%) or apnea (11 of 78, 14.1%), but all the affected volunteers recovered uneventfully. Fast onset of unconsciousness (typically 40 s after injection) was developed in all volunteers receiving doses of 22.6 mg/kg or greater. Waking-up time and depression in Modified Observer's Assessment of Alertness/Sedation correlated well with EI dose. None of the postdose tests revealed any abnormal result. EI is safe for intravenous injection in human volunteers in the dose range of 0.3 to 64.6 mg/kg. At doses of 22.6 mg/kg or higher, EI produced rapid onset of unconsciousness in all volunteers followed by fast, predictable, and complete recovery.

  20. Lateral and escalation therapy in relapsing-remitting multiple sclerosis: a comparative study.

    Science.gov (United States)

    D'Amico, Emanuele; Leone, Carmela; Zanghì, Aurora; Fermo, Salvatore Lo; Patti, Francesco

    2016-09-01

    Performing a therapeutic switch in MS is still a matter of debate. Objective of our study is to compare switching to another first-line therapy with switching to a second-line therapy in persons with relapsing-remitting multiple sclerosis (pwRRMS). A retrospective analysis of data prospectively collected was performed. PwRRMS experiencing on-treatment disease activity were included. No clinical relapse, no sustained disability progression by the Expanded Disability Status Scale (EDSS), and no radiological activity (new T2 and/or gadolinium-enhanced brain lesions) were used as indicators of no disease activity (NEDA 3). Time to reach the first relapse after switch and time to reach an EDSS of 4.0 were also evaluated. Ninety-one pwRRMS were enrolled. Forty-eight (52.7 %) were on lateral switch, and 43 (47.3 %) on escalation switch. At baseline, the two groups differed for T2 and T1 brain lesions number (higher in the escalation group, p < 0.005). The proportion of pwRRMS who were NEDA 3 after 24 months from the switch was similar in the two groups (20.8 % in lateral group and 18.6 % in escalation group). No difference in timing to reach the first relapse after switch and an EDSS of 4.0 were found. Therefore, in selected pwRRMS, lateral and escalation strategies showed similar efficacy in delaying MS progression.

  1. Efficacy and safety of rapid escalation of cabergoline in comparison to conventional regimen for macroprolactinoma: A prospective, randomized trial

    Directory of Open Access Journals (Sweden)

    Ashu Rastogi

    2012-01-01

    Full Text Available Introduction: Cabergoline (CAB is conventionally started at a dose of 0.25-0.5 mg once a week with dose escalation at 1to 3months intervals. Previously, we and others have shown that rapid escalation and high doses of CAB can lead to normalization of serum PRL as early as 8.2 weeks in 93% of the patients. We hypothesize that rapid escalation of CAB doses, may help in both the earlier normalization of PRL and also significant shrinkage of tumor mass. Study Design: Randomized, prospective, interventional trial. Subjects and Methods: Forty two patients (male or female with macroprolactinoma were randomized to conventional (group A or rapid escalation (group B of CAB dosing. In group B, CAB was started at a dose of 0.5 mg twice a week followed by a weekly hike of 1 mg/week, based on serum PRL and then monthly. The end point of the present study was a composite of normoprolactinemia and tumor shrinkage ≥50% from baseline. PRL and visual field analysis (weekly, other hormonal work up periodically and magnetic resonance imaging (sella was performed monthly. Results: A total of 19 patients in each group completed a minimum follow-up of 6 months. There was a reduction of 72.7 ± 26.2% in group A and 84.1 ± 15.0 in group B (P = 0.24 within a week of CAB therapy. The duration of CAB treatment to normalize PRL was 10.2 ± 9.2 week(2-36 in group A and 7.2 ± 6.2 weeks(1-24 in group B (P = 0.28. There was no difference in the tumor shrinkage in either of the groups (92.3% [46.7-100%] in group A and 90.5% [66.6-100%] reduction in group B. The composite end point was achieved in 14 patients in group A (73.6% and 16 patients in group B (84.2% (P = 0.69. The composite end point was achieved in 13.1 ± 9.5 weeks (group A versus 16.5 ± 14.1 weeks (group B (P = 0.61. Discussion: This is first head to head comparative trial showing that a rapid hike of CAB dose is not associated with earlier normalization of PRL or reduction in tumor volume as compared to

  2. SYSTEMS-2: A randomised phase II study of radiotherapy dose escalation for pain control in malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    M. Ashton

    2018-01-01

    Full Text Available SYSTEMS-2 is a randomised study of radiotherapy dose escalation for pain control in 112 patients with malignant pleural mesothelioma (MPM. Standard palliative (20 Gy/5# or dose escalated treatment (36 Gy/6# will be delivered using advanced radiotherapy techniques and pain responses will be compared at week 5. Data will guide optimal palliative radiotherapy in MPM.

  3. Student nurses' de-escalation of patient aggression: a pretest-posttest intervention study.

    Science.gov (United States)

    Nau, Johannes; Halfens, Ruud; Needham, Ian; Dassen, Theo

    2010-06-01

    Experts recommend staff training to prevent and manage aggressive situations involving patients or their relatives. However, in many countries this subject is not covered in pre-registration nursing education. In addition, the evidence regarding its impact on practical placements remains weak. This study examines the influence of an aggression management training programme for nursing students on their performance in de-escalating aggressive patients. Pretest-posttest within-and-between-groups design. A School of Nursing in Germany. Convenience sample out of six classes of nursing students at differing educational levels (10th to 28th month of nursing education, n=78, mean age=22). In a cross-sectional and longitudinal two groups before and after design nursing students encountered two scenarios (A or B) with simulation patients. After completing the training, each student was confronted with the unknown other scenario. De-escalation experts from three German-speaking countries evaluated 156 video scenes using the De-escalating Aggressive Behaviour Scale (DABS), not knowing whether the videos had been recorded before or after the training. Mean values and statistical significance tests were computed to compare the results. The performance levels of students who had been trained rose significantly from 2.74 to 3.65 as measured by the DABS on a 5-point Likert scale (Wilcoxon test pstudents managed scenario A significantly better than the untrained students (untrained 2.50, trained 3.70; Mann-Whitney-U-test pstudents' age or duration of previous nursing education. Aggression management training is able to improve nursing students' performance in de-escalating aggressive behaviour. A maturation-effect on the de-escalating performance due to general nursing education or age is unlikely. (c) 2009 Elsevier Ltd. All rights reserved.

  4. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Blanck, Oliver, E-mail: oliver.blanck@uksh.de [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Bode, Frank [Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Gebhard, Maximilian [Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Hunold, Peter [Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Brandt, Sebastian [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Bruder, Ralf [Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Grossherr, Martin [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Vonthein, Reinhard [Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Rades, Dirk [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Dunst, Juergen [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); University Copenhagen (Denmark)

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  5. Narration and Escalation. An Empirical Study of Conflict Narratives

    Directory of Open Access Journals (Sweden)

    Evelyn Gius

    2016-06-01

    Full Text Available This article describes the methodology and the outcomes of an empirical study of conflict narratives. The narratological analysis deployed narratological catego­ries in the structuralist tradition based on Genette and was conducted with the help of the text annotation tool CATMA. The analysis aimed at covering as many narratological phenomena as possible by establishing 14 fields of narrato­logical phenomena that were annotated in a corpus of 39 factual narratives about situations at the workplace with and without conflicts. The evaluation of approximately 28,000 annotations brought to light a series of interrelations be­tween narratological phenomena and the presence or absence of conflicts in the narratives. Additionally, this approach led to the identification of some over­sights of narrative theory by detecting hitherto unnoticed interrelations among narratological concepts.

  6. Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis.

    Science.gov (United States)

    Onal, Sumru; Kazokoglu, Haluk; Koc, Aylin; Akman, Mehmet; Bavbek, Tayfun; Direskeneli, Haner; Yavuz, Sule

    2011-03-01

    To investigate the long-term efficacy and safety of low-dose and dose-escalating therapy of interferon alfa-2a in the treatment of Behçet uveitis. This study included 37 patients with refractory Behçet panuveitis unresponsive to conventional immunosuppressive therapy. Induction interferon alfa-2a therapy was given as a daily dose of 3.0 million IU (MIU) subcutaneously for 14 days. Maintenance dose was achieved with 3.0 MIU 3 times per week given subcutaneously. The dosage was increased sequentially to 4.5, 6.0, and 9.0 MIU 3 times per week if uveitis relapses occurred. Total therapy duration was 24 months. Primary outcome measure was control of uveitis with quiescence during maintenance therapy. Ocular relapses per patient-year before and after initiation of interferon alfa-2a therapy and a corticosteroid-sparing effect were secondary outcomes. We also estimated the rate of remission after discontinuing interferon alfa-2a therapy. During maintenance therapy, interferon alfa-2a controlled uveitis in 35 patients (95%). In 15 patients (41%), a maintenance dosage of 3.0 MIU 3 times per week controlled uveitis without any relapse. The rate of uveitis relapses decreased from 3.52 per patient-year before to 0.75 per patient-year after initiating interferon alfa-2a therapy. Seventeen patients were receiving systemic corticosteroids at the time of initiation of interferon therapy. During the maintenance stage, 9 patients were able to discontinue and 8 to taper systemic corticosteroid therapy. Survival analysis estimated that the rate of remission after discontinuation of interferon alfa-2a therapy was 76% by 3 months. The rate of remission remained stable thereafter. A treatment protocol using a low-dose and dose-escalating therapy with interferon alfa-2a was able to control and achieve remission of uveitis in most patients with refractory ocular Behçet disease.

  7. A phase I, dose-escalation study of volasertib combined with nintedanib in advanced solid tumors.

    Science.gov (United States)

    de Braud, F; Cascinu, S; Spitaleri, G; Pilz, K; Clementi, L; Liu, D; Sikken, P; De Pas, T

    2015-11-01

    Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases. This study determined the maximum tolerated dose (MTD) and pharmacokinetics of volasertib combined with nintedanib, a potent and orally bioavailable triple angiokinase inhibitor, in patients with advanced solid tumors. This open-label, dose-escalation trial recruited patients with advanced metastatic solid tumors following failure of conventional treatment (NCT01022853; Study 1230.7). Volasertib was administered by intravenous infusion over 2 h, starting at 100 mg in the first dose cohort. Nintedanib was administered orally at a dose of 200 mg twice daily. The first treatment cycle comprised 28 days (days 1-7 and days 9-28: nintedanib; day 8: volasertib). From cycle 2 onwards, volasertib was administered on day 1 of a 21-day cycle and nintedanib was administered days 2-21. The primary objective was the MTD of volasertib in combination with nintedanib. Thirty patients were treated. The MTD of volasertib plus fixed-dose nintedanib was 300 mg once every 3 weeks, the same as the recommended single-agent dose of volasertib in solid tumors. Two of 12 assessable patients treated with the MTD experienced dose-limiting toxicities [grade 3 increased alanine aminotransferase (ALT); grade 3 ALT increase and grade 3 increased aspartate aminotransferase]. Disease control [stable disease (SD)/partial response (PR)/complete response (CR)] was achieved in 18 patients (60%): 1 CR (breast cancer), 1 PR (nonsmall-cell lung cancer), and 16 patients with SD. Volasertib showed that multiexponential pharmacokinetic behavior and co-administration of nintedanib had no significant effects on its exposure. Volasertib could be combined with fixed-dose nintedanib at the recommended single-agent dose. At this dose, the combination had a manageable safety profile without unexpected or overlapping adverse events, and showed antitumor activity. © The Author

  8. Efficacy and safety of mixed amphetamine salts extended release (adderall XR) in the management of oppositional defiant disorder with or without comorbid attention-deficit/hyperactivity disorder in school-aged children and adolescents: A 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study.

    Science.gov (United States)

    Spencer, Thomas J; Abikoff, Howard B; Connor, Daniel F; Biederman, Joseph; Pliszka, Steven R; Boellner, Samuel; Read, Stephanie C; Pratt, Raymond

    2006-03-01

    Oppositional defiant disorder (ODD)is associated with a high degree of impairment in social skills, family interaction, and academic functioning. Comorbid ODD is reportedly present in 40% to 70% of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). The goal of this study was to assess the efficacy and safety of mixed amphetamine salts extended release (MAS XR) for the treatment of ODD in children and adolescents aged 6 to 17 years. This was a 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study. Patients were randomized to receive active treatment with MAS XR 10, 20, 30, or 40 mg/d or placebo. The primary efficacy end point was the ODD subscale of the Swanson, Nolan, and Pelham-IV (SNAP-IV) parent rating. Primary safety measures included adverse events recorded at each visit and for 30 days after study drug discontinuation, and changes in vital signs, 12-lead electrocardiographic (ECG) findings, laboratory tests and physical examinations, and body weight. A post hoc efficacy reanalysis was completed based on the results for the per-protocol population. For this analysis, patients were divided into high and low baseline severity categories according to the dichotomized baseline ODD parent or teacher score or dichotomized baseline ADHD parent or teacher score (high defined as scores at the median or greater and low defined as scores less than the median). A total of 308 children and adolescents (age range, 6-17 years; 213 males, 95 females) were randomized to receive active treatment with MAS XR 10 mg/d (n = 60) 20 mg/d (n = 58), 30 mg/d (n = 69), or 40 mg/d (n = 61) or placebo (n = 60). Of the 308 study patients, 244 (79.2%) had comorbid ADHD. A significant change from baseline in the ODD symptoms measured with the SNAP-IV parent rating subscale was found for the MAS XR 30-mg/d (-0.52; P < 0.001) and 40-mg/d (-0.56; P = 0.002) groups in the per-protocol analysis and for the MAS XR

  9. Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, Vedang, E-mail: vmurthy@actrec.gov.in [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India); Masodkar, Renuka; Kalyani, Nikhil; Mahantshetty, Umesh [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India); Bakshi, Ganesh; Prakash, Gagan [Department of Surgical Oncology, Tata Memorial Centre, Parel, Mumbai (India); Joshi, Amit; Prabhash, Kumar [Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai (India); Ghonge, Sujata; Shrivastava, Shyamkishore [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India)

    2016-01-01

    Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder

  10. A phase I dose-escalation and bioequivalence study of a trastuzumab biosimilar in healthy male volunteers.

    Science.gov (United States)

    Wisman, Liselijn A B; De Cock, Eduard P M; Reijers, Joannes A A; Kamerling, Ingrid M C; Van Os, Sandra H G; de Kam, Marieke L; Burggraaf, Jacobus; Voortman, Gerrit

    2014-12-01

    Trastuzumab (Herceptin(®)) is a humanized monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2) and is used in the treatment of HER2-overexpressing breast and gastric cancer. FTMB is being developed as a biosimilar of trastuzumab. In this combined dose-escalation and bioequivalence study of parallel design, the pharmacokinetic profile of FTMB was compared with Herceptin(®). Healthy male volunteers received single doses of 0.5, 1.5, 3.0 or 6.0 mg/kg FTMB, or placebo, in consecutive dose-escalation cohorts to assess the safety profile. Thereafter, the 6 mg/kg cohort was expanded to establish bioequivalence between FTMB (Test) and Herceptin(®) (Reference) based on an acceptance interval of 80.0-125.0 %. In total, 118 subjects were enrolled in the study. The mean area under the concentration-time curve from time zero to infinity (AUC∞) was 1,609 µg·day/mL (Test) and 1,330 µg·day/mL (Reference). The log-transformed geometric mean Test/Reference (T/R) ratio for AUC∞ was 89.6 % (90 % confidence interval [CI] 85.1-94.4), demonstrating bioequivalence. For the secondary endpoint, the maximum concentration observed (Cmax), the geometric mean T/R ratio was 89.4 % (90 % CI 83.4-95.9). Non-linear, target-mediated pharmacokinetics were also observed. Adverse events other than the documented side effects of Herceptin(®) (fever, influenza-like illness, and fatigue) did not occur. No signs of cardiotoxicity were observed. This bioequivalence study with a trastuzumab biosimilar in healthy male volunteers demonstrated bioequivalence of FTMB with Herceptin(®). FTMB was well tolerated in doses up to 6 mg/kg. Non-linear target elimination was also observed in the pharmacokinetic profile of trastuzumab.

  11. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study

    OpenAIRE

    Cirak, S.; Arechavala-Gomeza, V.; Guglieri, M.; Feng, L.; Torelli, S.; Anthony, K.; Abbs, S.; Garralda, M. E.; Bourke, J.; Wells, D. J.; Dickson, G.; Wood, M. J. A.; Wilton, S. D.; Straub, V.; Kole, R.

    2011-01-01

    Background We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate Morph lino oligomer (PMO) in patients with Duchenne muscular dystrophy.Method We undertook an open-label, phase 2, dose-escalation study (0.5, 1.0, 2.0, 4.0, 10.0, and 20.0 mg/kg bodyweight) in ambulant patients with Duchenne muscular dystrophy aged 5-15 years with amenable deletions in DMD. Participants had a muscle biopsy before starting treatment...

  12. A phase I, dose-escalation study of TB-403, a monoclonal antibody directed against PlGF, in patients with advanced solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Nielsen, D L; Sørensen, M

    2012-01-01

    and the terminal half-life values ranged from 9 to 14 days. Six patients exhibited stable disease for at least 8 weeks. Two patients, (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated with 5 mg kg(-1) weekly, remained stable for 12 months. CONCLUSION: TB-403 treatment in this patient......BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel antiangiogenesis agent directed against placental growth factor. The safety, pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase I, dose-escalation study in patients with advanced solid...

  13. Optimizing cancer radiotheraphy with 2-deoxy-D-glucose. Dose escalation studies in patients with glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Singh, D.; Gupta, J.P. [Dharmshila Cancer Hospital, New Delhi (India); Banerji, A.K. [Vidyasagar Inst. of Mental Health and Neurosciences, New Delhi (India); Dwarakanath, B.S.; Tripathi, R.P.; Mathew, T.L.; Ravindranath, T. [Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Jain, V. [Wright State University, Dayton, OH (United States). Kettering Medical Center

    2005-08-01

    Background and purpose: Higher rates of glucose utilization and glycolysis generally correlate with poor prognosis in several types of malignant tumors. Own earlier studies on model systems demonstrated that the nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) could enhance the efficacy of radiotherapy in a dose-dependent manner by selectively sensitizing cancer cells while protecting normal cells. Phase I/II clinical trials indicated that the combination of 2-DG, at an oral dose of 200 mg/kg body weight (BW), with large fractions of {gamma}-radiation was well tolerated in cerebral glioma patients. Since higher 2-DG doses are expected to improve the therapeutic gain, present studies were undertaken to examine the tolerance and safety of escalating 2-DG dose during combined treatment (2-DG + radiotherapy) in glioblastoma multiforme patients. Patients and methods: Untreated patients with histologically proven glioblastoma multiforme (WHO criteria) were included in the study. Seven weekly fractions of {sup 60}C {gamma}-rays (5 Gy/fraction) were delivered to the tumor volume (presurgical CT/MRI evaluation) plus 3 cm margin. Escalating 2-DG doses (200-250-300 mg/kg BW) were administered orally 30 min before irradiation after overnight fasting. Acute toxicity and tolerance were studied by monitoring the vital parameters and side effects. Late radiation damage and treatment responses were studied radiologically and clinically in surviving patients. Results: Transient side effects similar to hypoglycemia were observed in most of the patients. Tolerance and patient compliance to the combined treatment were very good up to a 2-DG dose of 250 mg/kg BW. However, at the higher dose of 300 mg/kg BW, two out of six patients were very restless and could not complete treatment, though significant changes in the vital parameters were not observed even at this dose. No significant damage to the normal brain tissue was observed during follow-up in seven out of ten patients who

  14. Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials.

    Science.gov (United States)

    Norrby, Maria; Vesikari, Timo; Lindqvist, Lars; Maeurer, Markus; Ahmed, Raija; Mahdavifar, Shahnaz; Bennett, Sean; McClain, J Bruce; Shepherd, Barbara M; Li, Daner; Hokey, David A; Kromann, Ingrid; Hoff, Søren T; Andersen, Peter; de Visser, Adriëtte W; Joosten, Simone A; Ottenhoff, Tom H M; Andersson, Jan; Brighenti, Susanna

    2017-03-14

    Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant. BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4+ T cell responses. H4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4+ T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4+ T cell expansion, IFN-γ production and multifunctional CD4+ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose. The novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4+ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31. ClinicalTrials.gov, NCT02066428 and NCT02074956. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. A phase I dose-escalation study of Tivantinib (ARQ 197) in adult patients with metastatic solid tumors.

    Science.gov (United States)

    Rosen, Lee S; Senzer, Neil; Mekhail, Tarek; Ganapathi, Ram; Chai, Feng; Savage, Ronald E; Waghorne, Carol; Abbadessa, Giovanni; Schwartz, Brian; Dreicer, Robert

    2011-12-15

    Tivantinib, an oral, non-ATP competitive, selective c-MET inhibitor, exhibited antitumor activity in preclinical models. This open-label, phase I, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of tivantinib in patients with advanced or metastatic solid tumors refractory to standard therapy. Thirteen dose levels of tivantinib ranging from 10 to 360 mg twice a day were administered to patient cohorts in 21-day cycles (14 days on/7 days off); three active pharmaceutical ingredient forms of tivantinib (amorphous, crystalline A, and crystalline B) were also investigated. Treatment was continued until the occurrence of unacceptable toxicity, tumor progression, patient withdrawal, or death. A total of 79 patients with advanced solid tumors were enrolled. A maximum tolerated dose was not determined. Tivantinib was well tolerated, with mild to moderate toxicities. Two patients discontinued the study drug due to treatment-emergent adverse events. Dose-limiting grade of 3 or more toxicities including leukopenia, neutropenia, thrombocytopenia, vomiting, and dehydration, were observed in 2 patients treated with tivantinib 360 mg twice a day. The rate of absorption of tivantinib peaked approximately 2 to 4 hours after initial dosing, followed by a linear decrease in plasma concentrations. Increases in tivantinib exposure were not dose proportional. There was significant interpatient pharmacokinetic variability; however the clinical safety of tivantinib seemed unaffected. Three patients (3.8%) achieved a partial response and 40 patients (50.6%) maintained stable disease for a median of 19.9 weeks. Tivantinib 360 mg twice a day was well tolerated in patients with refractory advanced solid tumors. The results of this trial warrant further clinical investigation. Clin Cancer Res; 17(24); 7754-64. ©2011 AACR. ©2011 AACR.

  16. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study.

    Science.gov (United States)

    Kaplovitch, Eric; Gomes, Tara; Camacho, Ximena; Dhalla, Irfan A; Mamdani, Muhammad M; Juurlink, David N

    2015-01-01

    The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.

  17. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Dienstmann, Rodrigo; Lassen, Ulrik; Cebon, Jonathan

    2016-01-01

    (18 %), fatigue (16 %) and nausea (13 %), mainly grade 1. Three patients (7 %) developed cutaneous squamous cell carcinoma. Photosensitivity, arthralgia and increased liver enzyme levels were each observed in only one patient each. Of 44 evaluable patients, 14 (32 %) had a partial response (melanoma......BACKGROUND: BRAF mutations are a validated target for cancer therapy. A second-generation BRAF inhibitor with an improved preclinical safety profile (RG7256) was evaluated in a first-in-man study in order to determine the safety, efficacy, pharmacokinetics and pharmacodynamics in patients with BRAF...... V600-mutated advanced solid tumors. PATIENTS AND METHODS: Patients received RG7256 orally over 8 dose levels from 200 mg once a day (QD) to 2400 mg twice a day (BID) (50-, 100- and 150-mg tablets) using a classic 3 + 3 dose escalation design. RESULTS: In total, 45 patients were enrolled; most (87...

  18. Caffeine in Parkinson's disease: a pilot open-label, dose-escalation study.

    Science.gov (United States)

    Altman, Robert D; Lang, Anthony E; Postuma, Ronald B

    2011-11-01

    Epidemiologic studies consistently find an inverse association between caffeine use and PD. Numerous explanations exist, but are difficult to evaluate as caffeine's symptomatic effect and tolerability in PD are unknown. We designed an open-label, 6-week dose-escalation study of caffeine to establish dose tolerability and evaluate potential motor/nonmotor benefits. Caffeine was started at 200 mg daily and was increased to a maximum of 1,000 mg. Of 25 subjects, 20 tolerated 200 mg, 17 tolerated 400 mg, 7 tolerated 800 mg, and 3 tolerated 1,000 mg. The most common adverse events were gastrointestinal discomfort, anxiety, and worsening/emerging tremor. At 400 mg daily, we found potential improvements in motor manifestations and somnolence (UPDRS III: -4.5 ± 4.6, P = 0.003; Epworth: -2.0 ± 3.0, P = 0.015). Maximum dose tolerability for caffeine in PD appears to be 100 to 200 mg BID. We found pilot preliminary evidence that caffeine may improve some motor and nonmotor aspects of PD, which must be confirmed in longer term, placebo-controlled, clinical trials. Copyright © 2011 Movement Disorder Society.

  19. Preliminary feasibility studies in times of rapid cost escalation. [Oil shale and tar sand industries

    Energy Technology Data Exchange (ETDEWEB)

    Oliver, E.D.; Moll, A.J.

    1976-01-01

    Not the least of the problems delaying the development and commercialization of synthetic fuel processes has been the extraordinary escalation of cost estimates by factors of up to ten in the past eight years. This study identifies and analyzes some of the most important contributing factors that have converged in the last few years. These factors include overoptimism and ill-defined project scope in the early stages, tightening environmental controls, difficulties in obtaining raw materials and fuels, general inflationary trends, ''hyperinflation'' of the costs of critical equipment, local labor shortages, and increased times required for procurement and construction. Cost increases have been particularly dramatic for ''offsites,'' liberally defined as nonprocess related parts of projects. Case histories of oil shale and tar sand developments are analyzed. Learning curves of costs during development and commercial use are studied. The analysis suggests that the worst of the extraordinary increases (above general inflationary trends) are probably over. Criteria to judge the state of development of processes are given, and some procedures to avoid future pitfalls are suggested.

  20. Tomotherapy PET-guided dose escalation. A dosimetric feasibility study for patients with malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Maggio, Angelo; Cutaia, Claudia; Di Dia, Amalia; Bresciani, Sara; Miranti, Anna; Poli, Matteo; Stasi, Michele [Candiolo Cancer Institute - FPO, IRCCS, Medical Physics, Turin (Italy); Del Mastro, Elena; Garibaldi, Elisabetta; Gabriele, Pietro [Candiolo Cancer Institute - FPO, IRCCS, Radiotherapy Department, Turin (Italy)

    2016-02-15

    The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT). We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV{sub 1}) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV{sub 2}). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV{sub 1} and 56 Gy (2.24 Gy/fraction) to the PTV{sub 2}, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans. For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V{sub 20}, V{sub 30}, and V{sub 40} DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001). The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs. (orig.) [German] Ziel war es, zu untersuchen, ob mit der helikalen Tomotherapie (HT) eine

  1. Safety of dexamphetamine in acute ischemic stroke: a randomized, double-blind, controlled dose-escalation trial.

    Science.gov (United States)

    Martinsson, Louise; Wahlgren, Nils Gunnar

    2003-02-01

    Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia. Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke. Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo (P< or =0.01). There was no difference between dexamphetamine and placebo regarding adverse events, body temperature, or consciousness level. During treatment, there was a benefit of dexamphetamine in neurological and functional outcome (P<0.05), but differences were not maintained at follow-up. Overall, dexamphetamine was safe and well tolerated by patients with acute cerebral ischemia, but blood pressure and heart rate increased during treatment in comparison to placebo. These observations may be important in the future planning of amphetamine trials because changes in these variables have been observed to interfere with clinical outcome. The suggestions of improvement in outcome must be confirmed in further studies.

  2. Gemcitabine plus dose-escalated epirubicin in advanced breast cancer: results of a phase I study.

    Science.gov (United States)

    Lüftner, D; Flath, B; Akrivakis, C; Mergenthaler, H G; Ohnmacht, U; Arning, M; Possinger, K

    1998-01-01

    Gemcitabine has shown single-agent activity in metastatic breast cancer. Epirubicin is also widely used for the adjuvant and treatment of metastatic breast cancer. The toxicity profiles and modes of action are different which provides a good rationale for studying both drugs in combination. In a phase I study gemcitabine at a fixed dose of 1000 mg/m2 on days 1, 8, 15 of a 28 day cycle was combined with escalated weekly doses of epirubicin starting with an initial dose of 10 mg/m2. Patients had stage IV metastatic disease without previous chemotherapy except as adjuvant treatment. Nineteen patients were included in the study which defined the maximum tolerated dose (MTD) of epirubicin at 20 mg/m2. Myelosuppression was the dose limiting toxicity with leucopenia WHO grade 3 and 4 in 40.0% and 20.0%, neutropenia WHO grade 3 and 4 without neutropenic fever in 20.0% and 40.0% and thrombocytopenia WHO grade 4 in 20.0%. At the epirubicin 15 mg/m2 dose level, leucopenia (11.1% WHO grade 3) and neutropenia (12.5 and 37.5% WHO grade 3 and 4) were reported. Symptomatic toxicity was generally mild: nausea/vomiting in about 20% of patients (WHO grade 3 or 4) on both 15 and 20 mg/m2 epirubicin dose levels. Alopecia WHO grade 3 and 4 was seen in 2 patients at MTD. Four of 19 evaluable patients had a partial response. We conclude that the combination of gemcitabine and epirubicin is well tolerated and has promising activity. A phase II study is underway with gemcitabine 1000 mg/m2 and epirubicin 15 mg/m2 on days 1, 8 and 15 of a 28 day cycle.

  3. Results of the phase I dose-escalating study of motexafin gadolinium with standard radiotherapy in patients with glioblastoma multiforme.

    Science.gov (United States)

    Ford, Judith M; Seiferheld, Wendy; Alger, Jeffrey R; Wu, Genevieve; Endicott, Thyra J; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-11-01

    Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

  4. A Phase I dose-escalation study of afatinib combined with nintedanib in patients with advanced solid tumors.

    Science.gov (United States)

    Gordon, Michael S; Springett, Gregory M; Su, Yungpo Bernard; Ould-Kaci, Mahmoud; Wind, Sven; Zhao, Yihua; LoRusso, Patricia M

    2015-01-01

    To evaluate the safety and maximum tolerated dose (MTD) of afatinib combined with nintedanib. Patients received afatinib 10-20 mg daily plus nintedanib 150-200 mg twice daily (28-day cycle). Dose escalation followed a 3+3 design. Patients received afatinib/nintedanib: 10/150 mg (n = 11); 10/200 mg (n = 13; MTD); 20/200 mg (n = 4). Four patients had dose-limiting toxicities (all grade 3): increased alanine aminotransferase (afatinib/nintedanib: 10/150 mg), diarrhea (10/200 mg), dehydration (20/200 mg), diarrhea with elevated liver enzymes (20/200 mg). Frequent treatment-related adverse events were diarrhea, nausea, anorexia, fatigue and vomiting. In total, 14 patients (46.2%) had objective responses at the MTD. The MTD, afatinib 10 mg daily plus nintedanib 200 mg twice daily, had a manageable safety profile, but was considered subtherapeutic for Phase II evaluation.

  5. The Role of Inflation and Price Escalation Adjustments in Properly Estimating Program Costs: F-35 Case Study

    Science.gov (United States)

    2016-04-30

    of price indexes presents a substantial challenge in estimating the costs of new defense systems . The problem is twofold. First, the analyst must...qÜáêíÉÉåíÜ=^ååì~ä= ^Åèìáëáíáçå=oÉëÉ~êÅÜ= póãéçëáìã= qÜìêëÇ~ó=pÉëëáçåë= sçäìãÉ=ff= = The Role of Inflation and Price Escalation Adjustments in Properly...The Role of Inflation and Price Escalation Adjustments in Properly Estimating Program Costs: F-35 Case Study Stanley Horowitz, Assistant Division

  6. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Eric Kaplovitch

    Full Text Available The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown.We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8% escalated to high dose therapy and n = 59 (0.2% died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70 and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53. These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy.Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.

  7. Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Piroth, M.D.; Pinkawa, M.; Holy, R. [RWTH Aachen University Hospital (Germany). Dept. of Radiation Oncology; Forschungszentrum Juelich GmbH (DE). Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain] (and others)

    2012-04-15

    Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [{sup 18}F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET{sub (72 Gy)} and PTV-MR{sub (60 Gy)}. FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR{sub (60 Gy)}. No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies. (orig.)

  8. Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation. A planning study

    Energy Technology Data Exchange (ETDEWEB)

    Botticella, A.; Defraene, G. [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); Nackaerts, K. [KU Leuven - University of Leuven, University Hospitals Leuven, Department of Respiratory Medicine, Leuven (Belgium); Deroose, C. [KU Leuven - University of Leuven, University Hospitals Leuven, Nuclear Medicine, Leuven (Belgium); Coolen, J. [KU Leuven - University of Leuven, University Hospitals Leuven, Radiology Department, Leuven (Belgium); Nafteux, P. [University Hospitals Leuven, Department of Thoracic Surgery, Leuven (Belgium); Vanstraelen, B. [University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Joosten, S.; Michiels, L.A.W. [Fontys University of Applied Science, Institute Paramedical Studies, Medical Imaging and Radiotherapeutic Techniques, Eindhoven (Netherlands); Peeters, S. [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); University Hospitals Leuven, Department of Radiation Oncology, Leuven (Belgium); Ruysscher, D. de [KU Leuven - University of Leuven, Department of Oncology, Experimental Radiation Oncology, Leuven (Belgium); Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Department of Radiation Oncology (MAASTRO Clinic), Maastricht (Netherlands)

    2017-04-15

    After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a ''selective'' PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an ''elective'' PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a ''selective'' pleural irradiation plan (SPI plan) and an ''elective'' pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). In the SPI plans, the average median dose to the S-PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S-PTV to >58 Gy. In the EPI plans, the average median doses to the E-PTV and to the S-PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM. (orig.) [German] Beim malignen Pleuramesotheliom (MPM) ist nach lungenschonender Radiotherapie das lokale Scheitern an Stellen eines frueheren, sichtbaren Tumors die dominierende Form des Scheiterns. Unser Ziel ist es, zu untersuchen, ob die selektive

  9. A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors.

    Science.gov (United States)

    Pant, S; Saleh, M; Bendell, J; Infante, J R; Jones, S; Kurkjian, C D; Moore, K M; Kazakin, J; Abbadessa, G; Wang, Y; Chen, Y; Schwartz, B; Camacho, L H

    2014-07-01

    Tivantinib (ARQ 197) is an orally available, non-adenosine triphosphate competitive, selective c-MET inhibitor. The primary objective of this study was to evaluate the safety, tolerability and to establish the recommended phase II dose (RP2D) of tivantinib and gemcitabine combination. Patients with advanced or metastatic solid tumors were treated with escalating doses of tivantinib (120-360 mg capsules) in combination with gemcitabine (1000 mg/m(2) weekly for 3 of 4 weeks). Different schedules of administration were tested and modified based on emerging preclinical data. Tivantinib was given continuously, twice a day (b.i.d.) for 2, 3 or 4 weeks of a 28-day cycle or on a 5-day on, 2-day off schedule (the day before and day of gemcitabine administration). Twenty-nine patients were treated with gemcitabine and escalating doses of tivantinib: 120 mg b.i.d. (n = 4), 240 mg b.i.d. (n = 6) and 360 mg b.i.d. (n = 19). No dose-limiting toxicities were observed in escalation. The RP2D was 360 mg b.i.d. daily, and 45 additional patients were enrolled in the expansion cohort. Grade ≥3 treatment-related toxicities were observed in 54 of 74 (73%) patients with the most common being neutropenia (43%), anemia (30%), thrombocytopenia (28%) and fatigue (15%). There was one treatment-related death due to neutropenia. Administration of gemcitabine did not affect tivantinib concentration. Fifty-six patients were assessable for response. Eleven (20%) patients achieved a partial response and 26 (46%) had stable disease (SD), including 15 (27%) who achieved SD for over 4 months. Ten of 37 patients with clinical benefit had prior exposure to gemcitabine. The combination of tivantinib at its monotherapy dose and standard dose gemcitabine was safe and tolerable. Early signs of antitumor activity may warrant further development of this combination in nonsmall-cell lung cancer, ovarian, pancreatic and cholangiocarcinoma. NCT00874042. © The Author 2014. Published by Oxford University Press

  10. Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer.

    Science.gov (United States)

    Mukai, Hirofumi; Takahashi, Shunji; Nozawa, Masahiro; Onozawa, Yusuke; Miyazaki, Jun; Ohno, Keiji; Suzuki, Kazuhiro

    2014-04-01

    The purpose of the study is to analyze the pharmacokinetic (PK) profile of cabazitaxel and evaluate its safety and tolerability as a 1-h IV infusion every 3 weeks in Japanese patients with castration-resistant prostate cancer (CRPC). Seventeen patients were treated with cabazitaxel at doses of 20 and 25 mg/m(2) for PK analyses. Dose escalation was performed only in the absence of dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) was the highest dose at which less than 33 % of the patients developed DLT. Cabazitaxel exhibited a triphasic elimination profile with a long terminal half-life of 116 ± 29.0 or 113 ± 28.0 h after IV infusion of 20 or 25 mg/m(2) cabazitaxel, respectively. The major differences in the PK parameters of cabazitaxel and docetaxel were cabazitaxel's fairly high clearance rate, representing approximately half the hepatic flow, and its large volume of distribution at steady-state conditions. No DLT was observed during Cycle 1. Mild-to-moderate hematological adverse events (AEs), including neutropenia, and other AEs typically associated with taxanes were observed; all AEs were manageable. Cabazitaxel at 25 mg/m(2) every 3 weeks was selected as the MTD in Japanese patients. The PK parameters of cabazitaxel in Japanese CRPC patients were comparable with those previously determined in Caucasian subjects. The safety and tolerability of cabazitaxel were also comparable in both ethnic populations.

  11. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  12. A single-blind, dose escalation, phase I study of high-fluence light-emitting diode-red light (LED-RL) on human skin: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Ho, Derek; Kraeva, Ekaterina; Wun, Ted; Isseroff, R Rivkah; Jagdeo, Jared

    2016-08-02

    Skin fibrosis is involved in a variety of pathologic conditions ranging from scar formation secondary to surgery or trauma to immune-mediated processes. Skin fibrosis is a significant international health problem with an estimated incidence of greater than 100 million people affected per year worldwide with few effective treatment options available. Preliminary in vitro data generated by our research group suggests that red light can function as a stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical trials have been performed to determine the safety of high-fluence (dose) light-emitting diode-red light (LED-RL) phototherapy. The goal of this study is to evaluate the safety of LED-RL fluences from 160 J/cm(2) up to 640 J/cm(2) in healthy subjects. This is a single-blind, dose escalation, randomized controlled, phase I study to evaluate the safety of high-fluence LED-RL on human skin. The protocol for dose escalation requires subjects be enrolled sequentially in groups of five. Within each group, three subjects will be randomized to LED-RL phototherapy and two subjects randomized to mock therapy. Subjects in group 1 randomized to LED-RL phototherapy will receive the maximum recommended starting dose (160 J/cm(2)). LED-RL dose will be escalated in subsequent groups (320 J/cm(2), 480 J/cm(2) and 640 J/cm(2)). The maximally tolerated dose (MTD) is defined as the dose level below the dose producing unacceptable but reversible toxicity and is considered to be the upper limit of subject tolerance. After either a MTD has been established, or the study endpoint of 640 J/cm(2) has been achieved, an additional 27 LED-RL phototherapy subjects (for a total of 30) and 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled. Each subject will receive a total of nine procedures, three times per week for three consecutive weeks. This study may provide important safety information on the effects of high-fluence LED

  13. Effects of donepezil dose escalation in Parkinson's patients with dementia receiving long-term donepezil treatment: an exploratory study.

    Science.gov (United States)

    Ishikawa, Kei-Ichi; Motoi, Yumiko; Mizuno, Yoshikuni; Kubo, Shin-Ichiro; Hattori, Nobutaka

    2014-06-01

    The benefits of escalating the dose of donepezil in patients who are already receiving long-term treatment with it have not been well evaluated. Therefore, an exploratory study to assess the effects of donepezil dose escalation in patients with Parkinson's disease with dementia, and specifically on patients receiving long-term treatment with donepezil, was performed. Patients treated with 5-mg/day donepezil for at least 3 months and having a Mini-Mental State Examination (MMSE) score between 10 and 26 were included in this study. Donepezil dosage was then increased to 10 mg/day for 12 weeks. The outcome measures were a modified form of the Neuropsychiatric Inventory (NPI) with an extra domain for additional evaluation of fluctuation in cognitive functions (NPI-11) and the MMSE. Of the nine patients enrolled, two withdrew because of nausea and inability to be assessed on the predetermined date; this left seven participants (four men and three women) with a mean age of 74.6 ± 6.9 years, a mean period of Parkinson's disease of 11.7 ± 7.5 years, and median donepezil use of 7 months (range: 3-56 months). At baseline, the mean total NPI-11 and mean MMSE scores were 18.3 ± 5.6 points and 21.3 ± 5.3 points, respectively. At week 12, they improved by 8.3 points (P donepezil from 5 mg/day to 10 mg/day may be therapeutically useful for patients with Parkinson's disease with dementia who have taken donepezil 5 mg/day in the long term. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

  14. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination With Docetaxel

    National Research Council Canada - National Science Library

    Vallabhajosula, Shankar

    2006-01-01

    Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

  15. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

    National Research Council Canada - National Science Library

    Vallabhajosula, Shankar

    2007-01-01

    Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

  16. Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

    Science.gov (United States)

    Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

    2017-03-01

    Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

  17. Dose escalation of a curcuminoid formulation

    Directory of Open Access Journals (Sweden)

    Crowell James

    2006-03-01

    Full Text Available Abstract Background Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complex™, Sabinsa Corporation. Healthy volunteers were administered escalating doses from 500 to 12,000 mg. Results Seven of twenty-four subjects (30% experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. Conclusion The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.

  18. A phase I safety and immunogenicity dose escalation trial of plague vaccine, Flagellin/F1/V, in healthy adult volunteers (DMID 08-0066).

    Science.gov (United States)

    Frey, Sharon E; Lottenbach, Kathleen; Graham, Irene; Anderson, Edwin; Bajwa, Kanwaldeep; May, Ryan C; Mizel, Steven B; Graff, Aaron; Belshe, Robert B

    2017-12-04

    Intentional aerosolization of Yersinia pestis may result in pneumonic plague which is highly fatal if not treated early. We conducted a phase 1 randomized, double blind (within each group), placebo controlled, dose escalation trial to evaluate a plague vaccine, Flagellin/F1/V, in healthy adults aged 8 through 45years. Vaccine was administered intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10mcg. Subjects were observed for 4h after vaccination for cytokine release syndrome. Reactogenicity and adverse events (AE) were collected for 14 and 28days, respectively, after each vaccination. Serious AE were collected for the entire study. ELISA antibody and cytokines were measured at multiple time points. Subject's participation lasted 13months. Sixty healthy subjects were enrolled; 52% males, 100% non-Hispanic, 91.7% white and mean age 30.8years. No severe reactogenicity events occurred; most AE were mild. No serious AE related to vaccine occurred. A dose response effect was observed to F1, V and flagellin. The peak ELISA IgG antibody titers (95% CI) after two 10mcg doses of vaccine were 260.0 (102.6-659.0) and 983.6 (317.3-3048.8), respectively, against F1 and V antigens. The 6mcg dose group provided similar titers. Titers were low for the placebo, 1mcg and 3mcg recipients. A positive antibody dose response was observed to F1, V and flagellin. Vaccine antigen specific serum IgE was not detected. There were no significant rises in serum or cellular cytokine responses and no significant IgG increase to flagellin after the second dose. The Flagellin/F1/V vaccine exhibited a dose dependent increase in immunogenicity and was well tolerated at all doses. Antibody specific responses to F1, V and flagellin increased as dose increased. Given the results from this trial, testing higher doses of the vaccine may be merited. Copyright © 2017. Published by Elsevier Ltd.

  19. Escalation of Commitment in the Surgical ICU.

    Science.gov (United States)

    Braxton, Carla C; Robinson, Celia N; Awad, Samir S

    2017-04-01

    Escalation of commitment is a business term that describes the continued investment of resources into a project even after there is objective evidence of the project's impending failure. Escalation of commitment may be a contributor to high healthcare costs associated with critically ill patients as it has been shown that, despite almost certain futility, most ICU costs are incurred in the last week of life. Our objective was to determine if escalation of commitment occurs in healthcare settings, specifically in the surgical ICU. We hypothesize that factors previously identified in business and organizational psychology literature including self-justification, accountability, sunk costs, and cognitive dissonance result in escalation of commitment behavior in the surgical ICU setting resulting in increased utilization of resources and cost. A descriptive case study that illustrates common ICU narratives in which escalation of commitment can occur. In addition, we describe factors that are thought to contribute to escalation of commitment behaviors. Escalation of commitment behavior was observed with self-justification, accountability, and cognitive dissonance accounting for the majority of the behavior. Unlike in business decisions, sunk costs was not as evident. In addition, modulating factors such as personality, individual experience, culture, and gender were identified as contributors to escalation of commitment. Escalation of commitment occurs in the surgical ICU, resulting in significant expenditure of resources despite a predicted and often known poor outcome. Recognition of this phenomenon may lead to actions aimed at more rational decision making and may contribute to lowering healthcare costs. Investigation of objective measures that can help aid decision making in the surgical ICU is warranted.

  20. Dose-escalation study for the targeting of CD44v+cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

    Science.gov (United States)

    Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Imamura, Chiyo K; Ozeki, Takeshi; Ishii, Yuya; Tsuchihashi, Kenji; Takahashi, Shunji; Nakajima, Takako E; Hironaka, Shuichi; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Einaga, Yasuaki; Kuwata, Takeshi; Saya, Hideyuki; Ohtsu, Atsushi

    2017-03-01

    Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

  1. A dose-escalation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine for the therapy of patients with metastatic melanoma.

    Science.gov (United States)

    Eigentler, Thomas K; Weide, Benjamin; de Braud, Filippo; Spitaleri, Gianluca; Romanini, Antonella; Pflugfelder, Annette; González-Iglesias, Reinerio; Tasciotti, Annaelisa; Giovannoni, Leonardo; Schwager, Kathrin; Lovato, Valeria; Kaspar, Manuela; Trachsel, Eveline; Menssen, Hans D; Neri, Dario; Garbe, Claus

    2011-12-15

    L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma. The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m(2) of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2. The recommended dose of L19-IL2 in combination with dacarbazine was defined as 22.5 Mio IU. Toxicity was manageable and reversible, with no treatment-related deaths. Twenty-nine patients were evaluable for efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST). In a centralized radiology analysis, eight of 29 (28%) patients achieved a RECIST-confirmed objective response, including a complete response still ongoing 21 months after treatment beginning. The 12-month survival rate and median overall survival of the recommended dose-treated patients (n = 26) were 61.5% and 14.1 months, respectively. The repeated administration of L19-IL2 in combination with dacarbazine is safe and shows encouraging signs of clinical activity in patients with metastatic melanoma. This combination therapy is currently evaluated in a randomized phase II trial with patients with metastatic melanoma. ©2011 AACR.

  2. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Gustav J Ullenhag

    Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

  3. Chemoradiation of hepatic malignancies: prospective, phase 1 study of full-dose capecitabine with escalating doses of yttrium-90 radioembolization.

    Science.gov (United States)

    Hickey, Ryan; Mulcahy, Mary F; Lewandowski, Robert J; Gates, Vanessa L; Vouche, Michael; Habib, Ali; Kircher, Sheetal; Newman, Steven; Nimeiri, Halla; Benson, Al B; Salem, Riad

    2014-04-01

    Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ((90)Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of (90)Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver (90)Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after (90)Y infusion. If a DLT was not observed, the (90)Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of (90)Y with full-dose capecitabine. Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing (90)Y MTD were not met, indicating an MTD of >170 Gy. The MTD of (90)Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest (90)Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Chemoradiation of Hepatic Malignancies: Prospective, Phase 1 Study of Full-Dose Capecitabine With Escalating Doses of Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Hickey, Ryan [Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Mulcahy, Mary F. [Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois (United States); Lewandowski, Robert J.; Gates, Vanessa L.; Vouche, Michael; Habib, Ali [Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Kircher, Sheetal; Newman, Steven; Nimeiri, Halla; Benson, Al B. [Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois (United States); Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois (United States)

    2014-04-01

    Purpose: Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ({sup 90}Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of {sup 90}Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. Methods and Materials: Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver {sup 90}Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after {sup 90}Y infusion. If a DLT was not observed, the {sup 90}Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of {sup 90}Y with full-dose capecitabine. Results: Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing {sup 90}Y MTD were not met, indicating an MTD of >170 Gy. Conclusion: The MTD of {sup 90}Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest {sup 90}Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.

  5. A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients.

    Science.gov (United States)

    Carlier, Mieke; Roberts, Jason A; Stove, Veronique; Verstraete, Alain G; Lipman, Jeffrey; De Waele, Jan J

    2015-08-01

    De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study.

    Science.gov (United States)

    Cassier, Philippe A; Italiano, Antoine; Gomez-Roca, Carlos A; Le Tourneau, Christophe; Toulmonde, Maud; Cannarile, Michael A; Ries, Carola; Brillouet, Anne; Müller, Claudia; Jegg, Anna-Maria; Bröske, Ann-Marie; Dembowski, Markus; Bray-French, Katharine; Freilinger, Christine; Meneses-Lorente, Georgina; Baehner, Monika; Harding, Ross; Ratnayake, Jayantha; Abiraj, Keelara; Gass, Nathalie; Noh, Karen; Christen, Randolph D; Ukarma, Lidia; Bompas, Emmanuelle; Delord, Jean-Pierre; Blay, Jean-Yves; Rüttinger, Dominik

    2015-08-01

    Diffuse-type tenosynovial giant cell tumour (dt-GCT) of the soft tissue (alternatively known as pigmented villonodular synovitis), an orphan disease with unmet medical need, is characterised by an overexpression of colony-stimulating factor 1 (CSF1), and is usually caused by a chromosomal translocation involving CSF1. CSF1 receptor (CSF1R) activation leads to the recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage that constitute the tumor mass in dt-GCT. Emactuzumab (RG7155) is a novel monoclonal antibody that inhibits CSF1R activation. We have assessed the safety, tolerability and activity of emactuzumab in patients with Dt-GCT of the soft tissue. In this phase 1, first-in-human dose-escalation and dose-expansion study, eligible patients were aged 18 years or older with dt-GCT of the soft tissue with locally advanced disease or resectable tumours requiring extensive surgery, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease according to Response Evaluation Criteria In Solid Tumors version 1.1, and adequate end-organ function. Patients with GCT of the bone were not eligible. Patients received intravenous emactuzumab at 900 mg, 1350 mg, or 2000 mg every 2 weeks in the dose-escalation phase and at the optimal biological dose in a dose-expansion phase. The primary objective was to evaluate the safety and tolerability of emactuzumab, and to determine the maximum tolerated dose or optimal biological dose. All treated patients were included in the analyses. Expansion cohorts are currently ongoing. This study is registered with ClinicalTrials.gov, number NCT01494688. Between July 26, 2012, and Oct 21, 2013, 12 patients were enrolled in the dose-escalation phase. No dose-limiting toxicities were noted in the dose-escalation cohort; on the basis of pharmacokinetic, pharmacodynamic, and safety information, we chose a dose of 1000 mg every 2 week for the dose-expansion cohort, into which 17 patients were enrolled

  7. Escalate shamefully, de-escalate angrily or gratefully: the influence of discrete emotions on escalation of commitment.

    Science.gov (United States)

    Dang, Junhua; Xiao, Shanshan; Liljedahl, Sophie

    2014-08-01

    Decision makers often tend to escalate their commitment when faced with a dilemma of whether to continue a losing course of action. Researchers recently began to investigate the influence of discrete emotions on this decision tendency. However, this work has mainly focused on negative emotions and rarely considered positive emotions, to say nothing of comparing the effects of both of them simultaneously. The current study addresses this need by presenting the results of three experiments that examined the effects of four emotions of both positive and negative valences in escalation situations. Experiment 1 investigated the relationships of three trait emotions (hope, shame, and anger) and escalation of commitment. Experiments 2 and 3 examined the effects of three induced emotions (anger, shame, and gratitude) on escalation of commitment in a student sample and an employee sample, respectively. The results revealed that the effects of discrete emotions in escalation situations are mainly due to their associated differences on the appraisal dimension of responsibility that is related to escalation situations rather than their valence. The theoretical and practical implications are discussed. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  8. A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma

    DEFF Research Database (Denmark)

    Hansson, Markus; Gimsing, Peter; Badros, Ashraf

    2015-01-01

    PURPOSE: This multicenter, first-in-human study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of BI-505, a human anti-ICAM-1 monoclonal antibody, in advanced relapsed/refractory multiple myeloma patients. EXPERIMENTAL DESIGN: BI-505 was given intravenously, every 2 weeks,...

  9. Hypofractionated Dose Escalated 3D Conformal Radiotherapy for Prostate Cancer: Outcomes from a Mono-Institutional Phase II Study.

    Science.gov (United States)

    Tramacere, Francesco; Arcangeli, Stefano; Pignatelli, Antonietta; Castagna, Roberta; Portaluri, Maurizio

    2015-05-01

    (bNED) was 83% for all patients. Our study confirms that 3D conformal radiotherapy (3DCRT) remains a safe and effective method to deliver a dose-escalated hypofractionated regimen for PCa patients in all risk classes with acceptable toxicity rates and optimal biochemical control. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Phase-I dose escalation and sequencing study of docetaxel and continuous infusion topotecan in patients with advanced malignancies.

    Science.gov (United States)

    Posey, James A; Wang, Hui; Hamilton, Joelle; Delgrosso, Alma; Zhang, Ruiwen; Freda, Timothy; Zamboni, William C

    2005-08-01

    Anti-tumor activity can often be enhanced with combination therapy in managing patients with metastatic cancer. However, dose sequence and schedule of delivery can alter the pharmacokinetics, toxicity, and anti-tumor response. Therefore, attention to drug-drug interactions which may be sequence or schedule-dependent are necessary. Docetaxel and topotecan are non-cross-resistance cytotoxic agents with activity in a variety of malignancies. The goal of this study was to determine the maximum tolerated dose of docetaxel and continuous infusion topotecan using two sequences of administration. Patients were randomized to schedule A or B and enrolled in four escalating-dose cohorts. On schedule A, docetaxel was administered over 1 h and followed by topotecan administered over 72 h. On schedule B, topotecan was given as a 72 h continuous infusion followed by a 1 h infusion of docetaxel. While the doses for the docetaxel and topotecan were the same for schedule A and schedule B, the toxicities, and thus the determination of maximum tolerated dose (MTD), were assessed independently. The plasma pharmacokinetic disposition of topotecan and docetaxel were evaluated during the first cycle of each sequence to assess drug interactions. Thirty patients, 20 males and 10 females were evaluable for toxicity and response. Four patients were chemonaive. Mean number cycles given were 3. Grade 3/4 thrombocytopenia and neutropenia were comparable on both schedules, as was the dose-limiting toxicity (DLT) for both schedules. There were no apparent differences in absolute neutrophil count or platelet nadirs between schedules A and B for three of the four cohorts. The principal non-hematologic toxicity was nausea and vomiting. The time of overlap of topotecan lactone or total concentrations and docetaxel concentrations were greater on schedule A as compared with schedule B and was associated with reduced clearance of docetaxel on schedule A as compared to schedule B. However, the mean

  11. Dose Escalation of Tamoxifen in Patients with Low Endoxifen Level: Evidence for Therapeutic Drug Monitoring-The TADE Study.

    Science.gov (United States)

    Fox, Peter; Balleine, Rosemary L; Lee, Clara; Gao, Bo; Balakrishnar, Bavanthi; Menzies, Alexander M; Yeap, Shang Heng; Ali, Sayed Sahanawaz; Gebski, Val; Provan, Pamela; Coulter, Sally; Liddle, Christopher; Hui, Rina; Kefford, Richard; Lynch, Jodi; Wong, Mark; Wilcken, Nicholas; Gurney, Howard

    2016-07-01

    Endoxifen is the major mediator of tamoxifen effect and endoxifen levels <15 nmol/L may be associated with increased risk of breast cancer recurrence. We increased tamoxifen dose in breast cancer patients with low endoxifen levels and assessed the influence of various parameters on reaching 15 nmol/L and 30 nmol/L endoxifen levels. Tamoxifen dose was increased in those with endoxifen levels below 30 nmol/L. Toxicity, including hot flash score, was measured. CYP2D6 metabolizer status was classified as ultra-rapid (UM), extensive (EM), intermediate (IM), or poor (PM) based genotype of somatic DNA. Dosage was escalated in 68 of 122 participants. On 20 mg tamoxifen, 24% had endoxifen levels below 15 nmol/L and this reduced to 6% following dose escalation. In over 50% of cases, there was no identified cause for low endoxifen. Low baseline endoxifen level, and not CYP2D6 metabolizer status, independently predicted reaching threshold targets for both the 15 nmol/L and 30 nmol/L targets (P = 0.04 and 0.003 respectively). The 15 nmol/L target was reached in all UM/EM and IM patients, 63% of PM patients, and 58% of those with baseline endoxifen of <10 nmol/L. There was no correlation between hot flash score and genotype or any tamoxifen metabolite level including endoxifen (R = 0.07). Low endoxifen on standard dose tamoxifen was the only independent predictor of failure to achieve potentially therapeutic levels. Trials examining tamoxifen dose escalation and breast cancer outcome should be guided by endoxifen levels alone, without reference to CYP2D6 genotype or presence of hot flashes. Clin Cancer Res; 22(13); 3164-71. ©2016 AACRSee related commentary by Hertz and Rae, p. 3121. ©2016 American Association for Cancer Research.

  12. Impact of de-escalation of beta-lactam antibiotics on the emergence of antibiotic resistance in ICU patients: a retrospective observational study.

    Science.gov (United States)

    De Bus, Liesbet; Denys, Wouter; Catteeuw, Julie; Gadeyne, Bram; Vermeulen, Karel; Boelens, Jerina; Claeys, Geert; De Waele, Jan J; Decruyenaere, Johan; Depuydt, Pieter O

    2016-06-01

    Antibiotic de-escalation is promoted to limit prolonged exposure to broad-spectrum antibiotics, but proof that it prevents the emergence of resistance is lacking. We evaluated determinants of antibiotic de-escalation in an attempt to assess whether the latter is associated with a lower emergence of antimicrobial resistance. Antibiotic treatments, starting with empirical beta-lactam prescriptions, were prospectively documented during 2013 and 2014 in a tertiary intensive care unit (ICU) and categorized as continuation, de-escalation or escalation of the empirical antimicrobial treatment. Determinants of the de-escalation or escalation treatments were identified by multivariate logistic regression; the continuation category was used as the reference group. Using systematically collected diagnostic and surveillance cultures, we estimated the cumulative incidence of antimicrobial resistance following de-escalation or continuation of therapy, with adjustment for ICU discharge and death as competing risks. Of 478 anti-pseudomonal antibiotic prescriptions, 42 (9 %) were classified as escalation of the antimicrobial treatment and 121 (25 %) were classified as de-escalation, mainly through replacement of the originally prescribed antibiotics with those having a narrower spectrum. In multivariate analysis, de-escalation was associated with the identification of etiologic pathogens (p antibiotic course in the ICU in de-escalated versus continued prescriptions was 8 (range 6-10) versus 5 (range 4-7) days, respectively (p resistance to the initial beta-lactam antibiotic on day 14 were 30.6 and 23.5 % for de-escalation and continuation, respectively (p = 0.22). For the selection of multi-drug resistant pathogens, these values were 23.5 (de-escalation) and 18.6 % (continuation) respectively (p = 0.35). The emergence of antibiotic-resistant bacteria after exposure to anti-pseudomonal beta-lactam antibiotics was not lower following de-escalation.

  13. Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data.

    Science.gov (United States)

    Bailly, Sébastien; Leroy, Olivier; Montravers, Philippe; Constantin, Jean-Michel; Dupont, Hervé; Guillemot, Didier; Lortholary, Olivier; Mira, Jean-Paul; Perrigault, Pierre-François; Gangneux, Jean-Pierre; Azoulay, Elie; Timsit, Jean-François

    2015-11-01

    Systemic antifungal therapy (SAT) of invasive candidiasis needs to be initiated immediately upon clinical suspicion. Controversies exist about adequate time and potential harm of antifungal de-escalation (DE) in documented and suspected candidiasis in ICU patients. Our objective was to investigate whether de-escalation within 5 days of antifungal initiation is associated with an increase of the 28-day mortality in SAT-treated non-neutropenic adult ICU patients. From the 835 non-neutropenic adults recruited in the multicenter prospective observational AmarCAND2 study, we selected the patients receiving systemic antifungal therapy for a documented or suspected invasive candidiasis in the ICU and who were still alive 5 days after SAT initiation. They were included into two groups according to the occurrence of observed SAT de-escalation before day 6. The average causal SAT de-escalation effect on 28-day mortality was evaluated by using a double robust estimation. Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22%), including 48 (34%) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de-escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95% CI 0.76-1.66). In non-neutropenic critically ill adult patients with documented or suspected invasive candidiasis, SAT de-escalation within 5 days was not related to increased day-28 mortality but it was associated with decreased SAT consumption. These results suggest for the first time that SAT de-escalation may be safe in these patients.

  14. The role of motivation, responsibility, and integrative complexity in crisis escalation: comparative studies of war and peace crises.

    Science.gov (United States)

    Winter, David G

    2007-05-01

    Drawing on D. G. Winter's (1993) comparison of 1914 and the Cuban Missile Crisis, the author identified 8 paired crises (1 escalating to war, 1 peacefully resolved). Documents (diplomatic messages, speeches, official media commentary) from each crisis were scored for power, affiliation, and achievement motivation; text measures of responsibility and activity inhibition; and integrative complexity. Aggregated effect-size results show that war crises had significantly higher levels of power motivation and responsibility, whereas peace crises showed trends toward higher integrative complexity and achievement motivation. Follow-up analyses suggested that these results are robust with respect to both sides in a crisis, type of material scored, and historical time. The power motive results extend previous findings, but the responsibility results suggest that responsibility plays a paradoxical role in war. Future research directions are sketched, and the role of psychological content analysis in monitoring the danger of war is discussed. ((c) 2007 APA, all rights reserved).

  15. Multicenter, Phase 1, Dose Escalation Study of Hypofractionated Stereotactic Radiation Therapy With Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma.

    Science.gov (United States)

    Clarke, Jennifer; Neil, Elizabeth; Terziev, Robert; Gutin, Philip; Barani, Igor; Kaley, Thomas; Lassman, Andrew B; Chan, Timothy A; Yamada, Josh; DeAngelis, Lisa; Ballangrud, Ase; Young, Robert; Panageas, Katherine S; Beal, Kathryn; Omuro, Antonio

    2017-11-15

    To establish the maximum tolerated dose of a 3-fraction hypofractionated stereotactic reirradiation schedule when delivered with concomitant bevacizumab to treat recurrent high-grade gliomas. Patients with recurrent high-grade glioma with Karnofsky performance status ≥60, history of standard fractionated initial radiation, tumor volume at recurrence ≤40 cm3, and absence of brainstem or corpus callosum involvement were eligible. A standard 3+3 phase 1 dose escalation trial design was utilized, with dose-limiting toxicities defined as any grade 3 to 5 toxicities possibly, probably, or definitely related to radiation. Bevacizumab was given at a dose of 10 mg/kg every 2 weeks. Hypofractionated stereotactic reirradiation was initiated after 2 bevacizumab doses, delivered in 3 fractions every other day, starting at 9 Gy per fraction. A total of 3 patients were enrolled at the 9 Gy × 3 dose level cohort, 5 in the 10 Gy × 3 cohort, and 7 in the 11 Gy × 3 cohort. One dose-limiting toxicity of grade 3 fatigue and cognitive deterioration possibly related to hypofractionated stereotactic reirradiation was observed in the 11 Gy × 3 cohort, and this dose was declared the maximum tolerated dose in combination with bevacizumab. Although no symptomatic radionecrosis was observed, substantial treatment-related effects and necrosis were observed in resected specimens. The intent-to-treat median overall survival was 13 months. Reirradiation using a 3-fraction schedule with bevacizumab support is feasible and reasonably well tolerated. Dose-escalation was possible up to 11 Gy × 3, which achieves a near doubling in the delivered biological equivalent dose to normal brain, in comparison with our previous 6 Gy × 5 schedule. Promising overall survival warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Das, Shiva [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Gu, Lin [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Dunphy, Frank R.; Ready, Neal E. [Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States)

    2015-12-01

    Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

  17. A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu [U.C. Davis School of Medicine, Department of Radiation Oncology, Sacramento, CA (United States); Ayala, Deandra; Jensen, Courtney [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Case, L. Douglas [Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Bourland, J. Daniel; Ellis, Thomas L. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); McMullen, Kevin P.; Chan, Michael D. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Tatter, Stephen B. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Lesser, Glen J. [Hematology Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Shaw, Edward G. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States)

    2012-02-01

    Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

  18. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  19. Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study.

    Science.gov (United States)

    Isakoff, S J; Wang, D; Campone, M; Calles, A; Leip, E; Turnbull, K; Bardy-Bouxin, N; Duvillié, L; Calvo, E

    2014-11-25

    This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine. Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an 'up-down' design to determine the toxicity contour of the combination. Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m(-2) twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients. In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed.

  20. A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

    Science.gov (United States)

    Thorstensson, Rigmor; Trollfors, Birger; Al-Tawil, Nabil; Jahnmatz, Maja; Bergström, Jakob; Ljungman, Margaretha; Törner, Anna; Wehlin, Lena; Van Broekhoven, Annie; Bosman, Fons; Debrie, Anne-Sophie; Mielcarek, Nathalie; Locht, Camille

    2014-01-01

    Background Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration ClinicalTrials.gov NCT01188512 PMID:24421886

  1. Causal loop diagrams as a de-escalation technique

    NARCIS (Netherlands)

    Pala, O.; Vriens, D.J.; Vennix, J.A.M.

    2015-01-01

    Escalation of commitment, the tendency of decision makers to keep on investing in losing courses of action, has been shown to be a costly decision bias that affects many areas of decision making. Even though escalation is a widely studied phenomenon, there has been comparatively little research on

  2. Nanotechnology Safety Self-Study

    Energy Technology Data Exchange (ETDEWEB)

    Grogin, Phillip W. [Los Alamos National Laboratory

    2016-03-29

    Nanoparticles are near-atomic scale structures between 1 and 100 nanometers (one billionth of a meter). Engineered nanoparticles are intentionally created and are used in research and development at Sandia National Laboratories (SNL) and Los Alamos National Laboratory (LANL). This course, Nanotechnology Safety Self-Study, presents an overview of the hazards, controls, and uncertainties associated with the use of unbound engineered nanoscale particles (UNP) in a laboratory environment.

  3. Neurobiology of escalated aggression and violence

    NARCIS (Netherlands)

    Miczek, Klaus A.; de Almeida, Rosa M. M.; Kravitz, Edward A.; Rissman, Emilie F.; de Boer, Sietse F.; Raine, Adrian

    2007-01-01

    Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and

  4. Flunking Kindergarten: Escalating Curriculum Leaves Many Behind.

    Science.gov (United States)

    Shepard, Lorrie A.; Smith, Mary Lee

    1988-01-01

    Study of kindergarten retention in Colorado reveals the following: (1) kindergarten retention does nothing to boost subsequent academic achievement; (2) regardless of what it is called, kindergarten retention creates a social stigma; and (3) kindergarten retention feeds the escalation of inappropriate academic demand in first grade. Policy…

  5. Phase I dose escalation study of concurrent palliative radiation therapy with sorafenib in three anatomical cohorts (Thorax, Abdomen, Pelvis): The TAP study.

    Science.gov (United States)

    Murray, Louise; Longo, Joseph; Wan, Jonathan; Chung, Caroline; Wang, Lisa; Dawson, Laura; Milosevic, Michael; Oza, Amit; Brade, Anthony

    2017-07-01

    To evaluate the tolerability and maximum tolerated dose (MTD) of sorafenib administered concurrently with palliative radiotherapy. In patients with incurable cancer, sorafenib was escalated independently in three cohorts based on irradiation site: thorax, abdomen or pelvis. Sorafenib was administered days 1-28 and radiotherapy (30Gy in 10 fractions) was delivered days 8-12 and 15-19. Dose-limiting toxicities (DLT) were acute grade 3+ toxicities attributable to radiotherapy. For the thorax, abdomen and pelvis cohorts, 14, 16 and 4 patients were recruited, and Dose Levels 3, 3 and 2 were reached, respectively. Sorafenib-related systemic toxicity led to significant sorafenib interruption in 10 patients. There were 3 DLTs in total, one per cohort: grade 3 oesophagitis (thoracic), transaminase elevation (abdominal) and grade 5 bowel perforation (pelvic; patient with tumour invading bowel). Grade 2 radiation dermatitis developed in 12 patients. The trial was terminated early as slow accrual and sorafenib-related systemic toxicity prevented efficient evaluation of RT-related DLTs. The MTD of sorafenib when used with 30Gy in 10 fractions was not established due to sorafenib-related systemic toxicity. Severe radiotherapy-related toxicities were also observed. These events suggest this concurrent combination does not warrant further study. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70-75 Gy in 5 weeks for advanced head and neck cancer. A phase I dose escalation study

    Energy Technology Data Exchange (ETDEWEB)

    Cvek, J.; Skacelikova, E.; Otahal, B.; Halamka, M.; Feltl, D. [University Hospital Ostrava (Czech Republic). Dept. of Oncology; Kubes, J. [University Hospital Bulovka, Prague (Czech Republic). Dept. of Radiation Oncology; Kominek, P. [University Hospital Ostrava (Czech Republic). Dept. of Otolaryngology

    2012-08-15

    Background and purpose: The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. Methods and materials: A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV{sub tumor}) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV{sub uninvolved}) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. Results: Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was {<=} 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. Conclusion: HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

  7. Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials.

    Science.gov (United States)

    Bhutta, Zulfiqar A; Capeding, Maria Rosario; Bavdekar, Ashish; Marchetti, Elisa; Ariff, Shabina; Soofi, Sajid B; Anemona, Alessandra; Habib, Muhammad A; Alberto, Edison; Juvekar, Sanjay; Khan, Rana M Qasim; Marhaba, Rachid; Ali, Noshad; Malubay, Nelia; Kawade, Anand; Saul, Allan; Martin, Laura B; Podda, Audino

    2014-02-01

    Typhoid vaccination is a public health priority in developing countries where young children are greatly affected by typhoid fever. Because present vaccines are not recommended for children younger than 2 years, the Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety of Vi-CRM197 in participants of various ages in endemic countries in south and southeast Asia. We did two randomised, observer-blind, age de-escalation, phase 2 trials at two sites in Pakistan and India (study A), and at one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012. Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12 months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer-generated randomisation list (block size of four) to receive either 5 μg Vi-CRM197 or 25 μg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate vaccine in children younger than 2 years). Both infant populations received Vi-CRM197 concomitantly with vaccines of the Expanded Programme on Immunization (EPI), according to WHO schedule. With the exception of designated study site personnel responsible for vaccine preparation, study investigators, those assessing outcomes, and data analysts were masked to treatment allocation. We specified no a-priori null hypothesis for the immunogenicity or safety objectives and all analyses were descriptive. Analyses were by modified intention-to-treat. These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and NCT01437267. 320 participants were enrolled and vaccinated in the two trials: 200 in study A (all age groups) and 120 in study B (children and infants only), of whom 317 (99%) were included in the modified intention-to-treat analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117

  8. A national evaluation of a dissemination and implementation initiative to enhance primary care practice capacity and improve cardiovascular disease care: the ESCALATES study protocol.

    Science.gov (United States)

    Cohen, Deborah J; Balasubramanian, Bijal A; Gordon, Leah; Marino, Miguel; Ono, Sarah; Solberg, Leif I; Crabtree, Benjamin F; Stange, Kurt C; Davis, Melinda; Miller, William L; Damschroder, Laura J; McConnell, K John; Creswell, John

    2016-06-29

    The Agency for Healthcare Research and Quality (AHRQ) launched the EvidenceNOW Initiative to rapidly disseminate and implement evidence-based cardiovascular disease (CVD) preventive care in smaller primary care practices. AHRQ funded eight grantees (seven regional Cooperatives and one independent national evaluation) to participate in EvidenceNOW. The national evaluation examines quality improvement efforts and outcomes for more than 1500 small primary care practices (restricted to those with fewer than ten physicians per clinic). Examples of external support include practice facilitation, expert consultation, performance feedback, and educational materials and activities. This paper describes the study protocol for the EvidenceNOW national evaluation, which is called Evaluating System Change to Advance Learning and Take Evidence to Scale (ESCALATES). This prospective observational study will examine the portfolio of EvidenceNOW Cooperatives using both qualitative and quantitative data. Qualitative data include: online implementation diaries, observation and interviews at Cooperatives and practices, and systematic assessment of context from the perspective of Cooperative team members. Quantitative data include: practice-level performance on clinical quality measures (aspirin prescribing, blood pressure and cholesterol control, and smoking cessation; ABCS) collected by Cooperatives from electronic health records (EHRs); practice and practice member surveys to assess practice capacity and other organizational and structural characteristics; and systematic tracking of intervention delivery. Quantitative, qualitative, and mixed methods analyses will be conducted to examine how Cooperatives organize to provide external support to practices, to compare effectiveness of the dissemination and implementation approaches they implement, and to examine how regional variations and other organization and contextual factors influence implementation and effectiveness. ESCALATES is

  9. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  10. De-escalation in mental health care settings: patient and staff member perspectives

    DEFF Research Database (Denmark)

    Lauge Berring, Lene; Pedersen, Liselotte; Buus, Niels

    2016-01-01

    This multiple case study explored de-escalation processes in threatening and violent situations based on patients and staff members perspectives. Our post hoc analysis indicated that de-escalation included responsive interactions influenced by the perspectives of both patients and staff members. ......-escalation can foster shared problem solving in violent and threatening situations....

  11. Escalator-related injuries in 30 dogs (2007-2014).

    Science.gov (United States)

    Pearson, Emma-Leigh; Whelan, Megan; Bracker, Kiko

    2017-07-01

    To describe a population of dogs affected by escalator-related injuries, and to characterize the types of injuries sustained and describe treatment administered. Retrospective study from March 2007 to November 2014. Large urban referral and emergency facility. Thirty client-owned dogs presenting with injuries acquired while riding an escalator. None. All injuries in this study occurred secondary to entrapment of 1 or more paws in the moving parts of an escalator; 39 paws were injured in total. The median body weight of the patients in this study was 4.25 kg, with 73.3% of the patients weighing less than 10 kg. Fifteen patients (50.0%) were treated surgically, the remainder were managed conservatively. Eight patients (26.7%) underwent digit or partial-digit amputation. Of the conservatively managed patients, 10 were treated with bandaging of the wounds. Antimicrobials, opiate analgesics, and nonsteroidal anti-inflammatory drugs were administered in both surgically and conservatively managed patients. While uncommon, escalator accidents can result in significant injury to dogs. Measures can be taken to prevent these injuries from occurring, whether through client education, dog training, structural modifications in the escalators themselves, or avoidance of escalators. In the present study, the survival rate of dogs injured on escalators was 100%. © Veterinary Emergency and Critical Care Society 2017.

  12. Efficacy and safety of urinary catheters with silver alloy coating in patients with spinal cord injury: a multicentric pragmatic randomized controlled trial. The ESCALE trial.

    Science.gov (United States)

    Bonfill, Xavier; Rigau, David; Esteban-Fuertes, Manuel; Barrera-Chacón, Juana M; Jáuregui-Abrisqueta, María L; Salvador, Sebastian; Alemán-Sánchez, Carolina M; Borau, Albert; Bea-Muñoz, Manuel; Hidalgo, Begoña; Andrade, Maria J; Espinosa, Juan R; Martínez-Zapata, María José

    2017-11-01

    Patients with spinal cord injury (SCI) who carry indwelling urinary catheters have an increased risk of urinary tract infection (UTI). Antiseptic silver alloy-coated (SAC) silicone urinary catheters prove to be a promising intervention to reduce UTIs; however, current evidence cannot be extrapolated to patients with SCI. This study aimed to assess the efficacy of SAC urinary catheters for preventing catheter-associated urinary tract infections. This is an open-label, multicenter (developed in Spain, Portugal, Chile, Turkey, and Italy), randomized clinical trial conducted in 14 hospitals from November 2012 to December 2015. Eligible patients were men or women with traumatic or medical SCI, aged ≥18 years, requiring an indwelling urinary catheter for at least 7 days. The primary outcome was the incidence of symptomatic UTIs. The secondary outcome included bacteremia in the urinary tract and adverse events. Patients were randomized to receive a SAC urinary catheter (experimental group) or a standard catheter (control group) for at least 7 days. Data were compared using chi-squared test and also calculating the absolute risk difference with a 95% confidence interval. An adjusted analysis including different risk factors of UTI was performed. This study was mainly funded by La Marató de TV3 Foundation (grant number # 112210) and the European Clinical Research Infrastructures Network organization. The funders had no role in the interpretation or reporting of results. A total of 489 patients were included in the study, aged 55 years in the experimental group and aged 57 in the control group (p=.870); 72% were men; 43% were hospitalized patients, and 57% were outpatients (p=1.0). The most frequent cause of SCI was traumatic (73.75%), and the localization was mainly the cervical spine (42.74%). Most of the patients had an A score (complete spinal injury and no motor and sensory is preserved) on the ASIA scale (62.37%). The median time of urethral catheterization was 27

  13. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma.

    Science.gov (United States)

    Wen, Patrick Y; Omuro, Antonio; Ahluwalia, Manmeet S; Fathallah-Shaykh, Hassan M; Mohile, Nimish; Lager, Joanne J; Laird, A Douglas; Tang, Jiali; Jiang, Jason; Egile, Coumaran; Cloughesy, Timothy F

    2015-09-01

    This phase I study aimed to evaluate safety, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of voxtalisib (SAR245409, XL765), a pan-class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, in combination with temozolomide (TMZ), with or without radiation therapy (RT), in patients with high-grade glioma. Patients received voxtalisib 30-90 mg once daily (q.d.) or 20-50 mg twice daily (b.i.d.), in combination with 200 mg/m(2) TMZ (n = 49), or voxtalisib 20 mg q.d. with 75 mg/m(2) TMZ and RT (n = 5). A standard 3 + 3 dose-escalation design was used to determine the maximum tolerated dose. Patients were evaluated for adverse events (AEs), plasma pharmacokinetics, pharmacodynamic effects in skin biopsies, and tumor response. The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ. The most frequently reported treatment-related AEs were nausea (48%), fatigue (43%), thrombocytopenia (26%), and diarrhea (24%). The most frequently reported treatment-related grade ≥3 AEs were lymphopenia (13%), thrombocytopenia, and decreased platelet count (9% each). Pharmacokinetic parameters were similar to previous studies with voxtalisib monotherapy. Moderate inhibition of PI3K signaling was observed in skin biopsies. Best response was partial response in 4% of evaluable patients, with stable disease observed in 68%. Voxtalisib in combination with TMZ with or without RT in patients with high-grade gliomas demonstrated a favorable safety profile and a moderate level of PI3K/mTOR pathway inhibition. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. An Open-Label, Dose-Escalation Phase I Study of Anti-TYRP1 Monoclonal Antibody IMC-20D7S for Patients with Relapsed or Refractory Melanoma.

    Science.gov (United States)

    Khalil, Danny N; Postow, Michael A; Ibrahim, Nageatte; Ludwig, Dale L; Cosaert, Jan; Kambhampati, Siva Rama Prasad; Tang, Shande; Grebennik, Dmitri; Kauh, John Sae Wook; Lenz, Heinz-Josef; Flaherty, Keith T; Hodi, F Stephen; Lawrence, Donald P; Wolchok, Jedd D

    2016-11-01

    Tyrosinase-related protein-1 (TYRP1) is a transmembrane glycoprotein that is specifically expressed in melanocytes and melanoma cells. Preclinical data suggest that mAbs targeting TYRP1 confer antimelanoma activity. IMC-20D7S is a recombinant human IgG1 mAb targeting TYRP1. Here, we report the first-in-human phase I/Ib trial of IMC-20D7S. The primary objective of this study was to establish the safety profile and the MTD of IMC-20D7S. Patients with advanced melanoma who progressed after or during at least one line of treatment or for whom standard therapy was not indicated enrolled in this standard 3 + 3 dose-escalation, open-label study. IMC-20D7S was administered intravenously every 2 or 3 weeks. Twenty-seven patients were enrolled. The most common adverse events were fatigue and constipation experienced by nine (33%) and eight (30%) patients, respectively. There were no serious adverse events related to treatment, no discontinuations of treatment due to adverse events, and no treatment-related deaths. Given the absence of dose-limiting toxicities, an MTD was not defined, but a provisional MTD was established at the 20 mg/kg every 2-week dose based on serum concentration and safety data. One patient experienced a complete response. A disease control rate, defined as stable disease or better, of 41% was observed. IMC-20D7S is well tolerated among patients with advanced melanoma with evidence of antitumor activity. Further investigation of this agent as monotherapy in selected patients or as part of combination regimens is warranted. Clin Cancer Res; 22(21); 5204-10. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Directory of Open Access Journals (Sweden)

    Jérémie Rudant

    Full Text Available Genome-wide association studies (GWAS have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL. These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable. Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012, breastfeeding p = 0.017 and repeated early common infections (p = 0.0070, with allelic odds ratios (OR which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4, those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5 and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8. The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018 in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by

  16. Final results of a phase I dose-escalation, dose-expansion study of adding disulfiram with or without copper to adjuvant temozolomide for newly diagnosed glioblastoma.

    Science.gov (United States)

    Huang, Jiayi; Campian, Jian L; Gujar, Amit D; Tsien, Christina; Ansstas, George; Tran, David D; DeWees, Todd A; Lockhart, A Craig; Kim, Albert H

    2018-01-27

    Disulfiram has shown promising activity including proteasome inhibitory properties and synergy with temozolomide in preclinical glioblastoma (GBM) models. In a phase I study for newly diagnosed GBM after chemoradiotherapy, we have previously reported our initial dose-escalation results combining disulfiram with adjuvant temozolomide and established the maximum tolerated dose (MTD) as 500 mg per day. Here we report the final results of the phase I study including an additional dose-expansion cohort of disulfiram with concurrent copper. The phase I study consisted of an initial dose-escalation phase of disulfiram 500-1000 mg daily during adjuvant temozolomide, followed by a dose-expansion phase of disulfiram 500 mg daily with copper 2 mg three times daily. Proteasome inhibition was assessed using fluorometric 20S proteasome assay on peripheral blood cell. A total of 18 patients were enrolled: 7 patients received 500 mg disulfiram, 5 patients received 1000 mg disulfiram, and 6 patients received 500 mg disulfiram with copper. Two dose-limiting toxicities occurred with 1000 mg disulfiram. At disulfiram 500 mg with or without copper, only 1 patient (7%) required dose-reduction during the first month of therapy. Addition of copper to disulfiram did not increase toxicity nor proteasome inhibition. The median progression-free survival was 4.5 months (95% CI 0.8-8.2). The median overall survival (OS) was 14.0 months (95% CI 8.3-19.6), and the 2-year OS was 24%. The MTD of disulfiram at 500 mg daily in combination with adjuvant temozolomide was well tolerated by GBM patients, but 1000 mg daily was not. Toxicity and pharmacodynamic effect of disulfiram were similar with or without concurrent copper. The clinical efficacy appeared to be comparable to historical data. Additional clinical trials to combine disulfiram and copper with chemoradiotherapy or to resensitize recurrent GBM to temozolomide are ongoing.

  17. First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.

    Science.gov (United States)

    Rolan, Paul E; O'Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

    2015-01-01

    To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was

  18. Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Leonard, Kara Lynne [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States); Safran, Howard [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Ng, Thomas [Division of Thoracic Surgery, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Taber, Angela [Division of Medical Oncology, Miriam Hospital, Brown University, Providence, Rhode Island (United States); Khurshid, Humera; Birnbaum, Ariel [Division of Medical Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Wazer, David E.; DiPetrillo, Thomas [Department of Radiation Oncology, Rhode Island Hospital, Brown University, Providence, Rhode Island (United States); Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts (United States)

    2016-12-01

    Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24

  19. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Directory of Open Access Journals (Sweden)

    Marincek Nicolas

    2013-01-01

    Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

  20. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

    Science.gov (United States)

    Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

    2013-01-15

    We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

  1. Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study.

    Science.gov (United States)

    Závada, Jakub; Uher, Michal; Svobodová, Radka; Olejárová, Marta; Hušáková, Markéta; Ciferská, Hana; Hulejová, Hana; Tomčík, Michal; Šenolt, Ladislav; Vencovský, Jiří

    2015-11-25

    The aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE). Serum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3-6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially. We examined cross-sectionally the relationships between serum concentrations of TNC and SLE status, SLEDAI-2 K scores, strata of disease activity, and levels of conventional biomarkers [anti-double-stranded DNA (dsDNA), anti-nucleosome antibodies, C3 and C4]. We also explored the utility of TNC levels for predicting disease flares, defined as (i) new/increased GC, (ii) new/increased GC or IS, and (iii) increase in SLEDAI by ≥3 or (iv) BILAG A or B flare. There was no significant difference in the mean levels of TNC between the SLE patients and HC. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the HC (p = 0.004) or in patients with no/low disease activity (p = 0.004). In SLE patients, TNC levels were significantly associated with positivity of anti-dsDNA (p = 0.03) and anti-nucleosome antibodies (p = 0.008). Flares defined by a need to escalate immunosuppressive therapy were captured more frequently and earlier than flares defined by standard activity indices. Higher baseline levels of serum TNC presented a significantly greater risk of flare (i) [hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.73] or (ii) (HR 1.25, 95

  2. A Phase 1 Study of Stereotactic Body Radiation Therapy Dose Escalation for Borderline Resectable Pancreatic Cancer After Modified FOLFIRINOX (NCT01446458)

    Energy Technology Data Exchange (ETDEWEB)

    Shaib, Walid L.; Hawk, Natalyn [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Cassidy, Richard J. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Chen, Zhengjia; Zhang, Chao [Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Brutcher, Edith [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Kooby, David; Maithel, Shishir K.; Sarmiento, Juan M. [Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Landry, Jerome [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel F., E-mail: bassel.el-rayes@emoryhealthcare.org [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2016-10-01

    Purpose: A challenge in borderline resectable pancreatic cancer (BRPC) management is the high rate of positive posterior margins (PM). Stereotactic body radiation therapy (SBRT) allows for higher radiation delivery dose with conformity. This study evaluated the maximal tolerated dose with a dose escalation plan level up to 45 Gy using SBRT in BRPC. Methods and Materials: A single-institution, 3 + 3 phase 1 clinical trial design was used to evaluate 4 dose levels of SBRT delivered in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost (SIB) to the PM. Dose level (DL) 1 was 30 Gy to the PTV, and for dose levels 2 through 4 (DL2-DL4) the dose was 36 Gy. The SIB dose to the PM was 6, 6, 7.5, and 9 Gy for DL-1, DL-2, DL-3, and DL-4, respectively. All patients received 4 treatments of modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) before SBRT. Results: Thirteen patients with a median age of 64 years were enrolled. The median follow-up time was 18 months. The locations of the cancer were head (n=12) and uncinate/neck (n=1). One patient did not undergo SBRT. There were no grade 3 or 4 toxicities. Five patients did not undergo resection because of disease progression (1 local, 4 distant); 8 had R0 resection in the PM, and 5 of 8 had vessel reconstruction. Two patients had disease downstaged to T1 and T2 from T3 disease. Four patients are still alive, and 3 are disease free. The median overall survival for resected patients was not reached (9.3: not reached). Conclusion: The SBRT dose of 36 Gy with a 9-Gy SIB to the PM (total 45 Gy) delivered in 3 fractions is safe and well tolerated. The dose-limiting toxicity for a 45-Gy dose was not reached, and further dose escalations are needed in future trials.

  3. Learning and performance outcomes of mental health staff training in de-escalation techniques for the management of violence and aggression.

    Science.gov (United States)

    Price, Owen; Baker, John; Bee, Penny; Lovell, Karina

    2015-06-01

    De-escalation techniques are a recommended non-physical intervention for the management of violence and aggression in mental health. Although taught as part of mandatory training for all National Health Service (NHS) mental health staff, there remains a lack of clarity around training effectiveness. To conduct a systematic review of the learning, performance and clinical safety outcomes of de-escalation techniques training. The review process involved a systematic literature search of 20 electronic databases, eligibility screening of results, data extraction, quality appraisal and data synthesis. A total of 38 relevant studies were identified. The strongest impact of training appears to be on de-escalation-related knowledge, confidence to manage aggression and deescalation performance (although limited to artificial training scenarios). No strong conclusions could be drawn about the impact of training on assaults, injuries, containment and organisational outcomes owing to the low quality of evidence and conflicting results. It is assumed that de-escalation techniques training will improve staff's ability to de-escalate violent and aggressive behaviour and improve safety in practice. There is currently limited evidence that this training has these effects. © The Royal College of Psychiatrists 2015.

  4. Neurobiology of Escalated Aggression and Violence

    Science.gov (United States)

    Miczek, Klaus A.; de Almeida, Rosa M. M.; Kravitz, Edward A.; Rissman, Emilie F.; de Boer, Sietse F.; Raine, Adrian

    2009-01-01

    Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and its escalation with greater precision; second, the prefrontal cortex (PFC) and brainstem structures emerge as pivotal nodes in the limbic circuitry mediating escalated aggressive behavior. The neurochemical and molecular work focuses on the genes that enable invertebrate aggression in males and females and genes that are expressed or suppressed as a result of aggressive experiences in mammals. The fruitless gene, immediate early genes in discrete serotonin neurons, or sex chromosome genes identify sexually differentiated mechanisms for escalated aggression. Male, but not female, fruit flies establish hierarchical relationships in fights and learn from previous fighting experiences. By manipulating either the fruitless or transformer genes in the brains of male or female flies, patterns of aggression can be switched with males using female patterns and vice versa. Work with Sts or Sry genes suggests so far that other genes on the X chromosomes may have a more critical role in female mouse aggression. New data from feral rats point to the regulatory influences on mesocortical serotonin circuits in highly aggressive animals via feedback to autoreceptors and via GABAergic and glutamatergic inputs. Imaging data lead to the hypothesis that antisocial, violent, and psychopathic behavior may in part be attributable to impairments in some of the brain structures (dorsal and ventral PFC, amygdala, and angular gyrus) subserving moral cognition and emotion. PMID:17978016

  5. Group theories: relevance to group safety studies.

    Science.gov (United States)

    Benevento, A L

    1998-01-01

    Promoting safety in the workplace has been attempted in a variety of ways. Increasingly, industries are using groups such as safety teams and quality circles to promote worker safety. Group influences on individual behavior and attitudes have long been studied in the social psychology literature, but the theories have not been commonly found outside the psychology arena. This paper describes the group theories of group polarization, risky shift, social loafing, groupthink and team think and attempts to apply these theories to existing studies that examine work group influences on safety. Interesting parallels were found but only one study examined group influences as their primary focus of research. Since groups are increasingly used for safety promotion, future research on safety that studies group influences with respect to current group theories is recommended.

  6. Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults.

    Science.gov (United States)

    Green, C A; Scarselli, E; Voysey, M; Capone, S; Vitelli, A; Nicosia, A; Cortese, R; Thompson, A J; Sande, C S; de Lara, Catherine; Klenerman, P; Pollard, A J

    2015-10-28

    Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults. Heterologous and homologous 'prime'/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18-50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60-75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK. RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere to International Conference on Harmonisation (ICH) Good Clinical

  7. Effective ingredients of verbal de-escalation: validating an English modified version of the 'De-Escalating Aggressive Behaviour Scale'.

    Science.gov (United States)

    Mavandadi, V; Bieling, P J; Madsen, V

    2016-08-01

    WHAT IS KNOWN ON THE SUBJECT?: Verbal de-escalation is an intervention aimed at calmly managing an agitated client to prevent violence. Effective de-escalation can help reduce the use of seclusion and restraint in psychiatric settings. Despite its importance in practice, there is little agreement on the necessary techniques of de-escalation and most of the research on the topic is based on expert opinion. To our knowledge, only one attempt at quantifying de-escalation skill has been pursued through the German-language De-Escalating Aggressive Behaviour Scale (DABS). While the DABS identified seven qualities necessary for de-escalation, it has not been validated in English and may lack important descriptors. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The present study enhanced the original DABS with best, acceptable and least desirable staff de-escalation practice descriptions for each of the seven items. This enhancement of the DABS lead to the creation of the English modified DABS (EMDABS). The EMDABS was psychometrically validated for use in research and practice: raters could use the EMDABS with a high level of agreement and consistency. Also, the scale appeared to measure a single cohesive construct - de-escalation. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: With further validation, the EMDABS has potential to be the first English quantitative measure of de-escalation. The EMDABS offers seven items, with associated best practice descriptions, that may be used to inform de-escalation practice. The EMDABS can be used to evaluate training and education programmes and inform how these programmes and independent de-escalation practice may be improved. Introduction Verbal de-escalation is crucial to a non-coercive psychiatric environment. Despite its importance, the literature on de-escalation is sparse and mostly qualitative. To address this, Nau et al. (2009) quantified de-escalation by creating the German-language De-Escalating Aggressive Behaviour Scale (DABS

  8. Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France).

    Science.gov (United States)

    Bailey, Helen D; Rios, Paula; Lacour, Brigitte; Guerrini-Rousseau, Léa; Bertozzi, Anne-Isabelle; Leblond, Pierre; Faure-Conter, Cécile; Pellier, Isabelle; Freycon, Claire; Michon, Jean; Puget, Stéphanie; Ducassou, Stéphane; Orsi, Laurent; Clavel, Jacqueline

    2017-04-15

    Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes. © 2017 UICC.

  9. Treatment assignment guesses by study participants in a double-blind dose escalation clinical trial of saw palmetto.

    Science.gov (United States)

    Lee, Jeannette Y; Moore, Page; Kusek, John; Barry, Michael

    2014-01-01

    This report assesses participant perception of treatment assignment in a randomized, double-blind, placebo-controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia (BCM). Participants randomized to receive saw palmetto were instructed to take one 320 mg gelcap daily for the first 24 weeks, two 320 mg gelcaps daily for the second 24 weeks, and three 320 mg gelcaps daily for the third 24 weeks. Study participants assigned to placebo were instructed to take the same number of matching placebo gelcaps in each time period. At 24, 48, and 72 weeks postrandomization, the American Urological Association Symptom Index (AUA-SI) was administered and participants were asked to guess their treatment assignment. The study was conducted at 11 clinical centers in North America. Study participants were men, 45 years and older, with moderate to low severe BPH symptoms, randomized to saw palmetto (N=151) or placebo (N=155). Treatment arms were compared with respect to the distribution of participant guesses of treatment assignment. For participants assigned to saw palmetto, 22.5%, 24.7%, and 29.8% correctly thought they were taking saw palmetto, and 37.3%, 40.0%, and 44.4% incorrectly thought they were on placebo at 24, 48, and 72 weeks, respectively. For placebo participants, 21.8%, 27.4%, and 25.2% incorrectly thought they were on saw palmetto, and 41.6%, 39.9%, and 42.6% correctly thought they were on placebo at 24, 48, and 72 weeks, respectively. The treatment arms did not vary with respect to the distributions of participants who guessed they were on saw palmetto (p=0.823) or placebo (p=0.893). Participants who experienced an improvement in AUA-SI were 2.16 times more likely to think they were on saw palmetto. Blinding of treatment assignment was successful in this study. Improvement in BPH-related symptoms was associated with the perception that participants were taking saw palmetto.

  10. A Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications

    Science.gov (United States)

    2017-08-30

    Colorectal Cancer (CRC); Ovarian Cancer (Epithelial and Fallopian Tube ); Urothelial Carcinoma; Triple-negative Breast Cancer (TNBC); Pancreatic Cancer; Acute Myeloid Leukemia/Myelodysplastic Syndrome; Multiple Myeloma (MM)

  11. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study

    DEFF Research Database (Denmark)

    Coiffier, B.; Lepretre, S.; Pedersen, L.M.

    2008-01-01

    Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B), and 27 (C) patients received 4, once weekly, infusio...

  12. A phase 1 dose-escalation study of the oral histone deacetylase inhibitor abexinostat in combination with standard hypofractionated radiotherapy in advanced solid tumors

    Science.gov (United States)

    Deutsch, Eric; Moyal, Elizabeth Cohen-Jonathan; Gregorc, Vanesa; Zucali, Paolo Andrea; Menard, Jean; Soria, Jean-Charles; Kloos, Ioana; Hsu, Jeff; Luan, Ying; Liu, Emily; Vezan, Remus; Graef, Thorsten; Rivera, Sofia

    2017-01-01

    Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting. Among 58 treated patients, the median age was 61.5 years (range, 20-82); 47% of the patients had M1 stage disease, and 95% had received previous chemotherapy alone or chemotherapy in combination with surgery and/or radiotherapy. The recommended phase 2 dose was determined to be 90 mg/m2 (140 mg). Of the 51 patients evaluable for response, best overall response was 8% (1 complete response [CR], 3 partial responses [PRs]), and best loco-regional response was 12% (1 CR and 5 PRs) at a median follow-up of 16 weeks. Of note, patients with target or non-target brain lesions showed encouraging responses, with 1 patient achieving a best loco-regional response of CR. Treatment-emergent grade ≥3 adverse events (AEs) were few, with most common being thrombocytopenia (17%), lymphopenia (12%), and hypokalemia (7%). Six patients (10%) discontinued treatment due to AEs. No grade ≥3 prolongation of the QTc interval was observed, with no treatment discontinuations due to this AE. Oral abexinostat combined with radiotherapy was well tolerated in patients with advanced solid tumors. The combination may have potential for treatment of patients with brain lesions. PMID:28915584

  13. Flammable Gas Safety Self-Study 52827

    Energy Technology Data Exchange (ETDEWEB)

    Glass, George [Los Alamos National Laboratory

    2016-03-17

    This course, Flammable Gas Safety Self-Study (COURSE 52827), presents an overview of the hazards and controls associated with commonly used, compressed flammable gases at Los Alamos National Laboratory (LANL).

  14. Requirements of a new communication technology for handover and the escalation of patient care: a multi-stakeholder analysis.

    Science.gov (United States)

    Johnston, Maximilian J; King, Dominic; Arora, Sonal; Cooper, Kerri; Panda, Neha Aparajita; Gosling, Rebecca; Singh, Kaushiki; Sanders, Bradley; Cox, Benita; Darzi, Ara

    2014-08-01

    In order to enable safe and efficient information transfer between health care professionals during clinical handover and escalation of care, existing communication technologies must be updated. This study aimed to provide a user-informed guide for the development of an application-based communication system (ABCS), tailored for use in patient handover and escalation of care. Current methods of inter-professional communication in health care along with information system needs for communication technology were identified through literature review. A focus group study was then conducted according to a topic guide developed by health innovation and safety researchers. Fifteen doctors and 11 nurses from three London hospitals participated in a mixture of homogeneous and heterogeneous sessions. The sessions were recorded and transcribed verbatim before being subjected to thematic analysis. Seventeen information system needs were identified from the literature review. Participants identified six themes detailing user perceptions of current communication technology, attitudes to smartphone technology and anticipated requirements of an application produced for handover and escalation of care. Participants were in favour of an ABCS over current methods and expressed enthusiasm for a system with integrated patient information and group-messaging functions. Despite concerns regarding confidentiality and information governance a robust guide for development and implementation of an ABCS was produced, taking input from multiple stakeholders into account. Handover and escalation of care are vital processes for patient safety and communication within these must be optimized. An ABCS for health care professionals would be a welcome innovation and may lead to improvements in patient safety. © 2014 John Wiley & Sons, Ltd.

  15. Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Michelle M., E-mail: michekim@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Camelo-Piragua, Sandra [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew; Tao, Yebin [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Junck, Larry; Mammoser, Aaron [Department of Neurology, University of Michigan, Ann Arbor, Michigan (United States); Betz, Bryan L. [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States); Kim, Christopher J. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Heth, Jason; Sagher, Oren [Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

    2016-02-01

    Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

  16. Criticality safety basics, a study guide

    Energy Technology Data Exchange (ETDEWEB)

    V. L. Putman

    1999-09-01

    This document is a self-study and classroom guide, for criticality safety of activities with fissile materials outside nuclear reactors. This guide provides a basic overview of criticality safety and criticality accident prevention methods divided into three parts: theory, application, and history. Except for topic emphasis, theory and history information is general, while application information is specific to the Idaho National Engineering and Environmental Laboratory (INEEL). Information presented here should be useful to personnel who must know criticality safety basics to perform their assignments safely or to design critically safe equipment or operations. However, the guide's primary target audience is fissile material handler candidates.

  17. Predicting Responses to Bids for Sexual and Romantic Escalation in Cross-Sex Friendships.

    Science.gov (United States)

    Akbulut, Valerie; Weger, Harry

    2016-01-01

    The transition from a platonic cross-sex friendship to a more intimate sexual and/or romantic relationship is an interesting, yet somewhat understudied, phenomenon. In this study, we introduce and test relationship adaptation theory to predict cross-sex friends' predispositions for reciprocating a bid for escalation to an exclusive dating or friends with benefits (FWB) relationship. Analyses of data collected from 288 participants found participants' dating status, anticipated rewards from escalating the relationship, expected social disapproval, friendship quality, and their friend's attractiveness predicted disposition to reciprocating a cross-sex friend's hypothetical bid for escalation to an exclusive romantic escalation. In addition, participants' biological sex, anticipated rewards from escalating the relationship, expected social disapproval, sexual permissiveness, and their friend's attractiveness emerged as predictors of disposition toward a friend's hypothetical bid to escalate a platonic friendship to a FWB relationship.

  18. Safety assessment in plant layout design using indexing approach: implementing inherent safety perspective. Part 2-Domino Hazard Index and case study.

    Science.gov (United States)

    Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

    2008-12-15

    The design of layout plans requires adequate assessment tools for the quantification of safety performance. The general focus of the present work is to introduce an inherent safety perspective at different points of the layout design process. In particular, index approaches for safety assessment and decision-making in the early stages of layout design are developed and discussed in this two-part contribution. Part 1 (accompanying paper) of the current work presents an integrated index approach for safety assessment of early plant layout. In the present paper (Part 2), an index for evaluation of the hazard related to the potential of domino effects is developed. The index considers the actual consequences of possible escalation scenarios and scores or ranks the subsequent accident propagation potential. The effects of inherent and passive protection measures are also assessed. The result is a rapid quantification of domino hazard potential that can provide substantial support for choices in the early stages of layout design. Additionally, a case study concerning selection among various layout options is presented and analyzed. The case study demonstrates the use and applicability of the indices developed in both parts of the current work and highlights the value of introducing inherent safety features early in layout design.

  19. Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study

    DEFF Research Database (Denmark)

    Møller, Ditte Sloth; Nielsen, Tine Bjørn; Brink, Carsten

    2017-01-01

    -escalation driven by FDG-avid volumes, while respecting normal tissue constraints and requiring no increase in mean lung dose. Dose-escalation driven by FDG-avid volumes, delivering mean doses of 95 Gy (tumour) and 74 Gy (lymph nodes), was pursued and compared to standard 66 Gy/33 F plans. Material and methods......: Dose plans for the first thirty patients enroled were analysed. Standard and escalated plans were created for all patients, blinded to randomization, and compared for each patient in terms of the ability to escalate while protecting normal tissue. Results: The median dose-escalation in FDG-avid areas...... received doses between 66 and 74 Gy due to escalation. Conclusions: FDG-driven inhomogeneous dose-escalation achieves large increment in tumour and lymph node dose, while delivering similar doses to normal tissue as homogenous standard plans....

  20. Cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor inhibitors across Europe.

    Science.gov (United States)

    Holden, Sarah E; Currie, Craig J; Lennon, Martin; Reynolds, Alan V; Moots, Robert J

    2016-01-01

    The aim of this study was to calculate the marginal cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor (TNF) inhibitors across Europe. The proportion of people who escalate their dose of TNF inhibitor and the average percentage increase in TNF inhibitor cost associated with escalators versus non-escalators was calculated from previously published estimates, weighted by the sample size for each study. The number of people with rheumatoid arthritis treated with TNF inhibitors and the corresponding total drug sales were obtained for five European countries from Decision Resources' Pharmacor Market Forecast. Method 1 assumed that total sales of a TNF inhibitor represented the cost of an escalator multiplied by the number of escalators plus the cost of a non-escalator multiplied by the number of non-escalators. Method 2 assumed that the drug cost per day used to forecast total sales was calculated using the dose of TNF inhibitor used by non-escalators. The marginal cost of TNF inhibitor dose escalation was estimated by multiplying the difference in cost between escalators and non-escalators by the number of escalators. The estimated increase in TNF inhibitor costs associated with dose escalation in people with rheumatoid arthritis across five European countries (Germany, France, UK, Spain and Italy) was €51.5-54.4 million for adalimumab, €44.8-52.8 million for infliximab and €5.8-5.9 million for etanercept. Dose escalation of the TNF inhibitors adalimumab, etanercept and infliximab in people with rheumatoid arthritis has resulted in an increase in TNF inhibitor costs across five European countries.

  1. Study Abroad Programs: Making Safety a Priority

    Science.gov (United States)

    Buddan, Michael Craig; Budden, Connie B.; Juban, Rusty; Baraya, Aristides

    2014-01-01

    Increasingly, students are participating in study abroad programs. Such programs provide participants a variety of learning experiences. Developing cross-cultural appreciation, communication skills, maturity and a less ethno-centric mindset are among the impacts study abroad programs offer. However, care must be taken to assure student safety and…

  2. Water and Wastewater Annual Price Escalation Rates for Selected Cities across the United States

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2017-10-27

    Pacific Northwest National Laboratory conducted this study for the Federal Energy Management Program to identify trends in annual water and wastewater price escalation rates across the United States. This study can be used to inform the selection of an appropriate escalation rates for inclusion in LCCA.

  3. Railway safety climate: a study on organizational development.

    Science.gov (United States)

    Cheng, Yung-Hsiang

    2017-09-07

    The safety climate of an organization is considered a leading indicator of potential risk for railway organizations. This study adopts the perceptual measurement-individual attribute approach to investigate the safety climate of a railway organization. The railway safety climate attributes are evaluated from the perspective of railway system staff. We identify four safety climate dimensions from exploratory factor analysis, namely safety communication, safety training, safety management and subjectively evaluated safety performance. Analytical results indicate that the safety climate differs at vertical and horizontal organizational levels. This study contributes to the literature by providing empirical evidence of the multilevel safety climate in a railway organization, presents possible causes of the differences under various cultural contexts and differentiates between safety climate scales for diverse workgroups within the railway organization. This information can be used to improve the safety sustainability of railway organizations and to conduct safety supervisions for the government.

  4. Phase I study of continuous MKC-1 in patients with advanced or metastatic solid malignancies using the modified Time-to-Event Continual Reassessment Method (TITE-CRM) dose escalation design.

    Science.gov (United States)

    Tevaarwerk, Amye; Wilding, George; Eickhoff, Jens; Chappell, Rick; Sidor, Carolyn; Arnott, Jamie; Bailey, Howard; Schelman, William; Liu, Glenn

    2012-06-01

    MKC-1 is an oral cell-cycle inhibitor with broad antitumor activity in preclinical models. Clinical studies demonstrated modest antitumor activity using intermittent dosing schedule, however additional preclinical data suggested continuous dosing could be efficacious with additional effects against the mTor/AKT pathway. The primary objectives were to determine the maximum tolerated dose (MTD) and response of continuous MKC-1. Secondary objectives included characterizing the dose limiting toxicities (DLTs) and pharmacokinetics (PK). Patients with solid malignancies were eligible, if they had measurable disease, ECOG PS ≤1, and adequate organ function. Exclusions included brain metastases and inability to receive oral drug. MKC-1 was dosed twice daily, continuously in 28-day cycles. Other medications were eliminated if there were possible drug interactions. Doses were assigned using a TITE-CRM algorithm following enrollment of the first 3 pts. Disease response was assessed every 8 weeks. Between 5/08-9/09, 24 patients enrolled (15 M/9 F, median 58 years, range 44-77). Patients 1-3 received 120 mg/d of MKC-1; patients 4-24 were dosed per the TITE-CRM algorithm: 150 mg [n = 1], 180 [2], 200 [1], 230 [1], 260 [5], 290 [6], 320 [5]. The median time on drug was 8 weeks (range 4-28). The only DLT occurred at 320 mg (grade 3 fatigue). Stable disease occurred at 150 mg/d (28 weeks; RCC) and 320 mg/d (16 weeks; breast, parotid). Escalation halted at 320 mg/d. Day 28 pharmacokinetics indicated absorption and active metabolites. Continuous MKC-1 was well-tolerated; there were no RECIST responses, although clinical benefit occurred in 3/24 pts. Dose escalation stopped at 320 mg/d, and this is the MTD as defined by the CRM dose escalation algorithm; this cumulative dose/cycle exceeds that determined from intermittent dosing studies. A TITE-CRM allowed for rapid dose escalation and was able to account for late toxicities with continuous dosing via a modified algorithm.

  5. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Swisher-McClure, Samuel, E-mail: Swisher-Mcclure@uphs.upenn.edu [Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Leonard Davis Institute of Health Economics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita; Woo, Kaitlin [Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Smaldone, Marc; Uzzo, Robert [Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA (United States); Bekelman, Justin E. [Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Leonard Davis Institute of Health Economics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States); Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2014-05-01

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.

  6. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial.

    Science.gov (United States)

    Palfi, Stéphane; Gurruchaga, Jean Marc; Ralph, G Scott; Lepetit, Helene; Lavisse, Sonia; Buttery, Philip C; Watts, Colin; Miskin, James; Kelleher, Michelle; Deeley, Sarah; Iwamuro, Hirokazu; Lefaucheur, Jean Pascal; Thiriez, Claire; Fenelon, Gilles; Lucas, Cherry; Brugières, Pierre; Gabriel, Inanna; Abhay, Kou; Drouot, Xavier; Tani, Naoki; Kas, Aurelie; Ghaleh, Bijan; Le Corvoisier, Philippe; Dolphin, Patrice; Breen, David P; Mason, Sarah; Guzman, Natalie Valle; Mazarakis, Nicholas D; Radcliffe, Pippa A; Harrop, Richard; Kingsman, Susan M; Rascol, Olivier; Naylor, Stuart; Barker, Roger A; Hantraye, Philippe; Remy, Philippe; Cesaro, Pierre; Mitrophanous, Kyriacos A

    2014-03-29

    Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease. We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10(7) transducing units [TU]); mid dose (4·0×10(7) TU); and high dose (1×10(8) TU). Inclusion criteria were age 48-65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439. 15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on-off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part

  7. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.

    Science.gov (United States)

    Brown, Randall T; Nicholas, Christopher R; Cozzi, Nicholas V; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Thomas, Chantelle D; Hetzel, Scott J; Henriquez, Kelsey M; Ribaudo, Alexandra S; Hutson, Paul R

    2017-03-28

    Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods. No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied. The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose. NCT02163707.

  8. Studies on Labour Safety in Construction Sites.

    Science.gov (United States)

    Kanchana, S; Sivaprakash, P; Joseph, Sebastian

    2015-01-01

    Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites.

  9. Studies on Labour Safety in Construction Sites

    Directory of Open Access Journals (Sweden)

    S. Kanchana

    2015-01-01

    Full Text Available Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites.

  10. Medication safety research by observational study design.

    Science.gov (United States)

    Lao, Kim S J; Chui, Celine S L; Man, Kenneth K C; Lau, Wallis C Y; Chan, Esther W; Wong, Ian C K

    2016-06-01

    Observational studies have been recognised to be essential for investigating the safety profile of medications. Numerous observational studies have been conducted on the platform of large population databases, which provide adequate sample size and follow-up length to detect infrequent and/or delayed clinical outcomes. Cohort and case-control are well-accepted traditional methodologies for hypothesis testing, while within-individual study designs are developing and evolving, addressing previous known methodological limitations to reduce confounding and bias. Respective examples of observational studies of different study designs using medical databases are shown. Methodology characteristics, study assumptions, strengths and weaknesses of each method are discussed in this review.

  11. Pressure Safety: Advanced Self-Study 30120

    Energy Technology Data Exchange (ETDEWEB)

    Glass, George [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-29

    Pressure Safety Advance Self-Study (Course 30120) consists of an introduction, five modules, and a quiz. To receive credit in UTrain for completing this course, you must score 80% or better on the 15-question quiz (check UTrain). Directions for initiating the quiz are appended to the end of this training manual. This course contains several links to LANL websites. UTrain might not support active links, so please copy links into the address line in your browser.

  12. Measuring Safety Culture on Ships Using Safety Climate: A Study among Indian Officers

    Directory of Open Access Journals (Sweden)

    Yogendra Bhattacharya

    2015-12-01

    Full Text Available Workplace safety continues to be an area of concern in the maritime industry due to the international nature of the operations. The effectiveness of extensive legislation to manage shipboard safety remains in doubt. The focus must therefore shift towards the human element - seafarers and their perceptions of safety. The study aims to understand the alignment that exists between safety culture and safety climate on board ships as perceived by seafarers. The underlying factors of safety climate were identified using factor analysis which isolated seven factors - Support on Safety, Organizational Support, Resource Availability, Work Environment, Job Demands, ‘Just’ Culture, and Safety Compliance. The perception of safety level of seafarers was found to be low indicating the existence of misalignments between safety culture values and the actual safety climate. The study also reveals that the safety perceptions of officers employed directly by ship owners and those by managers do not differ significantly, nor do they differ between senior and junior officers. A shift in perspective towards how seafarers themselves feel towards safety might provide more effective solutions – instead of relying on regulations - and indeed aid in reducing incidents on board. This paper details practical suggestions on how to identify the factors that contribute towards a better safety climate on board ships.

  13. WE-G-BRB-02: The Role of Program Project Grants in Study of 3D Conformal Therapy, Dose Escalation and Motion Management

    Energy Technology Data Exchange (ETDEWEB)

    Fraass, B. [Cedars-Sinai Medical Center (United States)

    2015-06-15

    Over the past 20 years the NIH has funded individual grants, program projects grants, and clinical trials which have been instrumental in advancing patient care. The ways that each grant mechanism lends itself to the different phases of translating research into clinical practice will be described. Major technological innovations, such as IMRT and proton therapy, have been advanced with R01-type and P01-type funding and will be discussed. Similarly, the role of program project grants in identifying and addressing key hypotheses on the potential of 3D conformal therapy, normal tissue-guided dose escalation and motion management will be described. An overview will be provided regarding how these technological innovations have been applied to multi-institutional NIH-sponsored trials. Finally, the panel will discuss regarding which research questions should be funded by the NIH to inspire the next advances in radiation therapy. Learning Objectives: Understand the different funding mechanisms of the NIH Learn about research advances that have led to innovation in delivery Review achievements due to NIH-funded program project grants in radiotherapy over the past 20 years Understand example advances achieved with multi-institutional clinical trials NIH.

  14. Escalation Bias: Does It Extend to Marketing?

    OpenAIRE

    JS Armstrong; Nicole Coviello; Barbara Safranek

    2005-01-01

    Escalation bias implies that managers favor reinvestments in projects that are doing poorly over those doing well. We tested this implication in a marketing context by conducting experiments on advertising and product-design decisions. Each situation was varied to reflect either a long-term or a short-term decision. Besides these four conditions, we conducted three replications. We found little evidence of escalation bias by 365 subjects in the seven experimental comparisons.

  15. Feasibility of PET-CT based hypofractionated accelerated dose escalation in oropharyngeal cancers: Final dosimetric results of the VORTIGERN study. (Secondary endpoint of UK NCRI portfolio: MREC No: 08/H0907/127, UKCRN ID 7341

    Directory of Open Access Journals (Sweden)

    Sanjoy Chatterjee

    2015-01-01

    Conclusion: Hypofractionated, slightly accelerated dose escalation in oropharyngeal cancers is likely to be safe and the chance of trismus is not any higher than when standard dose radiotherapy is used. Active measures to reduce dose to the MA achieves acceptable dose volume parameters even at escalated doses.

  16. Preliminary study on improving safety culture in Malaysian nuclear industries

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Sabariah Kader [KAIST, Daejeon (Korea, Republic of); Lee, Y. E. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2012-10-15

    This paper presents preliminary study on safety culture and its implementation in Malaysian nuclear industries by realizing the importance of safety culture; identification of important safety culture attributes; safety culture assessment and the practices to incorporate the identified safety culture attributes in organization. The first section of this paper explains the terms and definitions related to safety culture. Second, for the realization of importance of safety culture in organization, the international operational experiences emphasizing the importance of safety culture are described. Third, important safety culture attributes which are frequently cited in literature are provided. Fourth, methods to assess safety culture in operating organization are described. Finally, the practices to enhance the safety culture in an organization are discussed.

  17. Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Borghaei, Hossein; Alpaugh, Katherine; Hedlund, Gunnar

    2009-01-01

    recognizing the tumor-associated antigen 5T4. PATIENTS AND METHODS: Patients with non-small-cell lung cancer (NSCLC), pancreatic cancer (PC), and renal cell cancer (RCC) received 5 daily boluses of ABR-217620 (3-month cycles) in escalating doses to determine the maximum-tolerated dose (MTD; ABR-217620 dose...... after therapy. Fourteen patients (36%) had stable disease (SD) on day 56 of the MONO study. Two patients (15%) in the COMBO study had partial responses, one in a patient with progressive disease on prior docetaxel, and five patients (38%) had SD on day 56. CONCLUSION: ABR-217620 was well tolerated....... In the COMBO study, the MTD was 22 microg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration...

  18. E4 - Energy efficient elevators and escalators. Barriers to and strategies for promoting energy-efficient lift and escalator technologies

    Energy Technology Data Exchange (ETDEWEB)

    Duetschke, Elisabeth; Hirzel, Simon

    2010-02-25

    According to prior findings of the E4 project, considerable savings potential exists both for lifts and escalators that could be realized if appropriate technology is implemented. However, energy-efficient technology is slowly diffusing the market - a phenomenon that could be explained by barriers present in the market. A barrier is defined as a mechanism that inhibits a decision or behavior that appears to be both energy-efficient and economically efficient and thereby prevents investment in energy-efficient technologies. This document has two aims. First, it will identify influential barriers in the European lift and escalator market. This analysis is based on the literature as well as a study including interviews as well as group discussions with relevant stakeholders. Second, strategies and measures to overcome the barriers identified in the first step are outlined. Major barriers to the penetration of energy-efficient technologies identified in this paper include a lack of monitoring energy consumption of installations and a lack of awareness of as well as knowledge about energy-efficient technology. Thus, installations and components are usually chosen without a (comprehensive) assessment of their energy consumption and without considering life-cycle approaches. On top of this, split incentives are a regularly occurring barrier. Various stakeholders are influential in the decisionmaking process about an installation or its components. However, those who will later pay for the energy consumption often are not involved in this process. Moreover, it is important to keep in mind that the number of new lifts and escalators installed each year is relatively low compared to the existing stock. Thus, it is very important to discuss enhancement of energy efficiency also for the existing stock. Based on our analyses, several recommendations are developed in this paper that could contribute to a market transformation in the lift and escalator market. First of all, a

  19. A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Christoph Schliemann

    Full Text Available Nintedanib (BIBF 1120, a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily and LDAC (20 mg subcutaneous injection twice daily for 10 days were administered in 28-day cycles. Dose-limiting toxicity (DLT was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62-86] years were enrolled. One patient did not receive study medication and was replaced. Nine (69% patients had relapsed or refractory disease and 6 (46% patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17% with relapsed AML achieved a complete remission (one CR, one CRi and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%. One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41.ClinicalTrials.gov NCT01488344.

  20. A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia.

    Science.gov (United States)

    Schliemann, Christoph; Gerss, Joachim; Wiebe, Stefanie; Mikesch, Jan-Henrik; Knoblauch, Nicola; Sauer, Tim; Angenendt, Linus; Kewitz, Tobias; Urban, Marc; Butterfass-Bahloul, Trude; Edemir, Sabine; Vehring, Kerstin; Müller-Tidow, Carsten; Berdel, Wolfgang E; Krug, Utz

    2016-01-01

    Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62-86] years) were enrolled. One patient did not receive study medication and was replaced. Nine (69%) patients had relapsed or refractory disease and 6 (46%) patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41. ClinicalTrials.gov NCT01488344.

  1. Improving safety culture through the health and safety organization: a case study.

    Science.gov (United States)

    Nielsen, Kent J

    2014-02-01

    International research indicates that internal health and safety organizations (HSO) and health and safety committees (HSC) do not have the intended impact on companies' safety performance. The aim of this case study at an industrial plant was to test whether the HSO can improve company safety culture by creating more and better safety-related interactions both within the HSO and between HSO members and the shop-floor. A quasi-experimental single case study design based on action research with both quantitative and qualitative measures was used. Based on baseline mapping of safety culture and the efficiency of the HSO three developmental processes were started aimed at the HSC, the whole HSO, and the safety representatives, respectively. Results at follow-up indicated a marked improvement in HSO performance, interaction patterns concerning safety, safety culture indicators, and a changed trend in injury rates. These improvements are interpreted as cultural change because an organizational double-loop learning process leading to modification of the basic assumptions could be identified. The study provides evidence that the HSO can improve company safety culture by focusing on safety-related interactions. © 2013. Published by Elsevier Ltd and National Safety Council.

  2. Small Liquid Metal Cooled Reactor Safety Study

    Energy Technology Data Exchange (ETDEWEB)

    Minato, A; Ueda, N; Wade, D; Greenspan, E; Brown, N

    2005-11-02

    The Small Liquid Metal Cooled Reactor Safety Study documents results from activities conducted under Small Liquid Metal Fast Reactor Coordination Program (SLMFR-CP) Agreement, January 2004, between the Central Research Institute of the Electric Power Industry (CRIEPI) of Japan and the Lawrence Livermore National Laboratory (LLNL)[1]. Evaluations were completed on topics that are important to the safety of small sodium cooled and lead alloy cooled reactors. CRIEPI investigated approaches for evaluating postulated severe accidents using the CANIS computer code. The methods being developed are improvements on codes such as SAS 4A used in the US to analyze sodium cooled reactors and they depend on calibration using safety testing of metal fuel that has been completed in the TREAT facility. The 4S and the small lead cooled reactors in the US are being designed to preclude core disruption from all mechanistic scenarios, including selected unprotected transients. However, postulated core disruption is being evaluated to support the risk analysis. Argonne National Laboratory and the University of California Berkeley also supported LLNL with evaluation of cores with small positive void worth and core designs that would limit void worth. Assessments were also completed for lead cooled reactors in the following areas: (1) continuing operations with cladding failure, (2) large bubbles passing through the core and (3) recommendations concerning reflector control. The design approach used in the US emphasizes reducing the reactivity in the control mechanisms with core designs that have essentially no, or a very small, reactivity change over the core life. This leads to some positive void worth in the core that is not considered to be safety problem because of the inability to identify scenarios that would lead to voiding of lead. It is also believed that the void worth will not dominate the severe accident analysis. The approach used by 4S requires negative void worth throughout

  3. Ewing sarcoma localized on spine: a dose escalation study in child; Sarcome d'Ewing localise au rachis: une etude d'escalade de dose chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Vogin, G.; Marchesi, V. [Centre Alexis-Vautrin, Nancy (France); Biston, M.C.; Gassa, F. [Centre Leon-Berard, Lyon (France); Amessis, M.; Zefkili, S.; Helfre, S. [Institut Curie, Paris (France); De Marzi, L.; Lacroix, F.; Leroy, A. [Institut Curie, Orsay (France)

    2011-10-15

    The authors report the study of dose escalation for the treatment of spinal in two types of Ewing tumours. They used 5 dose levels at the rate of five 1,6 Gy per week. They compare different radiotherapy techniques: three-dimensional conformation radiotherapy, static intensity-modulated conformational radiotherapy, helical tomo-therapy, volume-modulated arc-therapy (VMAT), stereotactic radiotherapy, and proton-therapy (in passive diffusion). It appears that it is possible to safely and efficiently deliver until 70,4 Gy in some Ewing tumours. In child, exclusive radiotherapy might become a local treatment option and would require a clinic trial and comparison with exclusive surgery or post-operative radiotherapy. Short communication

  4. DW-MRI and (18) F-FLT PET for early assessment of response to radiation therapy associated with hypoxia-driven interventions. Preclinical studies using manipulation of oxygenation and/or dose escalation.

    Science.gov (United States)

    Tran, Ly-Binh-An; Bol, Anne; Labar, Daniel; Karroum, Oussama; Mignion, Lionel; Bol, Vanesa; Jordan, Bénédicte F; Grégoire, Vincent; Gallez, Bernard

    2016-01-01

    Early markers of treatment response may help in the management of patients by predicting the outcome of a specific therapeutic intervention. Here, we studied the potential value of diffusion-weighted MRI (DW-MRI) and (18)F-fluorothymidine ((18)F-FLT), markers of cell death and cell proliferation respectively, to predict the response to irradiation. In addition, dose escalation and/or carbogen breathing were used to modulate the response to irradiation. The studies were performed on two hypoxic rat tumor models: rhabdomyosarcoma and 9L-glioma. The rats were imaged using MRI and PET before and two days after the treatment. In both tumor models, changes in ADC (apparent diffusion coefficient) and (18)F-FLT SUV (standardized uptake value) were significantly correlated with the tumor growth delay. For both tumor models, the ADC values increased in all irradiated groups two days after the treatment while they decreased in the untreated groups. At the same time, the uptake of (18)F-FLT increased in the untreated groups and decreased in all treated groups. Yet, ADC values were not sensitive enough to predict the added value of dose escalation or carbogen breathing in either model. Change in (18)F-FLT uptake was able to predict the higher tumor response when using increased dose of irradiation, but not when using a carbogen breathing challenge. Our results also emphasize that the magnitude of change in (18)F-FLT uptake was strongly dependent on the tumor model. Copyright © 2015 John Wiley & Sons, Ltd.

  5. The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study

    Directory of Open Access Journals (Sweden)

    Jones R

    2017-08-01

    Full Text Available Rupert Jones,1 Jessica Martin,2 Vicky Thomas,3 Derek Skinner,4 Jonathan Marshall,5 Martina Stagno d’Alcontres,2 David Price2,6 1Clinical Trials and Health Research, Institute of Translational and Stratified Medicine, Plymouth University Peninsula School of Medicine and Dentistry, Plymouth, UK; 2Observational and Pragmatic Research Institute, Singapore; 3Cambridge Research Support, Cambridge, UK; 4Optimum Patient Care, Cambridge, UK; 5Mundipharma International Limited, Cambridge, UK; 6Centre for Academic Primary Care, University of Aberdeen, Aberdeen, UK Abstract: Chronic obstructive pulmonary disease (COPD, a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs and dry powder inhalers (DPIs show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA prescriptions, for COPD patients initiating fluticasone propionate (FP/salmeterol xinafoate (SAL via pMDI versus DPI at two doses of FP (500 and 1,000 µg/d using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 µg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%] versus DPI (115 [49

  6. Early warning scores: unravelling detection and escalation.

    Science.gov (United States)

    Smith, Gary B; Prytherch, David R; Meredith, Paul; Schmidt, Paul E

    2015-01-01

    The purpose of this paper is to increase understanding of how patient deterioration is detected and how clinical care escalates when early warning score (EWS) systems are used. The authors critically review a recent National Early Warning Score paper published in IJHCQA using personal experience and EWS-related publications, and debate the difference between detection and escalation. Incorrect EWS choice or poorly understood EWS escalation may result in unnecessary workloads forward and responding staff. EWS system implementers may need to revisit their guidance materials; medical and nurse educators may need to expand the curriculum to improve EWS system understanding and use. The paper raises the EWS debate and alerts EWS users that scrutiny is required.

  7. Escalation scenarios initiated by gas explosions on offshore installations. Probabilistic cause and consequence modelling

    Energy Technology Data Exchange (ETDEWEB)

    Eknes, Monika Loeland

    1996-12-31

    This Dr. ing. thesis deals with escalation scenarios initiated by gas explosions on offshore installations. Gas explosions is one of the major hazards to such installations. The objectives were to estimate the probability of ignition and frequency of gas explosions for gas leaks on top sides of offshore installations, and to estimate the response and resistance of components that could result in escalation if they failed. Main fields considered cover risk analysis methodology, gas explosions, simplified escalation models, evaluation of structural consequences, case studies, and guidelines. 107 refs., 33 figs., 33 tabs.

  8. Oral ganciclovir in children : Pharmacokinetics, safety, tolerance, and antiviral effects

    NARCIS (Netherlands)

    Frenkel, LM; Capparelli, EV; Dankner, WM; Smith, IL; Ballow, A; Culnane, M; Read, JS; Thompson, M; Mohan, KM; Shaver, A; Robinson, CA; Stempien, MJ; Burchett, SK; Melvin, AJ; Borkowsky, W; Petru, A; Kovacs, A; Yogev, R; Goldsmith, J; McFarland, EJ; Spector, SA

    2000-01-01

    The pharmacokinetics, safety, tolerance, and antiviral effects of ganciclovir (Gcv) administered orally were evaluated in 36 children infected with cytomegalovirus (CMV) who were severely immunocompromised by infection with human immunodeficiency virus type 1, In this dose-escalation study, 30 mg/kg

  9. Teaching microbiological food safety through case studies

    Directory of Open Access Journals (Sweden)

    Florence Dubois-Brissonnet

    2015-10-01

    Full Text Available Higher education students usually ask for more training based on case studies. This was addressed by designing a specific food safety module (24 hours in which students were shown how to predict microbiological risks in food products i.e. they were asked to determine product shelf-life according to product formulation, preservation methods and consumption habits using predictive microbiology tools. Working groups of four students first identified the main microbiological hazards associated with a specific product. To perform this task, they were given several documents including guides for good hygiene practices, reviews on microbiological hazards in the food sector, flow sheets, etc…  After three-hours of work, the working groups prepared and gave an oral presentation in front of their classmates and professors. This raised comments and discussion that allowed students to adjust their conclusions before beginning the next step of their work. This second step consisted in the evaluation of the safety risk associated with the two major microbiological hazards of the product studied, using predictive microbiology. Students then attended a general lecture on the different tools of predictive microbiology and tutorials (6 hours that made them familiar with the modelling of bacterial growth or inactivation. They applied these tools (9 hours to predict the shelf-life of the studied product according to various scenarios of preservation (refrigeration, water activity, concentration of salt or acid, modified atmosphere, etc… and/or consumption procedures (cooking. The module was concluded by oral presentations of each working group and included student evaluation (3 hours.

  10. Lessons learned from measuring safety culture: an Australian case study.

    Science.gov (United States)

    Allen, Suellen; Chiarella, Mary; Homer, Caroline S E

    2010-10-01

    adverse events in maternity care are relatively common but often avoidable. International patient safety strategies advocate measuring safety culture as a strategy to improve patient safety. Evidence suggests it is necessary to fully understand the safety culture of an organisation to make improvements to patient safety. this paper reports a case study examining the safety culture in one maternity service in Australia and considers the benefits of using surveys and interviews to understand safety culture as an approach to identify possible strategies to improve patient safety in this setting. the study took place in one maternity service in two public hospitals in NSW, Australia. Concurrently, both hospitals were undergoing an organisational restructure which was part of a major health reform agenda. The priorities of the reform included improving the quality of care and patient safety; and, creating a more efficient health system by reducing administration inefficiencies and duplication. a descriptive case study using three approaches: the safety culture was identified to warrant improvement across all six safety culture domains. There was reduced infrastructure and capacity to support incident management activities required to improve safety, which was influenced by instability from the organisational restructure. There was a perceived lack of leadership at all levels to drive safety and quality and improving the safety culture was neither a key priority nor was it valued by the organisation. the safety culture was complex as was undertaking this study. We were unable to achieve a desired 60% response rate highlighting the limitations of using safety culture surveys in isolation as a strategy to improve safety culture. Qualitative interviews provided greater insight into the factors influencing the safety culture. The findings of this study provide evidence of the benefits of including qualitative methods with quantitative surveys when examining safety culture

  11. Improving patient safety culture in general practice: an interview study

    NARCIS (Netherlands)

    Verbakel, N.J.; de Bont, A.A.; Verheij, T.J.M.; Wagner, C.; Zwart, D.L.M.

    2015-01-01

    Background When improving patient safety a positive safety culture is key. As little is known about improving patient safety culture in primary care, this study examined whether administering a culture questionnaire with or without a complementary workshop could be used as an intervention for

  12. Improving patient safety culture in general practice: An interview study

    NARCIS (Netherlands)

    N.J. Verbakel (Natasha J.); A.A. de Bont (Antoinette); T.J. Verheij; C. Wagner (Cordula); D.L.M. Zwart (Dorien)

    2015-01-01

    textabstractBackground When improving patient safety a positive safety culture is key. As little is known about improving patient safety culture in primary care, this study examined whether administering a culture questionnaire with or without a complementary workshop could be used as an

  13. Elephant invasion and escalated depletion of environmental ...

    African Journals Online (AJOL)

    For decades, elephants' invasion is known to be associated with severe environmental consequences leading to escalated depletion o environmental resources (plants, water, wildlife and soil). This paper examined the effects of elephants' activity on the environmental resources inHong and Gombi Local Government areas ...

  14. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial.

    Science.gov (United States)

    Sibbing, Dirk; Aradi, Dániel; Jacobshagen, Claudius; Gross, Lisa; Trenk, Dietmar; Geisler, Tobias; Orban, Martin; Hadamitzky, Martin; Merkely, Béla; Kiss, Róbert Gábor; Komócsi, András; Dézsi, Csaba A; Holdt, Lesca; Felix, Stephan B; Parma, Radoslaw; Klopotowski, Mariusz; Schwinger, Robert H G; Rieber, Johannes; Huber, Kurt; Neumann, Franz-Josef; Koltowski, Lukasz; Mehilli, Julinda; Huczek, Zenon; Massberg, Steffen

    2017-10-14

    Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Between Dec 2, 2013, and May 20, 2016, 2610 patients were

  15. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial.

    Science.gov (United States)

    Fizazi, Karim; Massard, Christophe; Bono, Petri; Jones, Robert; Kataja, Vesa; James, Nicholas; Garcia, Jorge A; Protheroe, Andrew; Tammela, Teuvo L; Elliott, Tony; Mattila, Leena; Aspegren, John; Vuorela, Annamari; Langmuir, Peter; Mustonen, Mika

    2014-08-01

    ODM-201 is a novel androgen receptor (AR) inhibitor designed to block the growth of prostate cancer cells through high-affinity binding to the AR and inhibition of AR nuclear translocation. This trial assessed ODM-201's safety, pharmacokinetics, and activity in men with metastatic castration-resistant prostate cancer. The ARADES trial is an open-label phase 1-2 trial undertaken in 23 hospitals across Europe and USA with ongoing long-term follow-up. Men with progressive metastatic castration-resistant prostate cancer, who had castrate concentrations of testosterone and an Eastern Cooperative Oncology Group score of 0-1 were enrolled. In the phase 1 part of the trial, patients were given oral ODM-201 at a starting daily dose of 200 mg, which was increased to 400 mg, 600 mg, 1000 mg, 1400 mg, and 1800 mg. In phase 2, patients were randomly assigned centrally and stratified by previous chemotherapy and treatment with CPY17 inhibitors, to receive one of three daily doses of ODM-201 (200 mg, 400 mg, and 1400 mg). The primary endpoint in phase 1 was safety and tolerability, whereas in phase 2 it was the proportion of patients with a PSA response (50% or greater decrease in serum PSA) at week 12. All analyses included patients who had received at least one dose of ODM-201. This trial is registered with ClinicalTrials.gov, number NCT01317641, and NCT01429064 for the follow-up after 12 weeks. We enrolled patients between April 5, 2011, and March 12, 2013. In phase 1, 24 patients were enrolled to six sequential cohorts of three to six patients and received a daily dose of ODM-201, 200-1800 mg. No dose-limiting toxic effects were reported and the maximum tolerated dose was not reached. In phase 1, three patients reported eight adverse events of grade 3 (fracture, muscle injury, laceration, paralytic ileus, pain, presyncope, urinary retention, and vomiting) and one patient had a grade 4 adverse event (lymphoedema). None of the grade 3-4 adverse events were deemed to be related

  16. Migration, Occupational Mobility, and Regional Escalators in Scotland

    Directory of Open Access Journals (Sweden)

    Maarten van Ham

    2012-01-01

    Full Text Available This paper seeks to unpick the complex relationship between an individual’s migration behaviour, their place of residence, and their occupational performance in the Scottish labour market between 1991 and 2001. We investigate whether Edinburgh has emerged as an occupational escalator region and whether individuals moving there experience more rapid upward occupational mobility than those living and moving elsewhere. Using country of birth, we also control for an individual’s propensity to make long distance moves during earlier periods of their life course. Using data from the Scottish Longitudinal Study, linking 1991 and 2001 individual census records, and logistic regressions, we show that those who migrate over long distances within or to Scotland are most likely to achieve upward occupational mobility. We also found that Edinburgh is by far the most important regional escalator in Scotland; those moving to Edinburgh are the most likely to experience upward occupational mobility from low to high occupational status jobs. This is an important finding as most of the literature on escalator regions focuses on international mega cities.

  17. The effects of mortality salience on escalation of commitment.

    Science.gov (United States)

    Yen, Chih-Long; Lin, Chun-Yu

    2012-01-01

    Based on propositions derived from terror management theory (TMT), the current study proposes that people who are reminded of their mortality exhibit a higher degree of self-justification behavior to maintain their self-esteem. For this reason, they could be expected to stick with their previous decisions and invest an increasing amount of resources in those decisions, despite the fact that negative feedback has clearly indicated that they might be on a course toward failure (i.e., "escalation of commitment"). Our experiment showed that people who were reminded of their mortality were more likely to escalate their level of commitment by maintaining their current course of action. Two imaginary scenarios were tested. One of the scenarios involved deciding whether to send additional troops into the battlefield when previous attempts had failed; the other involved deciding whether to continue developing an anti-radar fighter plane when the enemy had already developed a device to detect it. The results supported our hypothesis that mortality salience increases the tendency to escalate one's level of commitment.

  18. Fusion safety studies in Russia in 2003

    Energy Technology Data Exchange (ETDEWEB)

    Kolbasov, B.N. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation)]. E-mail: kolbasov@nfi.kiae.ru; Guseva, M.I. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Khripunov, B.I. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Martynenko, Yu.V. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Zimin, A.M. [N.E. Bauman Moscow State Technical University, 2nd Bauman ul. 5, 107005 Moscow (Russian Federation); Stankevich, V.G. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Svechnikov, N.Yu. [Russian Research Center ' Kurchatov Institute' , Pl. Kurchatova 1, 123182 Moscow (Russian Federation); Bartenev, S.A. [V.G. Khlopin Radium Institute, 2nd Murinskij Prospect 28, 194021 St.-Petersburg (Russian Federation)

    2005-11-15

    The paper presents a review of the fusion safety studies performed in Russia in 2003. Among the findings is the effect of tungsten sputtering by subthreshold energy ions at high temperature, which tends to decrease with irradiation dose. The size distribution of W-erosion products (spherical droplets or flakes) depends on the positioning of the collector. Studies of Be + D(H) films revealed that D/Be ratio in co-deposited Be-D films decreases from 0.15 at 375 K to 0.05 at 575 K. Hydrogen concentration in Be + C films, exposed to acetylene ion flux at 670 K, decreased from 20-24 to 6 at.% with increase in irradiation dose from 10{sup 23} to 10{sup 24} m{sup -2}. The analysis of spectroscopic characteristics of C-D films deposited inside the T-10 tokamak vacuum chamber provides qualitative insight into the physical and chemical reasons behind the preferential retention of the heavier hydrogen isotope in the tokamak erosion films. An extraction scheme for radiochemical reprocessing of activated V-Cr-Ti alloy after a fusion reactor decommissioning was developed and checked experimentally. It takes 48 extraction steps to recover V, Cr and Ti down to an effective dose rate <12.5 {mu}Sv/h, permitting the refabrication of these metals without any biological shielding from ionizing radiation.

  19. Safety studies on Korean fusion DEMO plant using Integrated Safety Assessment Methodology: Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Kyemin; Kang, Myoung-suk [Kyung Hee University, Yongin-si, Gyeonggi-do 446-701 (Korea, Republic of); Heo, Gyunyoung, E-mail: gheo@khu.ac.kr [Kyung Hee University, Yongin-si, Gyeonggi-do 446-701 (Korea, Republic of); Kim, Hyoung-chan [National Fusion Research Institute, Daejeon-si 305-333 (Korea, Republic of)

    2015-10-15

    Highlights: • The purpose of this paper is to suggest methodology that can investigate safety issues and provides a case study for Korean fusion DEMO plant. • The concepts of Integrated Safety Assessment Methodology (ISAM) that can be applied in addressing regulatory requirements and recognizing safety issues for K-DEMO were emphasized. • Phenomena Identification Ranking Table (PIRT) and Objective Provision Tree (OPT) were performed and updated. • This work is expected to contribute on the conceptual design of safety features for K-DEMO to design engineers and the guidance for regulatory requirements to licensers. - Abstract: The purpose of this paper is to investigate safety issues using Integrated Safety Assessment Methodology (ISAM) proposed by Generation IV Forum Risk and Safety Working Group (RSWG) for Korean fusion DEMO plant (K-DEMO). In ongoing nuclear energy research such as Generation IV fission power plant (GEN-IV), new methodology based on Technology-Neutral Framework (TNF) has been applied for safety assessment. In this methodology, design and regulatory requirements for safety of nuclear power plants are considered simultaneously. The design based on regulatory requirements can save resource, time, and manpower while maintaining high level safety. ISAM is one of the options to apply TNF in K-DEMO. We have performed safety studies for K-DEMO using Phenomena Identification and Ranking Table (PIRT) and Objective Provision Tree (OPT) which are constitutive part of ISAM. Considering the design phase of K-DEMO, the current study focused on PIRT and OPT for K-DEMO. Results have been reviewed and updated by Korean fusion advisory group after considering the views of specialists from domestic universities, industries, and national institutes in South Korea.

  20. Is attention deficit/hyperactivity disorder among men associated with initiation or escalation of substance use at 15‐month follow‐up? A longitudinal study involving young Swiss men

    Science.gov (United States)

    Vogel, Tanja; Dom, Geert; van de Glind, Geurt; Studer, Joseph; Gmel, Gerhard; Strik, Werner

    2016-01-01

    Abstract Background and Aims Young adults with attention deficit/hyperactivity disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non‐ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of substance use at 15‐month follow‐up in men screened positive or negative for ADHD (ADHD+ versus ADHD–), controlling for CD presence in early adolescence. Design Participants were recruited during August 2010 and November 2011 from the census of all young men who have to pass mandatory army conscription from three of six Swiss Army recruitment centres. A two‐wave data collection was performed via questionnaires at baseline and 15‐month follow‐up as a part of the longitudinal Cohort Study on Substance Use Risk Factors. Setting Recruitment centres in Lausanne, Windisch and Mels, responsible for 21 cantons in German‐ and French‐speaking areas of Switzerland. Participants Consecutive sample of 5103 male Swiss Army conscripts who provided informed consent and responded to questionnaires at baseline and 15‐month follow‐up. Their mean age was 20.0 (standard deviation = 1.21) years at baseline. Measurements ADHD and CD were assessed using the adult ADHD Self‐Report Scale and the MINI International Neuropsychiatric Interview Plus, respectively, at baseline, and substance use was measured via self‐administered substance use questionnaires at baseline and follow‐up. Findings Compared with the ADHD– group, the ADHD+ group (n = 215, 4.2%) showed heavier baseline substance use and increased likelihood of alcohol (χ2 = 53.96; P ADHD+ group was more likely to initiate substance use compared with the ADHD– group (higher initiation rates), particularly with amphetamines [odds ratio (OR) = 3.81; 95% confidence interval (CI) = 2.20–6.60; P ADHD medication (OR = 4.45; 95% CI = 2.06–9.60; P

  1. The probabilistic studies of safety; Les etudes probabilistes de surete

    Energy Technology Data Exchange (ETDEWEB)

    Lacoste, A.C. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Kalalo, E.; Brenot, D. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Pichereau, F.; Lanore, J.M.; Corenwinder, F.; Dupuy, P.; Corenwinder, F. [Institut de Radioprotection et de Surete Nucleaire (IRSN), 92 - Clamart (France); Primet, J.; Huyart, Th.; Faidy, C.; Meister, E.; Ardillon, E.; Le Bot, P. [Electricite de France (EDF), 75 - Paris (France); Maurin, Th. [Direction Gle de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France); Gryffroy, D. [Association Vincotte Nucleaire (Belgium); Sandberg, J.; Virolainen, R. [STUK, Helsinki (Finland); Merrifield, J.S. [Nuclear Regulatory Commission (United States); Hill, T. [National Nuclear Regulator, Cape Town (South Africa); Cahen, B. [Ministere de Ecologie et du Developpement Durable, 75 - Paris (France); Chevalier, B. [Shell France, 92 - Colombes (France)

    2003-11-15

    The safety of the French nuclear reactors is based on determinist studies. The probabilistic studies of safety allow to complete the classical determinist analysis with a particular method of investigation. The probabilistic studies of safety are an evaluation method of risks based on a systematic investigation of accidental scenarios. They are composed of a whole of technical analysis allowing to estimate the risks linked to nuclear installations in term of frequency of accidental events and their consequences. (N.C.)

  2. Organic Tanks Safety Program: Waste aging studies

    Energy Technology Data Exchange (ETDEWEB)

    Camaioni, D.M.; Samuels, W.D.; Lenihan, B.D.; Clauss, S.A.; Wahl, K.L.; Campbell, J.A.

    1994-11-01

    The underground storage tanks at the Hanford Complex contain wastes generated from many years of plutonium production and recovery processes, and mixed wastes from radiological degradation processes. The chemical changes of the organic materials used in the extraction processes have a direct on several specific safety issues, including potential energy releases from these tanks. This report details the first year`s findings of a study charged with determining how thermal and radiological processes may change the composition of organic compounds disposed to the tank. Their approach relies on literature precedent, experiments with simulated waste, and studies of model reactions. During the past year, efforts have focused on the global reaction kinetics of a simulated waste exposed to {gamma} radiation, the reactions of organic radicals with nitrite ion, and the decomposition reactions of nitro compounds. In experiments with an organic tank non-radioactive simulant, the authors found that gas production is predominantly radiolytically induced. Concurrent with gas generation they observe the disappearance of EDTA, TBP, DBP and hexone. In the absence of radiolysis, the TBP readily saponifies in the basic medium, but decomposition of the other compounds required radiolysis. Key organic intermediates in the model are C-N bonded compounds such as oximes. As discussed in the report, oximes and nitro compounds decompose in strong base to yield aldehydes, ketones and carboxylic acids (from nitriles). Certain aldehydes can react in the absence of radiolysis to form H{sub 2}. Thus, if the pathways are correct, then organic compounds reacting via these pathways are oxidizing to lower energy content. 75 refs.

  3. A randomized, double-blind, multiple-dose escalation study of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) for moderate to severe menopausal symptoms and quality of life in postmenopausal women.

    Science.gov (United States)

    Wang, Chi Chiu; Cheng, King Fai; Lo, Wing Man; Law, Cindy; Li, Lu; Leung, Ping Chung; Chung, Tony Kwok Hung; Haines, Christopher John

    2013-02-01

    This study is a phase II clinical trial that aims to investigate the dose-response relationship of a Chinese herbal medicine preparation, Dang Gui Buxue Tang (DBT), with short-term menopausal symptoms and quality of life in local postmenopausal women. A randomized, double-blind, multiple-dose escalation trial was performed in 60 postmenopausal women experiencing severe hot flashes and night sweats. The participants were randomized to receive DBT preparations at 1.5, 3.0, or 6.0 g/day for 12 weeks. The primary outcomes were vasomotor symptoms, Greene Climacteric Scale (GCS) score, and Menopause-Specific Quality of Life (MENQOL) score. Secondary outcomes included serum hormones and lipids. There were between-group differences in psychological/psychosocial (P = 0.015, GCS; P = 0.013, MENQOL) and somatic/physical (P = 0.019, GCS; P = 0.037, MENQOL) domains, and improvement was significantly greatest (P DBT preparations at 6.0 g/day significantly improve physical and psychological scores and significantly reduce vasomotor symptoms from baseline. The treatment was well tolerated, with no serious adverse events noted during the 12-week intervention period. The changes do not affect hormones and lipid profiles.

  4. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  5. Combustion Safety Simplified Test Protocol Field Study

    Energy Technology Data Exchange (ETDEWEB)

    Brand, L [Gas Technology Inst., Des Plaines, IL (United States); Cautley, D. [Gas Technology Inst., Des Plaines, IL (United States); Bohac, D. [Gas Technology Inst., Des Plaines, IL (United States); Francisco, P. [Gas Technology Inst., Des Plaines, IL (United States); Shen, L. [Gas Technology Inst., Des Plaines, IL (United States); Gloss, S. [Gas Technology Inst., Des Plaines, IL (United States)

    2015-11-05

    "9Combustions safety is an important step in the process of upgrading homes for energy efficiency. There are several approaches used by field practitioners, but researchers have indicated that the test procedures in use are complex to implement and provide too many false positives. Field failures often mean that the house is not upgraded until after remediation or not at all, if not include in the program. In this report the PARR and NorthernSTAR DOE Building America Teams provide a simplified test procedure that is easier to implement and should produce fewer false positives. A survey of state weatherization agencies on combustion safety issues, details of a field data collection instrumentation package, summary of data collected over seven months, data analysis and results are included. The project provides several key results. State weatherization agencies do not generally track combustion safety failures, the data from those that do suggest that there is little actual evidence that combustion safety failures due to spillage from non-dryer exhaust are common and that only a very small number of homes are subject to the failures. The project team collected field data on 11 houses in 2015. Of these homes, two houses that demonstrated prolonged and excessive spillage were also the only two with venting systems out of compliance with the National Fuel Gas Code. The remaining homes experienced spillage that only occasionally extended beyond the first minute of operation. Combustion zone depressurization, outdoor temperature, and operation of individual fans all provide statistically significant predictors of spillage.

  6. From Crisis to De-escalation: An Examination of Politics in a U.S. High School Steroid Testing Program.

    Science.gov (United States)

    Berg, Brennan K; Winsley, Kathryn; Fuller, Rhema D; Hutchinson, Michael

    2017-01-01

    Preventing the use of performance enhancing drugs in sport has long been a concern for policymakers. In the United States, amidst national attention the state of Texas constructed the country's largest steroid testing program for high school athletes. However, resource allocation steadily declined until the program was defunded in 2015. Using escalation of commitment theory as a framework, this conceptual paper examines the critical, but less studied, role of politics and de-escalation behavior that directed this distinct sport situation. By combining policy and media documents with the academic literature, this paper allows for a greater understanding of how the steroid testing program was formulated and implemented, which may influence how policymakers address steroids among amateur athletes in the future. This paper also offers new opportunities for future research by highlighting a new sport context in which escalation of commitment theory applies and specifically noting the significant role politics can play in escalation or de-escalation decision making.

  7. Environmental Regulation and Food Safety: Studies of Protection ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Environmental Regulation and Food Safety: Studies of Protection and Protectionism. Book cover Environmental Regulation and Food Safety: Studies of Protection and Protectionism. Directeur(s) : Veena Jha. Maison(s) d'édition : Edward Elgar, IDRC. 1 janvier 2006. ISBN : 184542512X. 250 pages. e-ISBN : 155250185X.

  8. A randomised dose escalation study of subcutaneous interleukin 2 with and without levamisole in patients with metastatic renal cell carcinoma or malignant melanoma.

    OpenAIRE

    Ahmed, F Y; Leonard, G A; A'Hern, R.; Taylor, A. E.; Lorentzos, A.; Atkinson, H; Moore, J.; Nicolson, M. C.; Riches, P G; Gore, M E

    1996-01-01

    We have examined the efficacy, toxicity and host immunological response of two different dose schedules of interleukin 2 (IL-2) given subcutaneously, daily for 3 months in patients with renal cell carcinoma (RCC) or metastatic melanoma (MM). We also examined the effect of adding the immune modulator levamisole to the two different schedules of IL-2. Thirty-nine patients were entered into two sequential phase I/II studies. Eighteen patients entered study 1 and were randomised to receive IL-2, ...

  9. Dose Escalation and Healthcare Resource Use among Ulcerative Colitis Patients Treated with Adalimumab in English Hospitals: An Analysis of Real-World Data.

    Directory of Open Access Journals (Sweden)

    Christopher M Black

    Full Text Available To describe the real-world use of adalimumab for maintenance treatment of ulcerative colitis (UC and associated healthcare costs in English hospitals.Retrospective cohort study.Analysis of NHS Hospital Episode Statistics linked with pharmacy dispensing data in English hospitals.Adult UC patients receiving ≥240mg during adalimumab treatment induction, subsequently maintained on adalimumab.Frequency and pattern of adalimumab use and dose escalation during maintenance treatment and associated healthcare costs (prescriptions and hospital visits.191 UC patients completed adalimumab treatment induction. 83 (43.46% dose escalated during maintenance treatment by ≥100% (equivalent to weekly dosing (median time to dose escalation: 139 days. 56 patients (67.47% subsequently de-escalated by ≥50% (median time to dose de-escalation: 21 days. Mean all-cause healthcare costs for all patients ≤12 months of index were £13,892. Dose escalators incurred greater mean healthcare costs than non-escalators ≤12 months of index (£14,596 vs. £13,351. Prescriptions accounted for 96.49% of UC-related healthcare costs (£11,090 of £11,494 in all patients.Within the cohort, 43.46% of UC patients escalated their adalimumab dose by ≥100% and incurred greater costs than non-escalators. The apparent underestimation of adalimumab dose escalation in previous studies may have resulted in underestimated costs in healthcare systems.

  10. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik V; Jensen, Lars Henrik; Sorensen, Morten

    2011-01-01

    Abstract Introduction. Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin...

  11. A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Jensen, Lars Henrik; Sorensen, Morten

    2011-01-01

    Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C...

  12. Nonresponders to Daily Paroxetine and Another SSRI in Men With Lifelong Premature Ejaculation : A Pharmacokinetic Dose-Escalation Study for a Rare Phenomenon

    NARCIS (Netherlands)

    Janssen, Paddy Kc; Touw, Daan; Schweitzer, Dave H; Waldinger, Marcel D

    PURPOSE: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. MATERIALS

  13. Nonresponders to daily paroxetine and another SSRI in men with lifelong premature ejaculation : a pharmacokinetic dose-escalation study for a rare phenomenon

    NARCIS (Netherlands)

    Janssen, Paddy Kc; Touw, Daan; Schweitzer, Dave H; Waldinger, Marcel D

    PURPOSE: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. MATERIALS

  14. Combustion Safety Simplified Test Protocol Field Study

    Energy Technology Data Exchange (ETDEWEB)

    Brand, L. [Gas Technology Inst., Des Plaines, IL (United States); Cautley, D. [Gas Technology Inst., Des Plaines, IL (United States); Bohac, D. [Gas Technology Inst., Des Plaines, IL (United States); Francisco, P. [Gas Technology Inst., Des Plaines, IL (United States); Shen, L. [Gas Technology Inst., Des Plaines, IL (United States); Gloss, S. [Gas Technology Inst., Des Plaines, IL (United States)

    2015-11-01

    Combustions safety is an important step in the process of upgrading homes for energy efficiency. There are several approaches used by field practitioners, but researchers have indicated that the test procedures in use are complex to implement and provide too many false positives. Field failures often mean that the house is not upgraded until after remediation or not at all, if not include in the program. In this report the PARR and NorthernSTAR DOE Building America Teams provide a simplified test procedure that is easier to implement and should produce fewer false positives. A survey of state weatherization agencies on combustion safety issues, details of a field data collection instrumentation package, summary of data collected over seven months, data analysis and results are included. The project team collected field data on 11 houses in 2015.

  15. Exploring Safety Culture in Jordanian Hospitals: A Baseline Study.

    Science.gov (United States)

    Suliman, Mohammad; Aljezawi, Maen; AlBashtawy, Mohammed; Fitzpatrick, Joyce; Aloush, Sami; Al-Awamreh, Khitam

    Medical error is a serious issue in hospitals in Jordan. This study explored Jordanian nurses' perceptions of the culture of safety in their hospitals. The Hospital Survey of Patient Safety Culture translated into Arabic was administered to a convenience sample of 391 nurses from 7 hospitals in Jordan. The positive responses to the 12 dimensions of safety culture ranged from 20.0% to 74.6%. These are lower than the benchmarks of the Agency for Healthcare Research and Quality. Jordanian nurses perceive their hospitals as places that need more effort to improve the safety culture.

  16. Phase I, Dose-Escalation Study of the Targeted Cytotoxic LHRH Analog AEZS-108 in Patients with Castration- and Taxane-Resistant Prostate Cancer

    OpenAIRE

    Liu, Stephen V.; Tsao-Wei, Denice D.; Xiong, Shigann; Groshen, Susan; Dorff, Tanya B.; Quinn, David I.; Tai, Yu-Chong; Engel, Juergen; Hawes, Debra; Schally, Andrew V.; Pinski, Jacek K.

    2014-01-01

    Background: AEZS-108, formerly AN-152, is a cytotoxic hybrid molecule consisting of an LHRH agonist moiety covalently coupled to doxorubicin, allowing it to deliver doxorubicin selectively to cells expressing LHRH receptors. LHRH receptors are expressed on the cell membrane of many tumors, including prostate cancer (PC). This Phase I study determined the maximum tolerated dose (MTD) of AEZS-108 in men with taxane- and castration-resistant PC (CRPC) while providing additional information on th...

  17. Safety and efficacy of desmopressin for the treatment of nocturia in elderly patients: a cohort study.

    Science.gov (United States)

    Song, Miho; Hong, Bum Sik; Chun, Ji-Youn; Han, Ji-Yeon; Choo, Myung-Soo

    2014-08-01

    Desmopressin is used widely to treat nocturnal polyuria (NP), but there is concern of hyponatremia especially in elderly patients. This study aimed to evaluate the safety and efficacy of long-term desmopressin treatment in elderly patients with NP. Patients who were ≥65 years old with NP were analyzed. All patients were started on 0.1 mg desmopressin, and the dose was escalated to 0.2 mg depending on patient symptoms. All patients were educated the mechanism of desmopressin. The voiding diary and serum sodium levels were evaluated at baseline, 3-7 days after starting treatment and every 3-6 months. Safety was evaluated by hyponatremia, hyponatremic symptoms and other adverse drug events. The mean changes in number of nocturia and nocturnal urine volume (NUV) were evaluated for efficacy. A total of 68 patients were included. The mean age was 72.6 (66-85) years. The mean night-time frequency was 3.0 ± 1.8 day, and the mean serum sodium level was 141.2 ± 2.1 mEq/L at baseline. The mean follow-up period was 27.9 months. The mean decrease in serum sodium level was 1.3 ± 3.4 mEq/L at the last follow-up (p = 0.003). Hyponatremia incidence was 4.4 %, and all patients recovered by stopping medication. Severe adverse events were not observed. The mean night-time frequency had decreased by 2.1, and the NUV had decreased by 374.2 ± 261.3 mL at the last follow-up (p Desmopressin at doses below 0.2 mg is safe and effective in elderly patients with NP if patients are well informed and are closely followed up.

  18. Nonresponders to daily paroxetine and another SSRI in men with lifelong premature ejaculation: a pharmacokinetic dose-escalation study for a rare phenomenon.

    Science.gov (United States)

    Janssen, Paddy Kc; Touw, Daan; Schweitzer, Dave H; Waldinger, Marcel D

    2014-09-01

    Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. Five males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations. Between the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three treatment periods nor between leptin

  19. Age and Workers' Perceptions of Workplace Safety: A Comparative Study

    Science.gov (United States)

    Gyekye, Seth Ayim; Salminen, Simo

    2009-01-01

    The study examined the relationship between age and I) safety perception; ii) job satisfaction; iii) compliance with safety management policies; and (iv) accident frequency. Participants were Ghanaian industrial workers (N = 320) categorized into 4 age groups: 19-29 years; 30-39 years; 40-50 years; and 51 years and above. Workplace safety…

  20. Escalation of daunorubicin and addition of etoposide in the ADE regimen in acute myeloid leukemia patients aged 60 years and older: Cancer and Leukemia Group B Study 9720.

    Science.gov (United States)

    Baer, M R; George, S L; Sanford, B L; Mrózek, K; Kolitz, J E; Moore, J O; Stone, R M; Powell, B L; Caligiuri, M A; Bloomfield, C D; Larson, R A

    2011-05-01

    Untreated de novo (n=421) and secondary (n=189) acute myeloid leukemia (AML) patients ≥60 years received intensified chemotherapy, including daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) during days 1, 2, 3 with cytarabine 100 mg/m(2) during days 1-7, with a second induction if needed and one consolidation course with these drugs and doses for 2, 2 and 5 days, respectively. In all, 287 (47%) achieved complete remission (CR), 136 (22%) died and 187 (31%) were non-responders. CR rates were 27, 44 and 52% for complex karyotypes, rare aberrations and neither (P<0.001), 52 and 37% for de novo and secondary AML (P=0.003), and 53 and 42% for age 60-69 and ≥70 years (P=0.015). In multivariable analysis, CR predictors included non-complex/non-rare karyotypes (P<0.001), de novo AML (P<0.001), better performance status (PS) (P<0.001) and younger age (P=0.001). Disease-free (DFS) and overall (OS) survival medians were 6.8 (95% CI: 6.2, 7.8) and 7.2 (95% CI: 6.4, 8.6) months. In multivariable analysis, DFS was shorter for complex karyotypes (P<0.001) and increasing white blood count (WBC) (P<0.001) and age (P=0.038), and OS for complex karyotypes (P<0.001), increasing WBC (P=0.001) and age (P<0.001), poorer PS (P<0.001) and secondary AML (P=0.010). Outcomes and prognostic factors were similar to those in previous Cancer and Leukemia Group B studies.

  1. Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies

    Science.gov (United States)

    Puzanov, Igor; LoRusso, Patricia M.; Cohen, Roger B.; Morris, John C.; Olowokure, Olugbenga O.; Yin, Jian Y.; Doroumian, Séverine; Shen, Liji; Olszanski, Anthony J.

    2015-01-01

    Taxane–gemcitabine combinations have demonstrated antitumor activity. This phase I study (NCT01001221) aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus gemcitabine and to assess the preliminary efficacy of this combination. The patients included had metastatic or unresectable solid tumors and had exhausted standard treatment. Cohorts of three to six patients received cabazitaxel (15–20 mg/m2) before (part 1a) or after (part 1b) gemcitabine (700–1000 mg/m2) on Day 1 and gemcitabine alone on Day 8. Prophylactic growth factors were not allowed in cycle 1. In part 1a (n=12), five patients received 20 mg/m2 cabazitaxel plus 1000 mg/m2 gemcitabine (20/1000), five received 15/900, two received 15/700. In part 1b, all six patients received the lowest dose (700/15). At all doses, two or more patients experienced a DLT, regardless of administration sequence, including febrile neutropenia (n=4), grade 4 neutropenia (n=2), grade 4 thrombocytopenia (n=2), and grade 3 aspartate transaminase increase (n=1). The MTD was not established as all cohorts exceeded the MTD by definition. All patients experienced an adverse event; the most frequent all-grade nonhematologic events were fatigue (66.7%), decreased appetite (50.0%), and diarrhea (44.4%). The most frequent grade 3–4 hematologic abnormalities were neutropenia (83.3%), leukopenia (77.8%), and lymphopenia (72.2%). Toxicity was sequence-independent but appeared worse with gemcitabine followed by cabazitaxel. Durable partial responses were observed in three patients (prostate cancer, appendiceal cancer, and melanoma). The unacceptable DLTs with cabazitaxel plus gemcitabine, at doses reduced more than 25% from single-agent doses, preclude further investigation. PMID:26020806

  2. Safety Culture Enhancement Project. Final Report. A Field Study on Approaches to Enhancement of Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Andrew; Hayward, Brent (Dedale Asia Pacific, Albert Park VIC 3206 (Australia))

    2006-08-15

    This report documents a study with the objective of enhancing safety culture in the Swedish nuclear power industry. A primary objective of this study was to ensure that the latest thinking on human factors principles was being recognised and applied by nuclear power operators as a means of ensuring optimal safety performance. The initial phase of the project was conducted as a pilot study, involving the senior management group at one Swedish nuclear power-producing site. The pilot study enabled the project methodology to be validated after which it was repeated at other Swedish nuclear power industry sites, providing a broad-ranging analysis of opportunities across the industry to enhance safety culture. The introduction to this report contains an overview of safety culture, explains the background to the project and sets out the project rationale and objectives. The methodology used for understanding and analysing the important safety culture issues at each nuclear power site is then described. This section begins with a summary of the processes used in the information gathering and data analysis stage. The six components of the Management Workshops conducted at each site are then described. These workshops used a series of presentations, interactive events and group exercises to: (a) provide feedback to site managers on the safety culture and safety leadership issues identified at their site, and (b) stimulate further safety thinking and provide 'take-away' information and leadership strategies that could be applied to promote safety culture improvements. Section 3, project Findings, contains the main observations and output from the project. These include: - a brief overview of aspects of the local industry operating context that impinge on safety culture; - a summary of strengths or positive attributes observed within the safety culture of the Swedish nuclear industry; - a set of identified opportunities for further improvement; - the aggregated

  3. De-Escalating the IT-Projects

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2007-12-01

    Full Text Available Escalation stickins with an ailing project beyond rational justifications. This happens because in the face of negative feedback, decision makers are strangled between whether to stick with or quit the dying project. Environmental uncertainty has been identified as the root cause of the escalatory behavior. This uncertainty emanates from several sources relating to individual, group, organization and broader environmental factors. This paper argues the premise that effective communication can help create an environment whereby workforce can develop an organized action thereby distributing the responsibility across the whole workforce and not the individuals – leading to the possible reduction of escalatory behavior in IT projects.

  4. Safety Hazards During Intrahospital Transport: A Prospective Observational Study.

    Science.gov (United States)

    Bergman, Lina M; Pettersson, Monica E; Chaboyer, Wendy P; Carlström, Eric D; Ringdal, Mona L

    2017-10-01

    To identify, classify, and describe safety hazards during the process of intrahospital transport of critically ill patients. A prospective observational study. Data from participant observations of the intrahospital transport process were collected over a period of 3 months. The study was undertaken at two ICUs in one university hospital. Critically ill patients transported within the hospital by critical care nurses, unlicensed nurses, and physicians. None. Content analysis was performed using deductive and inductive approaches. We detected a total of 365 safety hazards (median, 7; interquartile range, 4-10) during 51 intrahospital transports of critically ill patients, 80% of whom were mechanically ventilated. The majority of detected safety hazards were assessed as increasing the risk of harm, compromising patient safety (n = 204). Using the System Engineering Initiative for Patient Safety, we identified safety hazards related to the work system, as follows: team (n = 61), tasks (n = 83), tools and technologies (n = 124), environment (n = 48), and organization (n = 49). Inductive analysis provided an in-depth description of those safety hazards, contributing factors, and process-related outcomes. Findings suggest that intrahospital transport is a hazardous process for critically ill patients. We have identified several factors that may contribute to transport-related adverse events, which will provide the opportunity for the redesign of systems to enhance patient safety.

  5. De-escalating and escalating treatments for early-stage breast cancer

    DEFF Research Database (Denmark)

    Curigliano, G; Burstein, H J; P Winer, E

    2017-01-01

    The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escal...

  6. The development of an inherent safety approach to the prevention of domino accidents.

    Science.gov (United States)

    Cozzani, Valerio; Tugnoli, Alessandro; Salzano, Ernesto

    2009-11-01

    The severity of industrial accidents in which a domino effect takes place is well known in the chemical and process industry. The application of an inherent safety approach for the prevention of escalation events leading to domino accidents was explored in the present study. Reference primary scenarios were analyzed and escalation vectors were defined. Inherent safety distances were defined and proposed as a metric to express the intensity of the escalation vectors. Simple rules of thumb were presented for a preliminary screening of these distances. Swift reference indices for layout screening with respect to escalation hazard were also defined. Two case studies derived from existing layouts of oil refineries were selected to understand the potentialities coming from the application in the methodology. The results evidenced that the approach allows a first comparative assessment of the actual domino hazard in a layout, and the identification of critical primary units with respect to escalation events. The methodology developed also represents a useful screening tool to identify were to dedicate major efforts in the design of add-on measures, optimizing conventional passive and active measures for the prevention of severe domino accidents.

  7. STUDYING OF SAFETY CLIMATE ASSESSMENT: A CASE STUDY AT STEEL INDUSTRY

    Directory of Open Access Journals (Sweden)

    Hassan DARVISH

    2011-01-01

    Full Text Available Evolution of safety climate used as a practical means has determined and assessed potential problems relevant to safety issues in an organization and can be used in individuals’ performance and work efficiency and decreasing rate of incidents ;as well as; guidance to provide safety organization policy and comparison of safety performance in different organizations. The study wants to determine and prepare safety climate profile and application of its results in improving safety situation. In this study, applied tools presented by Loughborough University are used to evaluate safety climate in one of steel industries and data is collected through questionnaire, group discussions or purposeful interviews and observations, and safety climate score was obtained in 17 scopes. Calculating the score of each safety climate domain and preparing the profile indicated there is the average rate (4.89 2 in the safety climate of the industry.

  8. On safety management and nuclear safety - A frame of reference for studies of safety management with examples from non-nuclear contects of relevance for nuclear safety

    Energy Technology Data Exchange (ETDEWEB)

    Svenson, O.; Allwin, P. [Stockholm Univ. (Sweden); Salo, I. [Lund Univ. (Sweden)

    2004-03-01

    The report includes three case studies of safety management. The studies are presented as chapters, but are written in a format that makes them easy to read separately. Two of the studies cover regulators (the Swedish Civil Aviation Safety Authority, Luftfartsinspektionen) and the Norwegian Petroleum Directorate) and one a regulated activity/industry (a car manufacturer, Volvo Car). The introduction outlines a living system framework and relates this to concepts used in organizational management. The report concludes with some findings with potential relevance for safety management in the nuclear power domain. In the next phase of the work, the regulated counterparts of the regulators here will be investigated in addition to a fourth case study of a regulated activity/industry. (au)

  9. Improving patient safety culture in general practice: an interview study.

    Science.gov (United States)

    Verbakel, Natasha J; de Bont, Antoinette A; Verheij, Theo J M; Wagner, Cordula; Zwart, Dorien L M

    2015-12-01

    When improving patient safety a positive safety culture is key. As little is known about improving patient safety culture in primary care, this study examined whether administering a culture questionnaire with or without a complementary workshop could be used as an intervention for improving safety culture. To gain insight into how two interventions affected patient safety culture in everyday practice. After conducting a randomised control trial of two interventions, this was a qualitative study conducted in 30 general practices to aid interpretation of the previous quantitative findings. Interviews were conducted at practice locations (n = 27) with 24 GPs and 24 practice nurses. The theory of communities of practice--in particular, its concepts of a domain, a community, and a practice--was used to interpret the findings by examining which elements were or were not present in the participating practices. Communal awareness of the problem was only raised after getting together and discussing patient safety. The combination of a questionnaire and workshop enhanced the interaction of team members and nourished team feelings. This shared experience also helped them to understand and develop tools and language for daily practice. In order for patient safety culture to improve, the safety culture questionnaire was more successful when accompanied by a practice workshop. Initial discussion and negotiation of shared goals during the workshop fuelled feelings of coherence and belonging to a community wishing to learn about enhancing patient safety. Team meetings and day-to-day interactions enhanced further liaison and sharing, making patient safety a common and conscious goal. © British Journal of General Practice 2015.

  10. Tobacco and the Escalating Global Cancer Burden

    Directory of Open Access Journals (Sweden)

    Richard F. Oppeltz

    2011-01-01

    Full Text Available The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world.

  11. Canadian Consumer Food Safety Practices and Knowledge: Foodbook Study.

    Science.gov (United States)

    Murray, Regan; Glass-Kaastra, Shiona; Gardhouse, Christine; Marshall, Barbara; Ciampa, Nadia; Franklin, Kristyn; Hurst, Matt; Thomas, M Kate; Nesbitt, Andrea

    2017-10-01

    Understanding consumers' food safety practices and knowledge supports food safety education for the prevention of foodborne illness. The objective of this study was to describe Canadian consumer food safety practices and knowledge. This study identifies demographic groups for targeted food safety education messaging and establishes a baseline measurement to assess the effectiveness of food safety interventions over time. Questions regarding consumer food safety practices and knowledge were included in a population-based telephone survey, Foodbook, conducted from November 2014 to March 2015. The results were analyzed nationally by age group and by gender. The results showed that approximately 90% of Canadians reported taking the recommended cleaning and separating precautions when handling raw meat to prevent foodborne illness. Only 29% of respondents reported using a food thermometer when cooking any meat, and even fewer (12%) reported using a food thermometer for small cuts of meat such as chicken pieces. The majority (>80%) of Canadians were aware of the foodborne illness risks related to chicken and hamburger, but fewer (food safety education in Canada should focus on increasing people's awareness of high-risk foods, specifically foods for which the awareness of risk found in this study was low; targeting messaging to demographic groups as appropriate; and promoting the use of food thermometers when cooking meat and poultry.

  12. Study Gives Good Odds on Nuclear Reactor Safety

    Science.gov (United States)

    Russell, Cristine

    1974-01-01

    Summarized is data from a recent study on nuclear reactor safety completed by Norman C. Rasmussen and others. Non-nuclear events are about 10,000 times more likely to produce large accidents than nuclear plants. (RH)

  13. Benefits and unintended consequences of antimicrobial de-escalation: Implications for stewardship programs.

    Directory of Open Access Journals (Sweden)

    Josie Hughes

    Full Text Available Sequential antimicrobial de-escalation aims to minimize resistance to high-value broad-spectrum empiric antimicrobials by switching to alternative drugs when testing confirms susceptibility. Though widely practiced, the effects de-escalation are not well understood. Definitions of interventions and outcomes differ among studies. We use mathematical models of the transmission and evolution of Pseudomonas aeruginosa in an intensive care unit to assess the effect of de-escalation on a broad range of outcomes, and clarify expectations. In these models, de-escalation reduces the use of high-value drugs and preserves the effectiveness of empiric therapy, while also selecting for multidrug-resistant strains and leaving patients vulnerable to colonization and superinfection. The net effect of de-escalation in our models is to increase infection prevalence while also increasing the probability of effective treatment. Changes in mortality are small, and can be either positive or negative. The clinical significance of small changes in outcomes such as infection prevalence and death may exceed more easily detectable changes in drug use and resistance. Integrating harms and benefits into ranked outcomes for each patient may provide a way forward in the analysis of these tradeoffs. Our models provide a conceptual framework for the collection and interpretation of evidence needed to inform antimicrobial stewardship.

  14. Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis.

    Science.gov (United States)

    Taxonera, Carlos; Barreiro-de Acosta, Manuel; Calvo, Marta; Saro, Cristina; Bastida, Guillermo; Martín-Arranz, María D; Gisbert, Javier P; García-Sánchez, Valle; Marín-Jiménez, Ignacio; Bermejo, Fernando; Chaparro, María; Ponferrada, Ángel; Martínez-Montiel, María P; Pajares, Ramón; de Gracia, Celia; Olivares, David; Alba, Cristina; Mendoza, Juan L; Fernández-Blanco, Ignacio

    2015-10-01

    The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.

  15. Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation.

    Science.gov (United States)

    Desai, Ankit K; Walters, Crista K; Cope, Heidi L; Kazi, Zoheb B; DeArmey, Stephanie M; Kishnani, Priya S

    2017-12-23

    Patients with Pompe disease have realized significant medical benefits due to enzyme replacement therapy (ERT) infusions with alglucosidase alfa. However, regular infusions are time-consuming. Utilizing recommended infusion rates, infusion duration is 3h 45min for a patient receiving the standard dose of 20mg/kg, not including additional time needed for preparation of ERT, assessment of vital signs, intravenous access, and post-infusion monitoring. Recent studies have demonstrated increased effectiveness of higher dose of ERT (40mg/kg) in infantile-onset Pompe disease (IOPD), which increases the infusion duration to 6h 36min. Increased infusion durations compound the psychosocial burden on patients and families and potentially further disrupt family activities and obligations. We developed a stepwise infusion rate escalation protocol to administer higher dose ERT safely while decreasing infusion duration, which has been implemented in 15 patients to date. Reported here in detail are five patients with IOPD on 40mg/kg/weekly ERT in whom infusion duration was decreased with individualized, stepwise rate escalation. All patients tolerated rate escalations above the recommended rates without experiencing any infusion associated reactions and experienced a reduction in infusion duration by 1h and 24min with a corresponding increase in reported satisfaction. Our experience with ERT rate escalation is presented. A careful stepwise method of enzyme replacement therapy (ERT) rate escalation can safely reduce infusion duration in patients with Pompe disease. Copyright © 2017. Published by Elsevier Inc.

  16. Tolerability and pharmacokinetics of avanafil, a phosphodiesterase type 5 inhibitor: a single- and multiple-dose, double-blind, randomized, placebo-controlled, dose-escalation study in healthy Korean male volunteers.

    Science.gov (United States)

    Jung, Jinah; Choi, Sangmin; Cho, Sang Heon; Ghim, Jong-Lyul; Hwang, Aekyung; Kim, Unjib; Kim, Bong Sik; Koguchi, Atsushi; Miyoshi, Shinji; Okabe, Hirotaka; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2010-06-01

    Avanafil is a selective phosphodiesterase type 5 inhibitor being developed for the treatment of erectile dysfunction. This study was conducted to meet Korean regulatory requirements for the marketing of avanafil. To this end, tolerability and pharmacokinetic properties of single and multiple oral doses of avanafil in healthy Korean male volunteers were assessed. A double-blind, randomized, placebo-controlled, parallel-group, dose-escalation study was conducted at the Asan Medical Center (Seoul, Korea). Subjects were randomized to receive either drug or placebo in blocks according to each dose. Subjects were randomly allocated to receive 50-, 100-, or 200-mg tablets of avanafil or placebo once daily for 7 days (avanafil:placebo, 8:2 in each dose group). Tolerability was assessed by monitoring vital signs and results of laboratory tests, 12-lead ECGs, and color discrimination tests. Blood samples of approximately 6 mL were collected in heparinized tubes before and 0.1, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after drug administration on days 1 and 7. Plasma concentrations of avanafil were measured using LC-MS/MS. Pharmacokinetic parameters of avanafil on days 1 and 7 were determined by noncompartmental analysis and compared among the 3 dose groups. Of the 32 healthy male subjects initially enrolled, 30 completed the study. The mean (SD) age, height, and weight of the participants were 23.4 (1.7) years, 175.0 (5.4) cm, and 70.3 (8.9) kg, respectively. Adverse events were reported by 20 of 25 subjects (80%) taking avanafil and by 4 of 6 (67%) taking placebo. No serious adverse events were reported, and there were no clinically relevant changes in vital signs, ECG recordings, physical examination findings, or color discrimination test results. All the adverse events resolved spontaneously. Avanafil reached a mean T(max) at 0.33 to 0.52 hour after dosing and then declined, with a mean apparent t1/2 of 5.36 to 10.66 hours. AUC and C(max) were proportional

  17. Patient perspectives on barriers and enablers to the use and effectiveness of de-escalation techniques for the management of violence and aggression in mental health settings.

    Science.gov (United States)

    Price, Owen; Baker, John; Bee, Penny; Grundy, Andrew; Scott, Anne; Butler, Debbie; Cree, Lindsey; Lovell, Karina

    2017-10-30

    Investigate patient perspectives on barriers and enablers to the use and effectiveness of de-escalation techniques for aggression in mental health settings. De-escalation techniques are the recommended first-line intervention for the management of aggression in mental health settings internationally, yet use of higher risk restrictive practices persists. This indicates de-escalation techniques are not used at optimum frequency and/or there are important factors limiting their use and effect. Descriptive qualitative research using semi-structured interviews and Framework Analysis. Inpatient interviews (N = 26) exploring staff, patient and environmental factors influencing the use and effectiveness of staff de-escalation were conducted mid-2014. Three service user researchers led analysis. Data were synthesized in three deductive themes relating to staff, patient and environmental influences on the use and effectiveness of de-escalation techniques. The dominant view was that restrictive practices, rather than de-escalation techniques, are used in response to escalating patient behaviour. Under-use of de-escalation techniques was attributed to: lack of staff reflection on culture and practice and a need to retain control/dominance over patients. Ward rules, patient factors and a lack of staff respect for patients diluted their effectiveness. Participants identified a systematic process of de-escalation, rule subversion, reduced social distance and staff authenticity as enablers of effective de-escalation. This study investigated patient perspectives on staff, patient and environmental influences on the use and effectiveness of de-escalation techniques. Our framework of barriers and enablers provides indicators of organizational/behaviour change targets for interventions seeking to reduce violence and restrictive practices through enhanced de-escalation techniques. © 2017 John Wiley & Sons Ltd.

  18. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

    Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  19. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers.

    Science.gov (United States)

    Raut, Ashwinikumar A; Rege, Nirmala N; Tadvi, Firoz M; Solanki, Punita V; Kene, Kirti R; Shirolkar, Sudatta G; Pandey, Shefali N; Vaidya, Rama A; Vaidya, Ashok B

    2012-07-01

    Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  20. Safety compliance and safety climate: A repeated cross-sectional study in the oil and gas industry.

    Science.gov (United States)

    Kvalheim, Sverre A; Dahl, Øyvind

    2016-12-01

    Violations of safety rules and procedures are commonly identified as a causal factor in accidents in the oil and gas industry. Extensive knowledge on effective management practices related to improved compliance with safety procedures is therefore needed. Previous studies of the causal relationship between safety climate and safety compliance demonstrate that the propensity to act in accordance with prevailing rules and procedures is influenced to a large degree by workers' safety climate. Commonly, the climate measures employed differ from one study to another and identical measures of safety climate are seldom tested repeatedly over extended periods of time. This research gap is addressed in the present study. The study is based on a survey conducted four times among sharp-end workers of the Norwegian oil and gas industry (N=31,350). This is done by performing multiple tests (regression analysis) over a period of 7years of the causal relationship between safety climate and safety compliance. The safety climate measure employed is identical across the 7-year period. Taking all periods together, the employed safety climate model explained roughly 27% of the variance in safety compliance. The causal relationship was found to be stable across the period, thereby increasing the reliability and the predictive validity of the factor structure. The safety climate factor that had the most powerful effect on safety compliance was work pressure. The factor structure employed shows high predictive validity and should therefore be relevant to organizations seeking to improve safety in the petroleum sector. The findings should also be relevant to other high-hazard industries where safety rules and procedures constitute a central part of the approach to managing safety. Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.

  1. Youth in the midst of escalated political violence: sense of coherence and hope among Jewish and Bedouin Arab adolescents

    National Research Council Canada - National Science Library

    Sarah Abu-Kaf; Orna Braun-Lewensohn; Tehila Kalagy

    2017-01-01

    .... This study aimed to compare coping resources and stress reactions among adolescents from two ethnic groups in southern Israel-Jews and Bedouin Arabs-during a period of escalated political violence (November 2012...

  2. Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Rahimi, Asal, E-mail: asal.rahimi@utsouthwestern.edu [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Thomas, Kimberly; Spangler, Ann [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Rao, Roshni; Leitch, Marilyn; Wooldridge, Rachel; Rivers, Aeisha [Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Seiler, Stephen [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Albuquerque, Kevin; Stevenson, Stella [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Goudreau, Sally [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Garwood, Dan [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Haley, Barbara [Department of Medical Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Euhus, David [Department of Surgery, Johns Hopkins University, Baltimore, Maryland (United States); Heinzerling, John [Department of Radiation Oncology, Levine Cancer Institute, Charlotte, North Carolina (United States); Ding, Chuxiong [University of Texas Southwestern Medical Center, Dallas, Texas (United States); Gao, Ang; Ahn, Chul [Department of Statistics, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Timmerman, Robert [University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2017-05-01

    Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for

  3. Revisiting the cost escalation curse of nuclear power: New lessons from the French experience

    OpenAIRE

    Escobar Rangel, Lina; Lévêque, François

    2012-01-01

    Since the first wave of nuclear reactors in 1970 to the construction of Generation III+ reactors in Finland and France in 2005 and 2007 respectively, nuclear power seems to be doomed to a cost escalation curse. In this paper we reexamine this issue for the French nuclear power fleet. Using the construction costs from the Cour des Comptes report, that was publicly available in 2012, we found that previous studies overestimated the cost escalation. Although, it is undeniable that the scale-up e...

  4. Choosing between stairs and escalators in China: The impact of location, height and pedestrian volume.

    Science.gov (United States)

    Zacharias, John; Tang, Boshen

    2015-01-01

    This research examines whether Beijing residents are more or less likely than Montréal residents to avoid stair climbing, by replicating a study in Montréal, Canada that measured the impacts of distance between stairs and escalator, height between floors and pedestrian volume on stair climbing rate. 15 stairways, 14 up-escalators and 13 down-escalators were selected in 13 publicly accessible settings in Beijing. Distance between the bottom or top of nearest stair and escalator combinations varied from 2.1 m to 114.1 m with height between floors varying from 3.3 m to 21.7 m. Simultaneous counts were conducted on stair and escalator pairs, for a total of 37,081 counted individuals. In the ascent model, pedestrian volume accounted for 16.3% of variance in stair climbing, 16.4% when height was added and 45.1% when distance was added. In the descent model, 40.9% of variance was explained by pedestrian volume, 41.5% when height was added and 45.5% when distance was added. Separating stairs and escalator is effective in increasing stair climbing in Beijing, accounting for 29% of the variance in stair climbing, compared with 43% in Montreal. As in the Montreal case, distance has less effect on stair use rate when descending. Overall, 25.4% of Beijingers opted for stairs when ascending compared with 20.3% of Montrealers, and for descending 32.8% and 31.1% respectively.

  5. Patients for patient safety in China: a cross sectional study.

    Science.gov (United States)

    Zhang, Qiongwen; Li, Yulin; Li, Jing; Mao, Xuanyue; Zhang, Lijuan; Ying, Qinghua; Wei, Xin; Shang, Lili; Zhang, Mingming

    2012-02-01

    To investigate the baseline status of patients' awareness, knowledge, and attitudes to patient safety in China, and to determine the factors that influence patients' involvement in patient safety. We conducted a cross sectional survey using questionnaires adapted from recent studies on patient safety from outside China. The items included medical errors, infection, medication safety, and other aspects of patient safety. The questionnaire included 17 items and 5 domains. The survey was conducted between Jan. 2009 and Dec. 2010 involving 1000 patients from ten grade-A hospitals in seven provinces or cities in China. Most patients from the surgery departments completed the questionnaires voluntarily and anonymously. Five reviewers independently input the data into Microsoft Excel 2003, and the data were double-checked. Data were analyzed using SPSS 15.0 software for differences in the perceptions and attitudes of patients toward patient safety among different genders, ages, and regions. We distributed 1000 questionnaires and collected 959 completed questionnaires (response rate: 96%). Among the respondents, 58% of patients did not know what medical error is. Sixty-five percent of patients wanted disclosure of all medical errors. After errors occurred, 58% of patients wanted explanations of all possible harms that had resulted. Among 187 patients who had experienced medical errors, 83% of patients had sought appropriate legal action. About 52% of patients understood hospital infection, but 28% patients did not know that infections could occur in hospital. Seventy-eight percent of patients thought that medical staff should wash their hands before examining patients. More than half of the patients (68%) were willing to remind the staff of hygiene if they saw unsanitary conditions in a health clinic. Only 14% of patients knew the side effects of medications that they took. The majority of patients surveyed expressed willingness to contribute to patient safety, but their

  6. A fundamental study for safety in advanced PWR systems

    Energy Technology Data Exchange (ETDEWEB)

    Park, Goon Cherl; Kang, C. S.; Lee, E. C.; Kim, S. N.; Lee, J. S.; Kim, M. H.; Chae, W. S.; Kim, M. H.; Lee, D. H.; No, S. T.; Jeon, G. D.; Lee, T. H.; Kim, B. S.; Park, H. J.; Yoon, J. I.; Kim, J. H.; Jeon, J. H.; Jang, W. H.; Sa, Y. C.; Lee, H. W.; Kim, S. J.; Kim, J. W.; Kim, Y. H.; Lee, S. W.; Yang, C. G.; Kim, Y. S.; Ha, J. B.; Son, M. S.; An, Y. C.; Bae, S. W. [Seoul National University, Seoul (Korea, Republic of)

    1997-07-01

    For the development of integral type small and medium reactor which is remarkably safer than existing plants, the operability of passive safety systems should be studied and its applicability to the integral type reactor should be evaluated. The purposes of this study are to evaluate the characteristics of various passive safety systems and provide the proper data for the future design with performing experiments and developing analytical methodology. Thus in this study, the following techniques for small reactors and passive safety systems subject to this study are evaluated and a part of basic experiments and numerical works necessary to the experiments were performed, First, heat pipes used in containment vessel which removes hear by passive mechanism during accidents, second, natural circulation characteristics for the passive safety analysis of integrated reactor, third, heat evaluation of the effective function of hydraulic valve in passive decay heat removal systems, fifth, the determination of the improved source term for the integral reactor, and the last, passive containment cooling system, which is the first step in the analysis of the integrated safety and the environmental impacts of nuclear power plant. 184 refs., 49 tabs., 188 figs. (author)

  7. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD): an open-label, pilot study

    Science.gov (United States)

    2011-01-01

    Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD). Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8) or failed to tolerate the dose. Results Forty-two patients (70%) completed the study. Twenty-one patients (35%) achieved remission with 8 of the 21 patients (38%) needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20%) patients had adverse events leading to discontinuation. The most common adverse events were headache (35%), nausea, diarrhoea and nasopharyngitis (all 25%). Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434 PMID:21410960

  8. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

    Directory of Open Access Journals (Sweden)

    Crawford Gordon M

    2011-03-01

    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

  9. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  10. SAFETY

    CERN Document Server

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  11. Health and safety in organic farming: a qualitative study.

    Science.gov (United States)

    Soto Mas, Francisco; Handal, Alexis J; Rohrer, Rose E; Tomalá Viteri, Eric

    2017-09-22

    To explore health and safety issues in organic farming, specifically among small farmers in central New Mexico. Participants included 10 certified organic producers and 20 workers. Data were collected through semi-structured interviews and observations. The sample consisted of a young, educated, low experienced population which may differ from conventional farmers. Both producers and workers seemed to be aware of the health risks involved with small-scale farming. Producers presented mixed attitudes towards health and safety, while workers' attitudes were more systematically negative. Perception of risk was generally lower among workers compared to producers. Although health and safety training was not specifically mentioned, most participants seemed to understand the relevance of the work environment for health and safety. Regarding ergonomics, the physical demands of working long hours and having to perform a multitude of tasks that contribute to physical stress were issues of concern. This is one of few studies in the United States exploring health and safety among organic farmers. Although participants reported very few actual incidents, the study identified relevant intrapersonal and behavioral factors that may increase or reduce the risk for disease and injury. Results also point to the need for research that focuses on the psychosocial and contextual factors that may contribute to injury and disease among organic farmers.

  12. Metacarpophalangeal portal safety. An anatomical study.

    Science.gov (United States)

    Limousin, B; Corella, F; Del Campo, B; Fernández, E; Corella, M Á; Ocampos, M; Vázquez, T; Larrainzar-Garijo, R

    2017-12-02

    To quantify the risk of dorsal innervation injury when performing direct metacarpophalangeal joint portals of the second to fifth fingers. An anatomical study of 11 upper limbs of fresh corpses was carried out. After placing them in a traction tower, the metacarpophalangeal portals were developed on both sides of the extensor tendon. The dorsal sensory branches were dissected and the distances between the portal and the nearest nerve were measured by a digital caliper. The portals of all the fingers were compared globally to assess the safest finger and two to two radial and ulnar portals were compared in each of the fingers to assess the safest portal within each finger. The overall comparison of all portals and fingers showed that the third finger is the safest in any of its portals, while the ulnar side of the second and radial of the fourth are the portals with the highest risk of nerve injury (P=8.96·10-5). Comparing two to two of the radial and ulnar portals in each of the fingers showed that the ulnar portal is safer than the radial on the fourth finger (P=.042), while the radial is safer than the ulnar on the fifth finger (P=.003). The third finger was the safest to perform metacarpophalangeal portals, while the ulnar side of the second finger and radial side of the fourth had the highest risk of nerve injury. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Temporal Aspects of Moral Disengagement in School Bullying: Crystallization or Escalation?

    Science.gov (United States)

    Obermann, Marie-Louise

    2013-01-01

    This study investigated the stability and change in bullying behavior and their relation to increases and decreases in moral disengagement, specifically exploring whether crystallization and escalation of disengagement occur. Within a 1-year span, two sets of data were collected. A total of 567 sixth to eighth graders participated in both data…

  14. Agricultural intensification escalates future conservation costs

    Science.gov (United States)

    Phelps, Jacob; Carrasco, Luis Roman; Webb, Edward L.; Koh, Lian Pin; Pascual, Unai

    2013-01-01

    The supposition that agricultural intensification results in land sparing for conservation has become central to policy formulations across the tropics. However, underlying assumptions remain uncertain and have been little explored in the context of conservation incentive schemes such as policies for Reducing Emissions from Deforestation and forest Degradation, conservation, sustainable management, and enhancement of carbon stocks (REDD+). Incipient REDD+ forest carbon policies in a number of countries propose agricultural intensification measures to replace extensive “slash-and-burn” farming systems. These may result in conservation in some contexts, but will also increase future agricultural land rents as productivity increases, creating new incentives for agricultural expansion and deforestation. While robust governance can help to ensure land sparing, we propose that conservation incentives will also have to increase over time, tracking future agricultural land rents, which might lead to runaway conservation costs. We present a conceptual framework that depicts these relationships, supported by an illustrative model of the intensification of key crops in the Democratic Republic of Congo, a leading REDD+ country. A von Thünen land rent model is combined with geographic information systems mapping to demonstrate how agricultural intensification could influence future conservation costs. Once postintensification agricultural land rents are considered, the cost of reducing forest sector emissions could significantly exceed current and projected carbon credit prices. Our analysis highlights the importance of considering escalating conservation costs from agricultural intensification when designing conservation initiatives. PMID:23589860

  15. The social process of escalation: a promising focus for crisis management research.

    Science.gov (United States)

    Bergström, Johan; Dekker, Sidney; Nyce, James M; Amer-Wåhlin, Isis

    2012-06-15

    This study identifies a promising, new focus for the crisis management research in the health care domain. After reviewing the literature on health care crisis management, there seems to be a knowledge-gap regarding organisational change and adaption, especially when health care situations goes from normal, to non-normal, to pathological and further into a state of emergency or crisis. Based on studies of escalating situations in obstetric care it is suggested that two theoretical perspectives (contingency theory and the idea of failure as a result of incomplete interaction) tend to simplify the issue of escalation rather than attend to its complexities (including the various power relations among the stakeholders involved). However studying the process of escalation as inherently complex and social allows us to see the definition of a situation as normal or non-normal as an exercise of power in itself, rather than representing a putatively correct response to a particular emergency. The concept of escalation, when treated this way, can help us further the analysis of clinical and institutional acts and competence. It can also turn our attention to some important elements in a class of social phenomenon, crises and emergencies, that so far have not received the attention they deserve. Focusing on organisational choreography, that interplay of potential factors such as power, professional identity, organisational accountability, and experience, is not only a promising focus for future naturalistic research but also for developing more pragmatic strategies that can enhance organisational coordination and response in complex events.

  16. Study on safety level of RC beam bridges under earthquake

    Science.gov (United States)

    Zhao, Jun; Lin, Junqi; Liu, Jinlong; Li, Jia

    2017-08-01

    This study considers uncertainties in material strengths and the modeling which have important effects on structural resistance force based on reliability theory. After analyzing the destruction mechanism of a RC bridge, structural functions and the reliability were given, then the safety level of the piers of a reinforced concrete continuous girder bridge with stochastic structural parameters against earthquake was analyzed. Using response surface method to calculate the failure probabilities of bridge piers under high-level earthquake, their seismic reliability for different damage states within the design reference period were calculated applying two-stage design, which describes seismic safety level of the built bridges to some extent.

  17. A Cross Sectional Study of Food Safety Related Perceptions and ...

    African Journals Online (AJOL)

    Objective: Obtaining enough information on the knowledge and practices of a target group is essential for the development of effective health education programs. This study was conducted to assess food safety knowledge, perception and practices among women working in a north Indian University. Materials and methods: ...

  18. The uses of exposure and risk in road safety studies.

    NARCIS (Netherlands)

    Braimaister, L. Hakkert, A.-S. & Schagen, I.N.L.G. van

    2003-01-01

    This paper explores the theoretical possibilities of the definition of exposure and risk, discusses the problems associated with the use of exposure and risk and brings a variety of examples of safety studies in which use is made of exposure and risk indicators. The paper sets out with a definition

  19. The uses of exposure and risk in road safety studies.

    NARCIS (Netherlands)

    Hakkert, A.S. & Braimaister, L.

    2002-01-01

    This report explores the theoretical possibilities of defining exposure and risk, discusses the problems associated with the use of exposure and risk, and gives examples of various safety studies in which use is made of exposure and risk indicators. The report sets out with a definition of the three

  20. A Validation Study of the Revised Personal Safety Decision Scale

    Science.gov (United States)

    Kim, HaeJung; Hopkins, Karen M.

    2017-01-01

    Objective: The purpose of this study is to examine the reliability and validity of an 11-item Personal Safety Decision Scale (PSDS) in a sample of child welfare workers. Methods: Data were derived from a larger cross-sectional online survey to a random stratified sample of 477 public child welfare workers in a mid-Atlantic State. An exploratory…

  1. Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer

    Directory of Open Access Journals (Sweden)

    Huang BT

    2017-04-01

    Full Text Available Bao-Tian Huang,1,* Li-Li Wu,1,* Long-Jia Guo,1,* Liang-Yu Xu,1,* Rui-Hong Huang,1 Pei-Xian Lin,2 Jian-Zhou Chen,1,3 De-Rui Li,1 Chuang-Zhen Chen1 1Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, 2Department of Nosocomial Infection Management, The Second Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 3CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom *These authors contributed equally to this work Objective: To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT for patients with upper thoracic esophageal cancer (UTEC using radiobiological evaluation. Methods: Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP, and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET and late esophageal toxicity (LET were also analyzed. Results: Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%, and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13% in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2

  2. Audience reactions to peace journalism: How supporters and critics of the Israeli policy process escalation and de-escalation oriented media frames

    Directory of Open Access Journals (Sweden)

    Stephanie Thiel

    2014-04-01

    Full Text Available This paper reports on an experiment that uses the Israeli-Palestinian conflict as a natural laboratory for studying how recipients make sense of escalation vs. de-escalation oriented news articles. The results of the study indicate that media frames and individual frames have both a direct effect and complex interaction effects on participants’ text understanding. Particularly the effect of media war frames diminishes if they are incongruent with participants’ individual frames, and the propaganda function of reports about violence and human casualties can be neutralized if framed according to a peace frame. If participants had a priori positioned themselves in favor of the perpetrator, they may produce reactance, however.

  3. Alaska Humans Factors Safety Study: The Southern Coastal Area

    Science.gov (United States)

    Chappell, Sheryl L.; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASA-ASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the southern coastal areas, specifically: Anchorage, Dillingham, King Salmon, Kodiak, Cold Bay, Juneau, and Ketchikan. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  4. Lung function measurements in rodents in safety pharmacology studies.

    Science.gov (United States)

    Hoymann, Heinz Gerd

    2012-01-01

    The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step - as part of the "core battery" - lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a "follow-up study." For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF(50)) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies.

  5. Lung function measurements in rodents in safety pharmacology studies

    Directory of Open Access Journals (Sweden)

    Heinz Gerd Hoymann

    2012-08-01

    Full Text Available The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the core battery - lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a follow-up study. For these two stages of safety pharmacology testing, both noninvasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in-vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the noninvasive head-out body plethysmography and the invasive but repeatable body-plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50 or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g. EMEA Guideline 1/2008.It is concluded that both invasive and noninvasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies.

  6. A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Rebecca Lim

    2017-08-01

    Full Text Available Liver cirrhosis is the 6th leading cause of death in adults aged 15–59 years in high-income countries. For many who progress to cirrhosis, the only prospect for survival is liver transplantation. While there is some indication that mesenchymal stem cells may be useful in reversing established liver fibrosis, there are limitations to their widespread use – namely their rarity, the need for extensive serial passaging and the associated potential for genomic instability and cellular senescence. To this end, we propose the use of allogeneic amnion epithelial cells. This clinical trial will assess the safety of intravenously delivered allogeneic human amnion epithelial cells (hAECs in patients with compensated liver cirrhosis. This will also provide clinical data that will inform phases 2 and 3 clinical trials with the ultimate goal of developing hAECs as a therapeutic option for patients with cirrhosis who are at significant risk of disease progression. We will recruit 12 patients with compensated cirrhosis, based on their hepatic venous pressure gradient, for a dose escalation study. Patients will be closely monitored in the first 24 h post-infusion, then via daily telephone interviews until clinical assessment on day 5. Long term follow up will include standard liver tests, transient elastography and hepatic ultrasound. Ethics approval was obtained from Monash Health for this trial 16052A, “A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Liver Fibrosis, A First in Adult Human Study.” The trial will be conducted in accordance to Monash Health Human Ethics guidelines. Outcomes from this study will be disseminated in the form of conference presentations and submission to a peer reviewed journal. This trial has been registered on the Australian and New Zealand Clinical Trials Registry ACTRN12616000437460.

  7. School District Health Care Expense: Moderating the Escalation Rate.

    Science.gov (United States)

    Abel, Gene P.

    1991-01-01

    The cafeteria plan for health insurance benefits employers by reducing the overall escalation of health costs. Employees benefit by tailoring their benefit packages to their needs to including the option to decline coverage because of spouse employment. (MLF)

  8. Amygdala 14-3-3ζ as a novel modulator of escalating alcohol intake in mice.

    Directory of Open Access Journals (Sweden)

    Heidi M B Lesscher

    Full Text Available Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood. We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake. Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake. Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol. This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use.

  9. De-escalation techniques used, and reasons for seclusion and restraint, in a forensic psychiatric hospital.

    Science.gov (United States)

    Kuivalainen, Satu; Vehviläinen-Julkunen, Katri; Louheranta, Olavi; Putkonen, Anu; Repo-Tiihonen, Eila; Tiihonen, Jari

    2017-10-01

    In Finland, the Mental Health Act determines the legal basis for seclusion and restraint. Restrictive measures are implemented to manage challenging situations and should be used as a last resort in psychiatric inpatient care. In the present study, we examined the reasons for seclusion and restraint, as well as whether any de-escalation techniques were used to help patients calm down. Seclusion and restraint files from a 4-year period (1 June 2009-31 May 2013) were retrospectively investigated and analysed by content analysis. Descriptive statistics were calculated. A total of 144 episodes of seclusion and restraint were included to analyse the reasons for seclusion and restraint, and 113 episodes were analysed to examine unsuccessful de-escalation techniques. The most commonly-used techniques were one-to-one interaction with a patient (n = 74, 65.5% of n = 113) and administration of extra medication (n = 37, 32.7% of n = 113). The reasons for seclusion and restraint were threatening harmful behaviour (n = 51, 35.4% of n = 144), direct harmful behaviour (n = 43, 29.9%), indirect harmful behaviour (n = 42, 29.1%), and other behaviours (n = 8, 5.6%). In general, the same de-escalation techniques were used with most patients. Most episodes of seclusion or restraint were due to threats of violence or direct violence. Individual means of self-regulation and patient guidance on these techniques are needed. Additionally, staff should be educated on a diverse range of de-escalation techniques. Future studies should focus on examining de-escalation techniques for the prevention of seclusion. © 2017 Australian College of Mental Health Nurses Inc.

  10. Suicide Attempts in a Longitudinal Sample of Adolescents Followed Through Adulthood: Evidence of Escalation

    Science.gov (United States)

    Goldston, David B.; Daniel, Stephanie S.; Erkanli, Alaattin; Heilbron, Nicole; Doyle, Otima; Weller, Bridget; Sapyta, Jeffrey

    2015-01-01

    Objectives This study was designed to examine escalation in repeat suicide attempts from adolescence through adulthood, as predicted by sensitization models (and reflected in increasing intent and lethality with repeat attempts, decreasing amount of time between attempts, and decreasing stress to trigger attempts) Method In a prospective study of 180 adolescents followed through adulthood after a psychiatric hospitalization, suicide attempts and antecedent life events were repeatedly assessed (M = 12.6 assessments, SD = 5.1) over an average of 13 years, 6 months (SD = 4 years, 5 months). Multivariate logistic, multiple linear, and negative binomial regression models were used to examine patterns over time. Results After age 17-18, the majority of suicide attempts were repeat attempts (i.e., made by individuals with prior suicidal behavior). Intent increased both with increasing age, and with number of prior attempts. Medical lethality increased as a function of age but not recurrent attempts. The time between successive suicide attempts decreased as a function of number of attempts. The amount of precipitating life stress was not related to attempts. Conclusions Adolescents and young adults show evidence of escalation of recurrent suicidal behavior, with increasing suicidal intent and decreasing time between successive attempts. However, evidence that sensitization processes account for this escalation was inconclusive. Effective prevention programs that reduce the likelihood of individuals attempting suicide for the first time (and entering this cycle of escalation), and relapse prevention interventions that interrupt the cycle of escalating suicidal behavior among individuals who already have made attempts are critically needed. PMID:25622200

  11. Suicide attempts in a longitudinal sample of adolescents followed through adulthood: Evidence of escalation.

    Science.gov (United States)

    Goldston, David B; Daniel, Stephanie S; Erkanli, Alaattin; Heilbron, Nicole; Doyle, Otima; Weller, Bridget; Sapyta, Jeffrey; Mayfield, Andrew; Faulkner, Madelaine

    2015-04-01

    This study was designed to examine escalation in repeat suicide attempts from adolescence through adulthood, as predicted by sensitization models (and reflected in increasing intent and lethality with repeat attempts, decreasing amount of time between attempts, and decreasing stress to trigger attempts). In a prospective study of 180 adolescents followed through adulthood after a psychiatric hospitalization, suicide attempts, and antecedent life events were repeatedly assessed (M = 12.6 assessments, SD = 5.1) over an average of 13 years 6 months (SD = 4 years 5 months). Multivariate logistic, multiple linear, and negative binomial regression models were used to examine patterns over time. After age 17-18, the majority of suicide attempts were repeat attempts (i.e., made by individuals with prior suicidal behavior). Intent increased both with increasing age, and with number of prior attempts. Medical lethality increased as a function of age but not recurrent attempts. The time between successive suicide attempts decreased as a function of number of attempts. The amount of precipitating life stress was not related to attempts. Adolescents and young adults show evidence of escalation of recurrent suicidal behavior, with increasing suicidal intent and decreasing time between successive attempts. However, evidence that sensitization processes account for this escalation was inconclusive. Effective prevention programs that reduce the likelihood of individuals attempting suicide for the first time (and entering this cycle of escalation), and relapse prevention interventions that interrupt the cycle of escalating suicidal behavior among individuals who already have made attempts are critically needed. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  12. Safety behavior and work safety climate among landscaping and groundskeeping workers in North Carolina: A pilot study.

    Science.gov (United States)

    Kearney, Gregory D; Balanay, Jo Anne G; Mannarino, Adam J

    2017-01-01

    Each year, the average number of nonfatal occupational injuries among landscaping and groundskeeping workers are consistently above the total number of injuries for all other occupational injuries among worker in the U.S. From 2004 to 2007, fatalities among groundskeepers averaged 13.3 per 100,000 workers compared to an overall rate of 4.0 fatalities per 100,000 for all U.S. workers with the majority reported as either Hispanic or Latino. The aims of this project were to describe the use of personal protective equipment and work safety climate among a sample of landscaping and groundskeeping workers employed by public universities in North Carolina (N = 67). Data from a cross-sectional study was collected among workers using group- administered surveys. Statistical associations with work safety climate were tested between personal, work and safety behavior characteristics with work safety climate scores using one-way ANOVA. Nearly half of workers (49.3%) reported experiencing one or more work-related injuries or illnesses within the past 12 months. While work safety practices were perceived as being very important to management, only 56.7% reported having regular safety meetings. In bivariate analysis, work safety climate scores were significantly lower among those reporting race "other than white" (P = 0.01). This is the first study of its kind to evaluate work safety climate among landscaping and groundskeeping workers. Although self-reported safety practices were moderate, minority workers described their work safety climate as being poor. As a pilot study, these results suggest that employers of landscaping and groundskeeping workers could do more to improve safety climate within the organization with an emphasis on safety training for minority and underrepresented workers.

  13. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer.

    Science.gov (United States)

    Bayet-Robert, Mathilde; Kwiatkowski, Fabrice; Leheurteur, Marianne; Gachon, Françoise; Planchat, Eloïse; Abrial, Catherine; Mouret-Reynier, Marie-Ange; Durando, Xavier; Barthomeuf, Chantal; Chollet, Philippe

    2010-01-01

    Since the improvement of chemotherapy with safe molecules is needed for a better efficacy without supplementary toxicity, we investigated the feasibility and tolerability of the combination of docetaxel and curcumin, a polyphenolic derivative extracted from Curcuma longa root. Fourteen patients were accrued in this open-label phase I trial. At the last dose level of curcumin, three dose-limiting toxicities were observed and two out of three patients at this dose level refused to continue treatment, leading us to define the maximal tolerated dose of curcumin at 8,000 mg/d. Eight patients out of 14 had measurable lesions according to RECIST criteria, with five PR and three SD. Some improvements as biological and clinical responses were observed in most patients. Patients with advanced or metastatic breast cancer were eligible. Docetaxel (100 mg/m(2)) was administered as a 1 h i.v. infusion every 3 w on d 1 for six cycles. Curcumin was orally given from 500 mg/d for seven consecutive d by cycle (from d-4 to d+2) and escalated until a dose-limiting toxicity should occur. The primary endpoint of this study was to determine the maximal tolerated dose of the combination of dose-escalating curcumin and standard dose of docetaxel chemotherapy in advanced and metastatic breast cancer patients. Secondary objectives included toxicity, safety, vascular endothelial growth factor and tumor markers measurements and assessment of objective and clinical responses to the combination therapy. The recommended dose of curcumin is 6,000 mg/d for seven consecutive d every 3 w in combination with a standard dose of docetaxel. From the encouraging efficacy results, a comparative phase II trial of this regimen plus docetaxel versus docetaxel alone is ongoing in advanced and metastatic breast cancer patients.

  14. Phase 1 dose escalation multicenter trial of pracinostat alone and in combination with azacitidine in patients with advanced hematologic malignancies.

    Science.gov (United States)

    Abaza, Yasmin M; Kadia, Tapan M; Jabbour, Elias J; Konopleva, Marina Y; Borthakur, Gautam; Ferrajoli, Alessandra; Estrov, Zeev; Wierda, William G; Alfonso, Ana; Chong, Toh Han; Chuah, Charles; Koh, Liang-Piu; Goh, Boon-Cher; Chang, Julie E; Durkes, Daniel E; Foudray, Maria Cielo; Kantarjian, Hagop M; Dong, Xiao Qin; Garcia-Manero, Guillermo

    2017-12-15

    Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity in patients with advanced solid tumors. Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, the authors conducted a phase 1 study to assess the safety, maximum tolerated dose, recommended phase 2 dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies. Pracinostat was administered orally 3 times a week for 3 weeks on a 28-day cycle. Patients were assigned to 7 dose levels using a 3 + 3 dose escalation design. A total of 44 patients were enrolled, 25 of whom had AML and 14 of whom had myelodysplastic syndrome. The maximum tolerated dose was 120 mg and the recommended phase 2 dose was 60 mg. Two patients with AML achieved a response: 1 complete remission (CR) and 1 complete cytogenetic response. Despite a dose-dependent increase in the plasma concentration of pracinostat, a similar increase in histone acetylation was not observed. As an extension, 10 additional patients with myelodysplastic syndrome were enrolled to assess the safety and efficacy of pracinostat in combination with azacitidine. Six patients achieved a CR and 3 achieved a CR without platelet recovery with no added toxicity. The results of the current study demonstrate that pracinostat is safe, with modest single-agent activity in patients with hematological malignancies. Cancer 2017;123:4851-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. Use of force preferences and perceived effectiveness of actions among Crisis Intervention Team (CIT) police officers and non-CIT officers in an escalating psychiatric crisis involving a subject with schizophrenia.

    Science.gov (United States)

    Compton, Michael T; Demir Neubert, Berivan N; Broussard, Beth; McGriff, Joanne A; Morgan, Rhiannon; Oliva, Janet R

    2011-07-01

    Few studies have examined police officers' use of force toward individuals with schizophrenia, despite the widely disseminated Crisis Intervention Team (CIT) model of partnership between mental health and law enforcement that seeks to reduce use of force and enhance safety of officers and individuals with mental illnesses. This study tested the hypotheses that CIT-trained officers would select a lower level of force, identify nonphysical actions as more effective, and perceive physical force as less effective in an escalating psychiatric crisis, compared with non-CIT-trained officers. Police officers (n = 135)-48 CIT trained and 87 non-CIT trained-completed a survey containing 3 scenario-based vignettes depicting an escalating situation involving a subject with psychosis. Data were analyzed using repeated-measures analyses of variance. Officers escalated their preferred actions across the scenarios. A significant scenario by group interaction indicated that CIT-trained officers chose less escalation (ie, opting for less force at the third scenario) than non-CIT-trained officers. Officers reported decreasing perceived effectiveness of nonphysical action across the 3 scenarios. A significant scenario by group interaction indicated that CIT-trained officers reported a lesser decline in perceived effectiveness of nonphysical actions at the third scenario. CIT-trained officers consistently endorsed lower perceived effectiveness of physical force. Efforts are needed to reduce use of force toward individuals with psychotic disorders. These findings suggest that CIT may be an effective approach. In addition to clinical and programmatic implications, such findings demonstrate a role for clinicians, advocates, and schizophrenia researchers in promoting social justice through partnerships with diverse social sectors.

  16. Federal and tribal lands road safety audits : case studies

    Science.gov (United States)

    2009-12-01

    A road safety audit (RSA) is a formal safety performance examination by an independent, multidisciplinary team. RSAs are an effective tool for proactively improving the safety performance of a road project during the planning and design stages, and f...

  17. Modeling the Relationship between Safety Climate and Safety Performance in a Developing Construction Industry: A Cross-Cultural Validation Study.

    Science.gov (United States)

    Zahoor, Hafiz; Chan, Albert P C; Utama, Wahyudi P; Gao, Ran; Zafar, Irfan

    2017-03-28

    This study attempts to validate a safety performance (SP) measurement model in the cross-cultural setting of a developing country. In addition, it highlights the variations in investigating the relationship between safety climate (SC) factors and SP indicators. The data were collected from forty under-construction multi-storey building projects in Pakistan. Based on the results of exploratory factor analysis, a SP measurement model was hypothesized. It was tested and validated by conducting confirmatory factor analysis on calibration and validation sub-samples respectively. The study confirmed the significant positive impact of SC on safety compliance and safety participation, and negative impact on number of self-reported accidents/injuries. However, number of near-misses could not be retained in the final SP model because it attained a lower standardized path coefficient value. Moreover, instead of safety participation, safety compliance established a stronger impact on SP. The study uncovered safety enforcement and promotion as a novel SC factor, whereas safety rules and work practices was identified as the most neglected factor. The study contributed to the body of knowledge by unveiling the deviations in existing dimensions of SC and SP. The refined model is expected to concisely measure the SP in the Pakistani construction industry, however, caution must be exercised while generalizing the study results to other developing countries.

  18. EXPERIMENTAL AND THEORETICAL STUDIES OF REGIONAL SEISMIC SAFETY (BAIKAL REGION

    Directory of Open Access Journals (Sweden)

    Yu. А. Berzhinsky

    2015-09-01

    Full Text Available  The article reviews problems of regional seismic safety and current programs aimed at earthquake proofing of buildings, houses, facilities and life-support systems. It describes the main scientific methodological principles for certification of buildings and facilities located in earthquake-prone regions. With reference to case studies of Angarsk, Shelekhov and Baikalsk and data on Ulaan Baatar (jointly studied with ICAG of the Academy of Sciences of Mongolia, examples of the certification method application in practice are described. Special attention is given to monitoring of the technical status of bearing-wall apartment buildings and houses built in 1960s and 1970s. Cooperation between the Laboratory of Earthquake-Proof Construction and leading scientific research institutes of Russia is reviewed specifically within the framework of the Federal Seismic Safety Program and participation of the Laboratory in development of the national standard titled GOST R Earthquake Intensity Scale.  

  19. A study on safety assessment methodology for a vitrification plant

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Y. C.; Lee, G. S.; Choi, Y. C.; Kim, G. H. [Yonsei Univ., Seoul (Korea, Republic of)

    2002-03-15

    In this study, the technical and regulatory status of radioactive waste vitrification technologies in foreign and domestic plants is investigated and analyzed, and then significant factors are suggested which must be contained in the final technical guideline or standard for the safety assessment of vitrification plants. Also, the methods to estimate the stability of vitrified waste forms are suggested with property analysis of them. The contents and scope of the study are summarized as follows : survey of the status on radioactive waste vitrification technologies in foreign and domestic plants, survey of the characterization methodology for radioactive waste form, analysis of stability for vitrified waste forms, survey and analysis of technical standards and regulations concerned with them in foreign and domestic plants, suggestion of significant factors for the safety assessment of vitrification plants, submission of regulated technical standard on radioactive waste vitrification plats.

  20. Study on the fiber grating sensors in concrete safety monitoring

    Science.gov (United States)

    Liu, Hang; Li, Yang; Zhang, Yu-hong

    2014-09-01

    The concrete may be damaged because there are freeze-thaw cycles between winter and summer in cold regions. Strain is an alternative parameter which can be used to describe deformation. In this paper, the fiber bragg gratings(FBG) were used to concrete safety monitoring. The strain and temperature sensing properties have been studied. The fiber reinforced polymers (FRP) were used for the packaged techniques of FBG sensors. The neural network was applied to temperature compensation for FBG sensors.

  1. Case study: the Argentina Road Safety Project: lessons learned for the decade of action for road safety, 2011-2020.

    Science.gov (United States)

    Raffo, Veronica; Bliss, Tony; Shotten, Marc; Sleet, David; Blanchard, Claire

    2013-12-01

    This case study of the Argentina Road Safety Project demonstrates how the application of World Bank road safety project guidelines focused on institution building can accelerate knowledge transfer, scale up investment and improve the focus on results. The case study highlights road safety as a development priority and outlines World Bank initiatives addressing the implementation of the World Report on Road Traffic Injury's recommendations and the subsequent launch of the Decade of Action for Road Safety, from 2011-2020. The case study emphasizes the vital role played by the lead agency in ensuring sustainable road safety improvements and promoting the shift to a 'Safe System' approach, which necessitated the strengthening of all elements of the road safety management system. It summarizes road safety performance and institutional initiatives in Argentina leading up to the preparation and implementation of the project. We describe the project's development objectives, financing arrangements, specific components and investment staging. Finally, we discuss its innovative features and lessons learned, and present a set of supplementary guidelines, both to assist multilateral development banks and their clients with future road safety initiatives, and to encourage better linkages between the health and transportation sectors supporting them.

  2. A multicenter prospective randomized study comparing the efficacy of escalating higher biphasic versus low biphasic energy defibrillations in patients presenting with cardiac arrest in the in-hospital environment.

    Science.gov (United States)

    Anantharaman, Venkataraman; Tay, Seow Yian; Manning, Peter George; Lim, Swee Han; Chua, Terrance Siang Jin; Tiru, Mohan; Charles, Rabind Antony; Sudarshan, Vidya

    2017-01-01

    Biphasic defibrillation has been practiced worldwide for >15 years. Yet, consensus does not exist on the best energy levels for optimal outcomes when used in patients with ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT). This prospective, randomized, controlled trial of 235 adult cardiac arrest patients with VF/VT was conducted in the emergency and cardiology departments. One group received low-energy (LE) shocks at 150-150-150 J and the other escalating higher-energy (HE) shocks at 200-300-360 J. If return of spontaneous circulation (ROSC) was not achieved by the third shock, LE patients crossed over to the HE arm and HE patients continued at 360 J. Primary end point was ROSC. Secondary end points were 24-hour, 7-day, and 30-day survival. Both groups were comparable for age, sex, cardiac risk factors, and duration of collapse and VF/VT. Of the 118 patients randomized to the LE group, 48 crossed over to the HE protocol, 24 for persistent VF, and 24 for recurrent VF. First-shock termination rates for HE and LE patients were 66.67% and 64.41%, respectively (P=0.78, confidence interval: 0.65-1.89). First-shock ROSC rates were 25.64% and 29.66%, respectively (P=0.56, confidence interval: 0.46-1.45). The 24-hour, 7-day, and 30-day survival rates were 85.71%, 74.29%, and 62.86% for first-shock ROSC LE patients and 70.00%, 50.00%, and 46.67% for first-shock ROSC HE patients, respectively. Conversion rates for further shocks at 200 J and 300 J were low, but increased to 38.95% at 360 J. First-shock termination and ROSC rates were not significantly different between LE and HE biphasic defibrillation for cardiac arrest patients. Patients responded best at 150/200 J and at 360 J energy levels. For patients with VF/pulseless VT, consideration is needed to escalate quickly to HE shocks at 360 J if not successfully defibrillated with 150 or 200 J initially.

  3. Two experiments focusing on de-escalation oriented coverage of post-war conflicts

    Directory of Open Access Journals (Sweden)

    Wilhelm Kempf

    2005-10-01

    Full Text Available War coverage has a strong bias towards the promotion of conflict escalation and - though less pronounced - this bias often survives in post-war coverage as well. Even after the end of war, only a minority of journalists frame conflict in a firmly de-escalation oriented way. Do they have a chance to reach the public? Will their reports be respected by the audience as more balanced and unbiased? Will they have an impact on the audience's mental models of the conflict? Or will the audience continue to cling to its prejudices and reject news articles which do not affirm the enemy images that emerged during wartime? The present paper investigates these questions by means of two experimental studies. In the first experiment, news articles on three events in former Yugoslavia after the fall of Milosevic were presented to a total of n = 128 subjects, representative of the readership of the German quality press: (1 violent conflicts in Southern Serbia (December 2000, (2 the extradition of Milosevic to The Hague (June, 2001 and (3 the treaty between Serbia and Montenegro (March 2003. For each of the events, four different types of articles were used: moderately escalation oriented articles from prestigious German newspapers (Die Welt, Frankfurter Allgemeine Zeitung, Süddeutsche Zeitung and three variants of these articles, (a with increased escalation-oriented framing, (b with moderate de-escalation oriented framing and (c with more strongly de-escalation oriented framing of the events. Each subject was asked to read one article on each of the three events in chronological order and after each article (a to narrate the reported events in their own words and (b to fill out a questionnaire designed to measure the acceptance of the articles as unbiased, well-balanced, interesting, etc. The subjects' mental models of the reported events were inferred from their narratives by means of quantitative content analysis. The second experiment measured the

  4. ROAD ACCIDENT AND SAFETY STUDY IN SYLHET REGION OF BANGLADESH

    Directory of Open Access Journals (Sweden)

    B. K. BANIK

    2011-08-01

    Full Text Available Roads, highways and streets are fundamental infrastructure facilities to provide the transportation for passenger travel and goods movement from one place to another in Sylhet, north–eastern division of Bangladesh with rapid growth of road vehicle, being comparatively developed economic tourist prone area faces severe road traffic accident. Such severe road accidents cause harsh safety hazards on the roads of Sylhet area. This research work presents an overview of the road traffic accident and degraded road safety situation in Sylhet zone which in particular, discusses the key road accident problem characteristics identifying the hazardous roads and spots, most responsible vehicles and related components, conditions of drivers and pedestrians, most victims of accident, effects of accident on society, safety priorities and options available in Sylhet. In this regard, a comprehensive questionnaire survey was conducted on the concerned groups of transportation and detailed accident data was collected from a popular local newspaper. Analysis of the study reveals that Dhaka- Sylhet highway is the most hazardous in road basis and Sylhet Sador thana is the most vulnerable in thana basis in Sylhet region.

  5. De-escalation techniques for psychosis-induced aggression or agitation.

    Science.gov (United States)

    Du, Maolin; Wang, Xuemei; Yin, Shaohua; Shu, Wei; Hao, Ruiqi; Zhao, Sai; Rao, Harish; Yeung, Wan-Ley; Jayaram, Mahesh B; Xia, Jun

    2017-04-03

    Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.De-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user. To investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis. We searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016). Randomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data. We used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis. Of the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial. Using de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting

  6. Premarket safety and efficacy studies for ADHD medications in children.

    Directory of Open Access Journals (Sweden)

    Florence T Bourgeois

    Full Text Available Attention-deficit hyperactivity disorder (ADHD is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing.We identified all ADHD medications approved by the Food and Drug Administration (FDA and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials.A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419. Eleven drugs (55% were approved after <100 participants were studied and 14 (70% after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9, with 5 (38% drugs approved after participants were studied <4 weeks and 10 (77% after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed.Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.

  7. PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Fodor, Andrei; Dell' Oca, Italo; Pasetti, Marcella; Di Muzio, Nadia Gisella [San Raffaele Scientific Institute, Milan (Italy). Dept. of Radiotherapy; Fiorino, Claudio; Broggi, Sara; Cattaneo, Giovanni Mauro; Calandrino, Riccardo [San Raffaele Scientific Institute, Milan (Italy). Medical Physics; Gianolli, Luigi [San Raffaele Scientific Institute, Milan (Italy). Dept. of Nuclear Medicine

    2011-11-15

    To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003). The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection. (orig.)

  8. A study of the costs and benefits of a Formal Safety Program

    Energy Technology Data Exchange (ETDEWEB)

    Crites, T.R.

    1993-03-01

    This study reports on a review of the safety programs and performance at 13 Department of Energy contractor facilities, involving over one-half million man-years of experience. Safety performance was compared with the size of staff and safety department funding over an 11-year period (1980-1990). Indicators of safety performance were taken as lost workdays, recordable injuries, accidental dollar losses, worker radiation dose, and worker`s compensation expenditures. Safety performance was found to be independent of, or even inversely related to, safety investment. Those organizations with the largest safety programs also experienced the greatest accidental losses.

  9. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment

    DEFF Research Database (Denmark)

    Glinatsi, Daniel; Heiberg, Marte S; Rudin, Anna

    2017-01-01

    -to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. METHODS/DESIGN: In a pragmatic, 80-160-week, multicenter, randomized, open......BACKGROUND: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can...... be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head...

  10. A multicenter prospective randomized study comparing the efficacy of escalating higher biphasic versus low biphasic energy defibrillations in patients presenting with cardiac arrest in the in-hospital environment

    Directory of Open Access Journals (Sweden)

    Anantharaman V

    2017-01-01

    Full Text Available Venkataraman Anantharaman,1 Seow Yian Tay,2 Peter George Manning,3 Swee Han Lim,1 Terrance Siang Jin Chua,4 Mohan Tiru,5 Rabind Antony Charles,1 Vidya Sudarshan1 1Department of Emergency Medicine, Singapore General Hospital, 2Department of Emergency Medicine, Tan Tock Seng Hospital, 3Emergency Medicine Department, National University Hospital, 4Department of Cardiology, National Heart Centre, 5Accident and Emergency Department, Changi General Hospital, Singapore Background: Biphasic defibrillation has been practiced worldwide for >15 years. Yet, consensus does not exist on the best energy levels for optimal outcomes when used in patients with ventricular fibrillation (VF/pulseless ventricular tachycardia (VT.Methods: This prospective, randomized, controlled trial of 235 adult cardiac arrest patients with VF/VT was conducted in the emergency and cardiology departments. One group received low-energy (LE shocks at 150–150–150 J and the other escalating higher-energy (HE shocks at 200–300–360 J. If return of spontaneous circulation (ROSC was not achieved by the third shock, LE patients crossed over to the HE arm and HE patients continued at 360 J. Primary end point was ROSC. Secondary end points were 24-hour, 7-day, and 30-day survival.Results: Both groups were comparable for age, sex, cardiac risk factors, and duration of collapse and VF/VT. Of the 118 patients randomized to the LE group, 48 crossed over to the HE protocol, 24 for persistent VF, and 24 for recurrent VF. First-shock termination rates for HE and LE patients were 66.67% and 64.41%, respectively (P=0.78, confidence interval: 0.65–1.89. First-shock ROSC rates were 25.64% and 29.66%, respectively (P=0.56, confidence interval: 0.46–1.45. The 24-hour, 7-day, and 30-day survival rates were 85.71%, 74.29%, and 62.86% for first-shock ROSC LE patients and 70.00%, 50.00%, and 46.67% for first-shock ROSC HE patients, respectively. Conversion rates for further shocks at 200 J and

  11. An analysis of the role of media in conflict escalation:

    OpenAIRE

    Boğa, Gözde; Boga, Gozde

    2006-01-01

    In 25-27 May 2005, a conference entitled “Ottoman Armenians During the Decline of the Empire: Issues of Scientific Responsibility and Democracy,” referred to as the “Armenian conference” in this thesis, was scheduled to be held at Bogaziçi University, Istanbul, Turkey. There were two conflict escalation periods, in May and September 2005 about the conference. Such conflict escalation periods strengthen the parties’ own understanding of the issue and context of conflict; thus, further demarcat...

  12. A study on Impact of Safety Culture on Safety Behavior: Moderating effect of Prevention Focus

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Sun Chul; Jung, Su Jin; Choi, Young Sung [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    In modern society, it has been acknowledged that disasters caused by civilization became inevitable. With growing attention to role of human as one component of the system to cope with accident to prevent disasters, various efforts have been deployed to keep safety. Most of the industries with high hazard have adopted the term as their banner in the efforts to promote safety in their installations and operations. Recently, the Fukushima nuclear power plants(NPPs) accident happened in Japan in 2011 resulted in great impact over the world and have highlighted the importance of safety culture again.

  13. Fusion safety studies in Russia from 1996 to 2000

    Energy Technology Data Exchange (ETDEWEB)

    Kolbasov, B.N. E-mail: kolbasov@nfi.kiae.ru; Biryukov, A.Yu.; Davydov, D.A.; Guseva, M.I.; Khripunov, B.I.; Korshunov, S.N.; Martynenko, Yu.V.; Romanov, P.V.; Vasiliev, V.I

    2001-04-01

    The paper is a review of results of some fusion safety studies performed in Russia during 1996-2000 (after the 6th IAEA Technical Committee Meeting on 'Developments in Fusion Safety'). In particular, changes of hydrogen isotope inventory in co-deposited layers on tungsten and graphite under simulation of normal tokamak operation and plasma disruptions are reported. Size distribution of graphite and W-Be-dust under the experiments at issue revealed two maximums. Erosion products were collected within tokamak T-10. Their microstructure and chemical composition were studied and are reported in the paper. Chemical interaction of beryllium powder with steam (in temperature range of 400-600 deg. C) and air (at 500-1000 deg. C) was investigated. Mathematical models describing it were developed. Chemical interaction of Be-powder with carbon was studied too. A dependence of beryllium carbide layer thickness growth versus time at 950 deg. C was found on the basis of the experiments.

  14. Patient safety education among chinese medical undergraduates: An empirical study.

    Science.gov (United States)

    Li, Gang; Tao, Hong-Bing; Liao, Jia-Zhi; Tang, Jin-Hui; Peng, Fang; Shu, Qin; Li, Wen-Gang; Tu, Shun-Gui; Chen, Zhuo

    2016-10-01

    Patient safety education is conducive to medical students' cognition on patient safety and to improvement of medical quality and safety. Developing patient safety education for medical students is more and more widely recognized by World Health Organization and countries all over the world. However, in China, patient safety courses aiming at medical students are relatively few, and there are few reports about the effect of patient safety courses. This paper explored the influence of patient safety curriculum on medical students' attitude to and knowledge of patient safety. The patient safety curriculum was carried out for 2011-grade undergraduates of Tongji Medical College, Huazhong University of Science and Technology. The students participated in the class according to free choice. After the curriculum, the information of gender, major, attended course, attitude toward patient safety, and knowledge of laws and regulations of the 2011-grade undergraduates were collected. After rejecting invalid questionnaires, the number of undergraduates that participated in the survey was 112 (61 students did not take part in the curriculum; 51 took part in). Chi-square test was applied to analyze patient safety education's influence on medical students' attitude to patient safety and their knowledge mastery situation. The influence of patient safety education on the attitude of medical students to patient safety was not significant, but that on their knowledge of patient safety was remarkable. No matter male or female, as compared with medical students who had not accepted patient safety education, they both had a better acquisition of knowledge after having this education (for male students: 95% CI, 4.556-106.238, P<0.001; for female students: 95% CI, 3.183-33.238, P<0.001). Students majoring in Western Medicine had a relatively better mastery of knowledge of patient safety after receiving patient safety education (95% CI, 6.267-76.271, P<0.001). Short-term patient safety

  15. The social process of escalation: a promising focus for crisis management research

    Directory of Open Access Journals (Sweden)

    Bergström Johan

    2012-06-01

    Full Text Available Abstract Background This study identifies a promising, new focus for the crisis management research in the health care domain. After reviewing the literature on health care crisis management, there seems to be a knowledge-gap regarding organisational change and adaption, especially when health care situations goes from normal, to non-normal, to pathological and further into a state of emergency or crisis. Discussion Based on studies of escalating situations in obstetric care it is suggested that two theoretical perspectives (contingency theory and the idea of failure as a result of incomplete interaction tend to simplify the issue of escalation rather than attend to its complexities (including the various power relations among the stakeholders involved. However studying the process of escalation as inherently complex and social allows us to see the definition of a situation as normal or non-normal as an exercise of power in itself, rather than representing a putatively correct response to a particular emergency. Implications The concept of escalation, when treated this way, can help us further the analysis of clinical and institutional acts and competence. It can also turn our attention to some important elements in a class of social phenomenon, crises and emergencies, that so far have not received the attention they deserve. Focusing on organisational choreography, that interplay of potential factors such as power, professional identity, organisational accountability, and experience, is not only a promising focus for future naturalistic research but also for developing more pragmatic strategies that can enhance organisational coordination and response in complex events.

  16. Escalation to Major Depressive Disorder among adolescents with subthreshold depressive symptoms: evidence of distinct subgroups at risk.

    Science.gov (United States)

    Hill, Ryan M; Pettit, Jeremy W; Lewinsohn, Peter M; Seeley, John R; Klein, Daniel N

    2014-04-01

    The presence of subthreshold depressive symptoms (SubD) in adolescence is associated with high prospective risk of developing Major Depressive Disorder (MDD). Little is known about variables that predict escalation from SubD to MDD. This study used a longitudinal prospective design in a community sample of adolescents to identify combinations of risk factors that predicted escalation from SubD to MDD. Classification tree analysis was used to identify combinations of risk factors that improved the sensitivity and specificity of prediction of MDD onset among 424 adolescents with a lifetime history of SubD. Of the 424, 144 developed MDD during the follow-up period. Evidence for multiple subgroups was found: among adolescents with poor friend support, the highest risk of escalation was among participants with lifetime histories of an anxiety or substance use disorder. Among adolescents with high friend support, those reporting multiple major life events in the past year or with a history of an anxiety disorder were at highest risk of escalation. Study findings may not inform prevention efforts for individuals who first develop SubD during adulthood. This study did not examine the temporal ordering of predictors involved in escalation from SubD to MDD. Adolescents with a history of SubD were at highest risk of escalation to MDD in the presence of poor friend support and an anxiety or substance use disorder, or in the presence of better friend support, multiple major life events, and an anxiety disorder. Findings may inform case identification approaches for adolescent depression prevention programs. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Fire safety case study of a railway tunnel: Smoke evacuation

    Directory of Open Access Journals (Sweden)

    van Maele Karim

    2007-01-01

    Full Text Available When a fire occurs in a tunnel, it is of great importance to assure the safety of the occupants of the tunnel. This is achieved by creating smoke-free spaces in the tunnel through control of the smoke gases. In this paper, results are presented of a study concerning the fire safety in a real scale railway tunnel test case. Numerical simulations are performed in order to examine the possibility of natural ventilation of smoke in inclined tunnels. Several aspects are taken into account: the length of the simulated tunnel section, the slope of the tunnel and the possible effects of external wind at one portal of the tunnel. The Fire Dynamics Simulator of the National Institute of Standards and Technology, USA, is applied to perform the simulations. The simulations show that for the local behavior of the smoke during the early stages of the fire, the slope of the tunnel is of little importance. Secondly, the results show that external wind and/or pressure conditions have a large effect on the smoke gases inside the tunnel. Finally, some idea for the value of the critical ventilation velocity is given. The study also shows that computational fluid dynamics calculations are a valuable tool for large scale, real life complex fire cases. .

  18. The safety of treatment options available for gout.

    Science.gov (United States)

    Schlesinger, Naomi

    2017-04-01

    Gout is the most common inflammatory arthritis in humans. Gout treatment includes rapid initiation of anti-inflammatory medications for acute attacks and chronically treating with urate lowering drugs as well as chronic anti-inflammatory prophylaxis. Areas covered: This review aims to provide an overview and discussion of the safety concerns of current treatment options available for gout. Expert opinion: Gout is a curable disease with appropriate treatment. The advent of new therapies provides encouraging opportunities to improve gout management. However, clinicians should be aware of some of the safety concerns of medications used to treat acute and chronic gout. When prescribing medications for gout one has to be mindful of the presence of comorbidities commonly affecting gout patients that may affect drug safety and efficacy, especially in the elderly and in patients treated with multiple drugs. The benefits of gout drugs, usually, outweigh their safety concerns. Studies are needed in gout patients with chronic kidney disease and/or cardiovascular disease, so that escalation of dosing /combination of anti-inflammatory drugs needed to suppress gouty inflammation as well as escalation of dosing/combination of urate lowering drugs needed to achieve target serum urate level will lead to better understanding of gout treatment safety issues.

  19. A study of the international trend and comprehensive enhancement program on the Nuclear Power Plant safety

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Soon Hong; Cho, Nam Jin; Paek, Won Phil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)] (and others)

    1990-12-15

    The objectives of this study are as follows : overview of the international trend related to the safety of Nuclear Power Plant(NPPs), study of the present status of NPP safety in Korea in aspects of design, construction and operation, suggestion of the comprehensive program to improve NPP safety in Korea. The results of this study can contribute to improve the safety of existing and future NPPs, and to establish the severe accident policy in Korea.

  20. Mucosal healing in inflammatory bowel disease: Maintain or de-escalate therapy.

    Science.gov (United States)

    Cintolo, Marcello; Costantino, Giuseppe; Pallio, Socrate; Fries, Walter

    2016-02-15

    In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing (MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis (UC) and Crohn's disease (CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.

  1. Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee

    Directory of Open Access Journals (Sweden)

    Jonnala Geetha

    2010-07-01

    Full Text Available Abstract Background Extracts of chicory root have anti-inflammatory properties in vitro and in animal models of arthritis. The primary objective of this investigator-initiated, Phase 1, placebo-controlled, double blind, dose-escalating trial was to determine the safety and tolerability of a proprietary bioactive extract of chicory root in patients with osteoarthritis (OA. Secondary objectives were to assess effects on the signs and symptoms of this disorder. Methods Individuals greater than 50 years of age with OA of the hip or knee were eligible for trial entry. A total of 40 patients were enrolled in 3 cohorts and were treated with escalating chicory doses of 600 mg/day, 1200 mg/day and 1800 mg/day for 1 month. The ratio of active treatment to placebo was 5:3 in cohorts 1 and 2 (8 patients each and 16:8 in cohort 3 (24 patients. Safety evaluations included measurement of vital signs and routine lab tests at baseline and the end of the treatment period. Efficacy evaluations at baseline and final visits included self-assessment questionnaires and measurement of the 25-foot walking time. Results In the highest dose cohort, 18 patients who completed treatment per protocol were analyzed for efficacy. In this group, 13 patients showed at least 20% improvement in the defined response domains of pain, stiffness and global assessment: 9 of 10 (90% patients randomized to active treatment with chicory and 4 of 8 (50% patients randomized to placebo (P = 0.06. In general, the treatment was well-tolerated. Only one patient who was treated with the highest dose of chicory had to discontinue treatment due to an adverse event. Conclusions The results of this pilot study suggest that a proprietary bioactive extract of chicory root has a potential role in the management of OA and merits further investigation. Clinicaltrials.gov identifier: NCT 01010919.

  2. Quality management of pharmacology and safety pharmacology studies

    DEFF Research Database (Denmark)

    Spindler, Per; Seiler, Jürg P

    2002-01-01

    Pharmacology has traditionally been excluded from the mandatory application of good laboratory practice (GLP) principles. Consensus has been reached through the process of the International Conference on Harmonisation (ICH, Topic S7A) with regard to the definitions of the different types of pharm......Pharmacology has traditionally been excluded from the mandatory application of good laboratory practice (GLP) principles. Consensus has been reached through the process of the International Conference on Harmonisation (ICH, Topic S7A) with regard to the definitions of the different types...... additional cost. Based on the guidance given in the ICH S7A guideline, it thus appears logical to recommend that test facilities and sponsors consider their organisation of safety pharmacology studies in view of sound study management and formal implementation of GLP, where needed. Organisation of study...

  3. Impact of the World Health Organization's Surgical Safety Checklist on safety culture in the operating theatre: a controlled intervention study

    Science.gov (United States)

    Haugen, A. S.; Søfteland, E.; Eide, G. E.; Sevdalis, N.; Vincent, C. A.; Nortvedt, M. W.; Harthug, S.

    2013-01-01

    Background Positive changes in safety culture have been hypothesized to be one of the mechanisms behind the reduction in mortality and morbidity after the introduction of the World Health Organization's Surgical Safety Checklist (SSC). We aimed to study the checklist effects on safety culture perceptions in operating theatre personnel using a prospective controlled intervention design at a single Norwegian university hospital. Methods We conducted a study with pre- and post-intervention surveys using the intervention and control groups. The primary outcome was the effects of the Norwegian version of the SSC on safety culture perceptions. Safety culture was measured using the validated Norwegian version of the Hospital Survey on Patient Safety Culture. Descriptive characteristics of operating theatre personnel and checklist compliance data were also recorded. A mixed linear regression model was used to assess changes in safety culture. Results The response rate was 61% (349/575) at baseline and 51% (292/569) post-intervention. Checklist compliance ranged from 77% to 85%. We found significant positive changes in the checklist intervention group for the culture factors ‘frequency of events reported’ and ‘adequate staffing’ with regression coefficients at −0.25 [95% confidence interval (CI), −0.47 to −0.07] and 0.21 (95% CI, 0.07–0.35), respectively. Overall, the intervention group reported significantly more positive culture scores—including at baseline. Conclusions Implementation of the SSC had rather limited impact on the safety culture within this hospital. PMID:23404986

  4. The childhood immunization schedule and safety: stakeholder concerns, scientific evidence, and future studies

    National Research Council Canada - National Science Library

    Board on Population Health and Public Health Practice; Institute of Medicine; Committee on the Assessment of Studies of Health Outcomes Related to the Recommended Childhood Immunization Schedule

    2013-01-01

    "The Childhood Immunization Schedule and Safety: Stakeholder Concerns, Scientific Evidence, and Future Studies reviews scientific findings and stakeholders concerns related to the safety of the recommended childhood immunization schedule...

  5. An Intelligent System for Aggression De-escalation Training

    NARCIS (Netherlands)

    Bosse, T.; Gerritsen, C.; de Man, J.

    2016-01-01

    Artificial Intelligence techniques are increasingly being used to develop smart training applications for professionals in various domains. This paper presents an intelligent training system that enables professionals in the public domain to practice their aggression de-escalation skills. The system

  6. Les escales de Likert poden augmentar en sensibilitat?

    Directory of Open Access Journals (Sweden)

    Rafel Bisquerra Alzina

    2015-07-01

    Full Text Available En les investigacions que utilitzen escales tipus Likert s’apliquen principalment escales de 5 punts, sense una fonamentació metodològica que ho justifiqui. La revisió de 3 conegudes revistes permet arribar a aquesta conclusió. Sembla que es fa així per tradició i perquè és difícil posar nom a més de cinc opcions de resposta. En aquest article es posa en qüestió aquesta tradició i s’aporten arguments per proposar altres alternatives. S’analitza la importància de millorar la sensibilitat de les escales augmentant les opcions de resposta; es recomana evitar l’ús de denominacions categòriques, que strictu sensu impedeix el seu ús com a escala d’interval ja que la converteix en nominal (categòrica; s’analitza el rebuig a valors extrems, etc. Com a conseqüència, es recomana la proposta en favor d’escales d’onze punts (de 0 a 10.

  7. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs.

    Science.gov (United States)

    Sapp, John L; Wells, George A; Parkash, Ratika; Stevenson, William G; Blier, Louis; Sarrazin, Jean-Francois; Thibault, Bernard; Rivard, Lena; Gula, Lorne; Leong-Sit, Peter; Essebag, Vidal; Nery, Pablo B; Tung, Stanley K; Raymond, Jean-Marc; Sterns, Laurence D; Veenhuyzen, George D; Healey, Jeff S; Redfearn, Damian; Roux, Jean-Francois; Tang, Anthony S L

    2016-07-14

    Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among

  8. Evolution of pyrrolizidine alkaloid biosynthesis in Apocynaceae: revisiting the defence de-escalation hypothesis.

    Science.gov (United States)

    Livshultz, Tatyana; Kaltenegger, Elisabeth; Straub, Shannon C K; Weitemier, Kevin; Hirsch, Elliot; Koval, Khrystyna; Mema, Lumi; Liston, Aaron

    2018-02-26

    Plants produce specialized metabolites for their defence. However, specialist herbivores adapt to these compounds and use them for their own benefit. Plants attacked predominantly by specialists may be under selection to reduce or eliminate production of co-opted chemicals: the defence de-escalation hypothesis. We studied the evolution of pyrrolizidine alkaloids (PAs) in Apocynaceae, larval host plants for PA-adapted butterflies (Danainae, milkweed and clearwing butterflies), to test if the evolutionary pattern is consistent with de-escalation. We used the first PA biosynthesis specific enzyme (homospermidine synthase, HSS) as tool for reconstructing PA evolution. We found hss orthologues in diverse Apocynaceae species, not all of them known to produce PAs. The phylogenetic analysis showed a monophyletic origin of the putative hss sequences early in the evolution of one Apocynaceae lineage (the APSA clade). We found an hss pseudogene in Asclepias syriaca, a species known to produce cardiac glycosides but no PAs, and four losses of an HSS amino acid motif. APSA clade species are significantly more likely to be Danainae larval host plants than expected if all Apocynaceae species were equally likely to be exploited. Our findings are consistent with PA de-escalation as an adaptive response to specialist attack. © 2018 The Authors New Phytologist © 2018 New Phytologist Trust.

  9. Studying the Relationship between Individual and Organizational Factors and Nurses' Perception of Patient Safety Culture

    OpenAIRE

    Farahnaz Abdolahzadeh; Vahid Zamanzadeh; Aniroda Boroumand

    2012-01-01

    Introduction: Safety culture is considered as an important factor in improving patient safety. Therefore, identifying individual and organizational factors affecting safety culture is crucial. This study was carried out to determine individual and organizational factors associated with nurses' perception of patient safety culture. Methods: The present descriptive study included 940 nurses working in four training hospitals affiliated with Urmia University of Medical Sciences (Iran). Data was ...

  10. CRITICAL SUCCESS FACTORS THAT INFLUENCING SAFETY PROGRAM PERFORMANCE IN MALAYSIAN CONSTRUCTION PROJECTS: CASE STUDIES

    OpenAIRE

    ABDELNASER OMRAN; ABDELWAHAB OMRAN; ABDUL HAMID PAKIR KADIR

    2010-01-01

    The construction industry is characterized as one with a poor safety culture globally. To achieve better site safety performance, emphasis has been placed on implementing effective safety programs. The main aim of this paper is to identify the Critical Success Factors that influencing safety program performance in Malaysian construction projects. In order to accomplish the aim of this study, the following objective was taken into consideration which is to study the factors contributing to the...

  11. On Safety Management. A Frame of Reference for Studies of Safety Management with Examples From Non-Nuclear Contexts of Relevance for Nuclear Safety

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Ola; Salo, Ilkka; Allwin, Pernilla (Risk Analysis, Social and Decision Research Unit, Dept. of Psychology, Stockholm Univ., Stockholm (Sweden))

    2004-11-15

    A good knowledge about safety management from risk technologies outside the area of nuclear power may contribute to both broaden the perspectives on safety management in general, and point at new opportunities for improving safety measures within the nuclear industry. First, a theoretical framework for the study of safety management in general is presented, followed by three case studies on safety management from different non-nuclear areas with potential relevance for nuclear safety. The chapters are written as separate reports and can be read independently of each other. The nuclear industry has a long experience about the management of risky activities, involving all the stages from planing to implementation, both on a more generalized level and in the specific branches of activities (management, administration, operation, maintenance, etc.). Here, safety management is a key concept related to these areas of activities. Outside the field of nuclear power there exist a number of different non-nuclear risk technologies, each one with their own specific needs and experiences about safety management. The differences between the areas consist partly of the different experiences caused by the different technologies. Besides using own experiences in safety practices within the own areas of activities, it may be profitable to take advantage in knowledge and experiences from one area and put it in practice in another area. In order to facilitate knowledge transfer from one technological area to another it may be possible to adapt a common theoretical model, for descriptions and explanations, to the different technologies. Such a model should admit that common denominators for safety management across the areas might be identified and described with common concepts. Systems theory gives the opportunity to not only create models that are descriptive for events within the limits of a given technology, but also to generate knowledge that can be transferred to other

  12. De-escalation: A methodology to reduce coercive measures in clinical psychiatry. A project based on Action Research Principles

    DEFF Research Database (Denmark)

    Lauge Berring, Lene

    The study investigates whether coercive measures and violence can be reduced in psychiatric wards when staff uses a deescalating approach, as the patient's behaviour is escalating. The study is based on action research principles and the objective is to identify, characterize and test deescalating...

  13. Cardiac Safety of Rupatadine in a Single-Ascending-Dose and Multiple-Ascending-Dose Study in Healthy Japanese Subjects, Using Intensive Electrocardiogram Assessments-Comparison With the Previous White Caucasian Thorough QT Study.

    Science.gov (United States)

    Täubel, J; Ferber, G; Fernandes, S; Santamaría, E; Izquierdo, I

    2017-08-01

    A thorough QT/QTc study in healthy white Caucasian subjects demonstrated that rupatadine has no proarrhythmic potential and raised no cardiac safety concerns. The present phase 1 study aimed to confirm the cardiac safety of rupatadine in healthy Japanese subjects. In this randomized, double-blind, placebo-controlled study, 27 healthy Japanese subjects were administered single and multiple escalating rupatadine doses of 10, 20, and 40 mg or placebo. Triplicate electrocardiogram (ECG) recordings were performed on days -1, 1, and 5 at several points, and time-matched pharmacokinetic samples were also collected. Concentration-effect analysis based on the change in the QT interval corrected using Fridericia's formula (QTcF) from average baseline was performed. Data from the formal TQT study in white Caucasian subjects was used for a comparison analysis. The ECG data for rupatadine at doses up to 40 mg did not show an effect on the QTc interval of regulatory concern. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a significant shortening of QTcF on days 1 and 5 four hours after a standardized meal. The data from this study exhibited no statistically significant differences in the QTc effect between Japanese and white Caucasian subjects. © 2017, The American College of Clinical Pharmacology.

  14. Assessment of Electrical Safety Beliefs and Practices: A Case Study

    OpenAIRE

    Boubaker, S.; Mekni, S.; Jerbi, H.

    2017-01-01

    In this paper, the electrical safety beliefs and practices in Hail region, Saudi Arabia, have been assessed. Based on legislative recommendations and rules applied in Saudi Arabia, on official statistics regarding the electricity-caused accidents and on the analysis of more than 200 photos captured in Hail (related to electrical safety), a questionnaire composed of 36 questions (10 for the respondents information, 16 for the home safety culture and 10 for the electrical devices purchasing cul...

  15. The Study on Safety of Scolopendrid Aqua-acupuncture

    Directory of Open Access Journals (Sweden)

    Lim Seung-il

    2004-02-01

    Full Text Available Objective : Recently scolopendrid aqua-acupuncture has been a good effect on pain control but it has not been known about clinical safety. The purpose of this study was to investigate acute toxicity of scolopendrid aqua-acupuncture. Method : In order to prove the clinical safety of scolopendrid aqua-acupuncture, We have observed a bacteriological examination and clinical pathology test after scolopendrid aqua-acupuncture treatment. Balb/c mice were injected intravenous with Scolopendrid aquaacupuncture treatment for and acute toxicity test. We analyzed physical reaction(side effectand clinical pathology test before and after Scolopendrid aqua-acupuncture treatment of mice and 20 patients suffering from pain, who admitted department of Acupunture and Moxibustion, College of Oriental Medicine, Won-Kwang University Kwangju hospital. Results : In the Blood agar plate and Nutrient agar plate, a bacteriological examination did not show a bacillus. In acute toxicity test, there was no mortality thus unable to attain the value. Examining the toxic response in the acute toxicity test, there was no sign of toxication. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. In the 20 patients treated with Scolopendrid aqua-acupuncture, hematologic test did not show remarkable change. In the 20 patients treated with Scolopendrid aqua-acupuncture, Liver function test(AST, ALT, ALP showed a slight decrease on the contrary, and abnormal rate showed a decrease of 5.0% compared with previous study. Reanl function test(BUN, Cr and abnormal rate showed a decrease of 5.0% compared with previous study. In the 20 patients treated with Scolopendrid aqua-acupuncture, Electrolyte were normal range before and after treatment. In the Urine analysis of 20 patients, Leukocyte, Protein, Glucose, Keton, Bilirubin, U-bilinogen were not detected before and after Scolopendrid aqua-acupuncture treatment, and

  16. 7 CFR 1726.251 - Prior approved contract modification related to price escalation on transmission equipment...

    Science.gov (United States)

    2010-01-01

    ... escalation on transmission equipment, generation equipment, and generation construction contracts. 1726.251 Section 1726.251 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES... escalation on transmission equipment, generation equipment, and generation construction contracts. (a...

  17. Assessment of Safety Condition in One of the Teaching Hospitals in Kermanshah (2015: A Case Study

    Directory of Open Access Journals (Sweden)

    Masod Ghanbari Kakavand

    2016-09-01

    Full Text Available Background & Aims of the Study: Many working conditions-related stress factors that can produce injuries and illnesses are important in hospital environments. So, the health and safety of nurses and patients from workplace-induced injuries and illnesses is important. In this study, we have assessed the safety condition of one of the teaching hospitals in Kermanshah (2015. Materials and Methods: This descriptive and cross-sectional study was conducted in one of the teaching hospital of Kermanshah University of medical sciences. For this aim a checklist was prepared based on the Occupational Safety and Health Administration's standards and Part 3 of the manual of National Building Regulations. These checklists comprised (The final checklist had 239 questions of 9 dimensions various sections of safety including; fire safety, building safety, electrical safety, emergency exit routes safety, heating and cooling equipment safety, operating room and laundry room and salty home safety. Eventually, using SPSS 16 and descriptive statistics, data were analyzed. Results: According to the results of this study, 66.6% of the units had poor safety and 33.4% of them were moderately safe. As well as, only ICU and CCU unit, heating and cooling equipment and operational room showed moderate compliance with safety requirements and other sections were poorly complied. Conclusion: The results of this study showed that safety conditions of hospital were not at favorable level. These poor safety statues can jeopardize patients and hospital personnel. Thus some interventions such as improvement of working conditions, compliance with safety acts and implementation of health, safety and environmental management system would be necessary.

  18. Cluster randomized, controlled trial on patient safety improvement in general practice: a study protocol.

    NARCIS (Netherlands)

    Verbakel, N.J.; Langelaan, M.; Verheij, T.J.M.; Wagner, C.; Zwart, D.L.M.

    2013-01-01

    Background: An open, constructive safety culture is key in healthcare since it is seen as a main condition for patient safety. Studies have examined culture improvement strategies in hospitals. In primary care, however, not much is known about effective strategies to improve the safety culture yet.

  19. Cluster randomized, controlled trial on patient safety improvement in general practice: a study protocol

    NARCIS (Netherlands)

    Verbakel, N.J.; Langelaan, M.; Verheij, T.J.M.; Wagner, C.; Zwart, D.L.M.

    2013-01-01

    Background: An open, constructive safety culture is key in healthcare since it is seen as a main condition for patient safety. Studies have examined culture improvement strategies in hospitals. In primary care, however, not much is known about effective strategies to improve the safety culture yet.

  20. Key aspects in managing safety when working with multiple contractors: A case study

    NARCIS (Netherlands)

    Drupsteen, L.; Rasmussen, H.B.; Ustailieva, E.; Kampen, J. van

    2015-01-01

    Working with multiple contractors in a shared workplace can introduce and increase safety risks due to complexity. The aim of this study was to explore how safety issues are recognized in a specific case and to identify whether clients and contractors perceive problems similarly. The safety issues

  1. Radiation dose escalation for loco-regional recurrence of breast cancer after mastectomy

    Directory of Open Access Journals (Sweden)

    Skinner Heath D

    2013-01-01

    Full Text Available Abstract Background Radiation is a standard component of treatment for patients with locoregional recurrence (LRR of breast cancer following mastectomy. The current study reports the results of a 10% radiation dose escalation in these patients. Methods 159 patients treated at MD Anderson Cancer Center between 1994-2006 with isolated LRR after mastectomy alone were reviewed. Patients in the standard treatment group (65 pts, 40.9% were treated to 50 Gy comprehensively plus a boost of 10 Gy. The dose escalated group (94 pts, 59.1% was treated to 54 Gy comprehensively and a minimum 12 Gy boost. Median dose in the standard dose and dose escalated group was 60 Gy (±1 Gy, 95% CI and 66 Gy (±0.5 Gy, 95% CI respectively. Median follow up for living patients was 94 months from time of recurrence. Results The actuarial five year locoregional control (LRC rate was 77% for the entire study population. The five year overall survival and disease-free survival was 55% and 41%, respectively. On multivariate analysis, initial tumor size (p = 0.03, time to initial LRR (p = 0.03, absence of gross tumor at the time of radiation (p = 0.001 and Her2 status (p = 0.03 were associated with improved LRC. Five year LRC rates were similar in patients with a complete response to chemotherapy without surgery and patients with a complete surgical excision (77% vs 83%, p = NS, compared to a 63% LRC rate in patients with gross disease at the time of radiation (p = 0.024. LRC rates were 80% in the standard dose group and 75% in the dose escalated group (p = NS. Conclusions While LRR following mastectomy is potentially curable, distant metastasis and local control rates remain suboptimal. Radiation dose escalation did not appear to improve LRC. Given significant local failure rates, these patients are good candidates for additional strategies to improve their outcomes.

  2. Factors Predicting an Escalation of Restrictive Eating During Adolescence.

    Science.gov (United States)

    Haynos, Ann F; Watts, Allison W; Loth, Katie A; Pearson, Carolyn M; Neumark-Stzainer, Dianne

    2016-10-01

    To examine longitudinal risk factors and short-term risk correlates for the development of extreme forms of restrictive eating among adolescent dieters. Data from Project Eating and Activity in Teens and Young Adults, a population-based study of 2,516 students aged 12-18 years, were collected in 1998-1999 (Time 1) and 5 years later (Time 2). Within this sample, 243 adolescents who reported dieting but not engaging in disordered forms of restrictive eating (e.g., fasting, skipping meals) at Time 1 were followed to determine the self-reported psychological, familial, and social variables predicting initiation of disordered restrictive eating at Time 2. To investigate short-term risk correlates of initiating disordered restrictive eating, the same risk factors were also compared cross-sectionally at Time 2 between the dieters who had and had not initiated disordered restrictive eating. Poisson regression models with robust standard errors were fit for each predictor adjusted for covariates. Depressive symptoms and low self-esteem were significantly associated with the initiation of disordered restrictive eating in both longitudinal and cross-sectional analyses. Poor family communication/caring and maternal dieting significantly predicted long-term risk for escalating restrictive eating severity; whereas, individual body image issues (i.e., weight concerns, body dissatisfaction) and social concerns (i.e., weight-related teasing, peer dieting) were significant short-term correlates of initiating disordered restrictive eating. Depressive symptoms and low self-esteem may be especially important targets for risk identification and prevention for disordered restrictive eating. Intervening on family influences may decrease long-term risk, whereas intervening on body image and responses to social influences may decrease short-term risk for disordered restrictive eating. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights

  3. Motorcycle safety device investigation: A case study on airbags

    Indian Academy of Sciences (India)

    Abstract. The present standard for assessing the effectiveness of safety measures for motorcycle riders defined in ISO 13232 is unique and it incorporates evalu- ation by computer simulation supplemented by full-scale crash tests. This report describes the process of using FE (Finite Element) simulations to investigate safety.

  4. Priming Patient Safety Through Nursing Handoff Communication: A Simulation Pilot Study.

    Science.gov (United States)

    Groves, Patricia S; Bunch, Jacinda L; Cram, Ellen; Farag, Amany; Manges, Kirstin; Perkhounkova, Yelena; Scott-Cawiezell, Jill

    2017-11-01

    Understanding how safety culture mechanisms affect nursing safety-oriented behavior and thus patient outcomes is critical to developing hospital safety programs. Safety priming refers to communicating safety values intended to activate patient safety goals. Safety priming through nursing handoff communication was tested as a means by which cultural safety values may affect nursing practice. The mixed-methods pilot study setting was an academic medical center's high-fidelity simulation lab. Twenty nurses were randomized into intervention and control groups. The intervention group received a safety priming intervention; all participants were observed for completing appropriate actions in response to patient safety risks embedded in a scenario. Stimulated recall interviews were conducted following simulation completion. Nurses receiving the safety priming intervention performed slightly but non-significantly more safety actions than nurses who did not (60.5% vs. 57.9% of 43 actions). Implications for both research and practice are discussed for interventions targeting routine versus safety goal-directed nursing actions.

  5. Understanding safety culture in long-term care: a case study.

    Science.gov (United States)

    Halligan, Michelle H; Zecevic, Aleksandra; Kothari, Anita R; Salmoni, Alan W; Orchard, Treena

    2014-12-01

    This case study aimed to understand safety culture in a high-risk secured unit for cognitively impaired residents in a long-term care (LTC) facility. Specific objectives included the following: diagnosing the present level of safety culture maturity using the Patient Safety Culture Improvement Tool (PSCIT), examining the barriers to a positive safety culture, and identifying actions for improvement. A mixed methods design was used within a secured unit for cognitively impaired residents in a Canadian nonprofit LTC facility. Semistructured interviews, a focus group, and the Modified Stanford Patient Safety Culture Survey Instrument were used to explore this topic. Data were synthesized to situate safety maturity of the unit within the PSCIT adapted for LTC. Results indicated a reactive culture, where safety systems were piecemeal and developed only in response to adverse events and/or regulatory requirements. A punitive regulatory environment, inadequate resources, heavy workloads, poor interdisciplinary collaboration, and resident safety training capacity were major barriers to improving safety. This study highlights the importance of understanding a unit's safety culture and identifies the PSCIT as a useful framework for planning future improvements to safety culture maturity. Incorporating mixed methods in the study of health care safety culture provided a good model that can be recommended for future use in research and LTC practice.

  6. A study for safety and health management problem of semiconductor industry in Taiwan.

    Science.gov (United States)

    Chao, Chin-Jung; Wang, Hui-Ming; Feng, Wen-Yang; Tseng, Feng-Yi

    2008-12-01

    The main purpose of this study is to discuss and explore the safety and health management in semiconductor industry. The researcher practically investigates and interviews the input, process and output of the safety and health management of semiconductor industry by using the questionnaires and the interview method which is developed according to the framework of the OHSAS 18001. The result shows that there are six important factors for the safety and health management in Taiwan semiconductor industry. 1. The company should make employee clearly understand the safety and health laws and standards. 2. The company should make the safety and health management policy known to the public. 3. The company should put emphasis on the pursuance of the safety and health management laws. 4. The company should prevent the accidents. 5. The safety and health message should be communicated sufficiently. 6. The company should consider safety and health norm completely.

  7. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma.

    Science.gov (United States)

    Busse, William W; Katial, Rohit; Gossage, David; Sari, Suha; Wang, Bing; Kolbeck, Roland; Coyle, Anthony J; Koike, Masamichi; Spitalny, George L; Kiener, Peter A; Geba, Gregory P; Molfino, Nestor A

    2010-06-01

    Increased eosinophil levels have been linked to airway inflammation and asthma exacerbations. IL-5 is responsible for eosinophil differentiation, proliferation, and activation; IL-5 receptors are expressed on eosinophils and their progenitors, and targeting such receptors induces eosinophil apoptosis. To evaluate the safety profile, pharmacokinetics, and pharmacodynamics of MEDI-563, a humanized mAb targeting the IL-5 receptor alpha chain. Single, escalating, intravenous doses (0.0003-3 mg/kg) of MEDI-563 were administered to subjects with mild atopic asthma (n = 44) over approximately 3 to 30 minutes in this open-label study. Pulmonary function, symptom scores, adverse events, MEDI-563 pharmacokinetics, and levels of C-reactive protein (CRP), IL-6, eosinophil cationic protein (ECP), and eosinophils were evaluated. Mean peripheral blood (PB) eosinophil levels decreased in a dose-dependent fashion (baseline +/- SD, 0.27 +/- 0.2 x 10(3)/microL; 24 hours postdose, 0.01 +/- 0.0 x 10(3)/microL); 94.0% of subjects receiving >or=0.03 mg/kg exhibited levels between 0.00 x 10(3)/microL and 0.01 x 10(3)/microL. Eosinopenia lasted at least 8 or 12 weeks with doses of 0.03 to 0.1 and 0.3 to 3 mg/kg, respectively. ECP levels were reduced from 21.4 +/- 17.2 microg/L (baseline) to 10.3 +/- 7.0 microg/L (24 hours postdose). The most frequently reported adverse events were reduced white blood cell counts (34.1%), nasopharyngitis (27.3%), and increased blood creatine phosphokinase (25.0%). Mean C-reactive protein levels increased approximately 5.5-fold at 24 hours postdose but returned to baseline by study end; mean IL-6 levels increased approximately 3.9-fold to 4.7-fold at 6 to 12 hours postdose, respectively. Pharmacokinetic activity was dose proportional at doses of 0.03 to 3 mg/kg. Single escalating doses of MEDI-563 had an acceptable safety profile and resulted in marked reduction of PB eosinophil counts within 24 hours after dosing. Copyright (c) 2010 American Academy of

  8. Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

    Science.gov (United States)

    Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

    2017-08-01

    The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright

  9. Escalation with Overdose Control Using Ordinal Toxicity Grades for Cancer Phase I Clinical Trials

    Directory of Open Access Journals (Sweden)

    Mourad Tighiouart

    2012-01-01

    Full Text Available We extend a Bayesian adaptive phase I clinical trial design known as escalation with overdose control (EWOC by introducing an intermediate grade 2 toxicity when assessing dose-limiting toxicity (DLT. Under the proportional odds model assumption of dose-toxicity relationship, we prove that in the absence of DLT, the dose allocated to the next patient given that the previously treated patient had a maximum of grade 2 toxicity is lower than the dose given to the next patient had the previously treated patient exhibited a grade 0 or 1 toxicity at the most. Further, we prove that the coherence properties of EWOC are preserved. Simulation results show that the safety of the trial is not compromised and the efficiency of the estimate of the maximum tolerated dose (MTD is maintained relative to EWOC treating DLT as a binary outcome and that fewer patients are overdosed using this design when the true MTD is close to the minimum dose.

  10. Impact of individual resilience and safety climate on safety performance and psychological stress of construction workers: A case study of the Ontario construction industry.

    Science.gov (United States)

    Chen, Yuting; McCabe, Brenda; Hyatt, Douglas

    2017-06-01

    The construction industry has hit a plateau in terms of safety performance. Safety climate is regarded as a leading indicator of safety performance; however, relatively little safety climate research has been done in the Canadian construction industry. Safety climate may be geographically sensitive, thus it is necessary to examine how the construct of safety climate is defined and used to improve safety performance in different regions. On the other hand, more and more attention has been paid to job related stress in the construction industry. Previous research proposed that individual resilience may be associated with a better safety performance and may help employees manage stress. Unfortunately, few empirical research studies have examined this hypothesis. This paper aims to examine the role of safety climate and individual resilience in safety performance and job stress in the Canadian construction industry. The research was based on 837 surveys collected in Ontario between June 2015 and June 2016. Structural equation modeling (SEM) techniques were used to explore the impact of individual resilience and safety climate on physical safety outcomes and on psychological stress among construction workers. The results show that safety climate not only affected construction workers' safety performance but also indirectly affected their psychological stress. In addition, it was found that individual resilience had a direct negative impact on psychological stress but had no impact on physical safety outcomes. These findings highlight the roles of both organizational and individual factors in individual safety performance and in psychological well-being. Construction organizations need to not only monitor employees' safety performance, but also to assess their employees' psychological well-being. Promoting a positive safety climate together with developing training programs focusing on improving employees' psychological health - especially post-trauma psychological

  11. Race and ethnic differences in a multicenter study of home safety with vouchers redeemable for free safety devices.

    Science.gov (United States)

    Pressley, Joyce C; Kiragu, Andrew; Lapidus, Garry; Pomerantz, Wendy J; Ford, Henri; Barlow, Barbara

    2009-07-01

    Most injuries to infants occur at home and are known to have a modifiable component. Additional information on safety behaviors, practices, and device ownership could inform prevention programs aimed at reducing injury-related race and ethnic disparities. This study is a secondary data analysis of race and ethnic differences in home safety using data collected by the Connecticut, Ohio, Pennsylvania, Minnesota, and New York sites of the Injury Free Coalition for Kids. Study participants were English- and Spanish-speaking parents/guardians of infants aged 4 months to 6 months. All participants received a voucher redeemable for free safety devices and educational materials. Five hundred forty-two study participants were 37.8% black, 41.7% Hispanic, 10.5% white, and 10.0% other race. Whites more frequently owned/had safety devices including cabinet latches (chi2 =28.9, p < 0.0001), drawer latches (chi2 =21.4, p < 0.0001), bath thermometers (chi2 =22.5, p < 0.0001), electric outlet covers (chi2 =15.9, p = 0.0004), and poison control number (chi 2=93.8, p < 0.0001). Practice of unsafe behaviors, such as stomach sleep position, was higher in blacks (29.3%) than whites (15.8%) or Hispanics (17.7%) (chi2 =11.8, p < 0.0083). Overall, 62.1% redeemed vouchers, but this varied significantly by ethnicity: blacks (42.2%), non-Hispanic whites (64.6%), and Hispanics (76.3%) (chi2 = 48.5, p < 0.0001). Compared with whites, both blacks and Hispanics were less likely to own a variety of safety devices at baseline, but Hispanics were more likely than blacks to redeem vouchers. This one shot voucher program was effective at increasing device ownership, but was not sufficient alone to achieve population saturation of safety devices.

  12. Human safety study of body lotion containing Kathon CG.

    Science.gov (United States)

    Schwartz, S R; Weiss, S; Stern, E; Morici, I J; Moss, J N; Goodman, J J; Scarborough, N L

    1987-04-01

    The safety of Kathon CG biocide as a preservative in leave-on body lotions was assessed by 2 double-blind studies, using similar protocols. A total of 209 healthy male and female subjects aged 18 to 65 years, 100 in California (72 test subjects, 28 controls) and 109 in Florida (88 test subjects, 21 controls) completed the studies which included pre- and post-use phase diagnostic patch testing with Kathon CG 100 ppm active ingredient, and 13 weeks daily applications of either a test lotion containing Kathon CG 15 ppm active ingredient or a control lotion without Kathon CG. No evidence of irritation or sensitization attributable to use of the biocide was found during regular dermatological examinations during the use phase. Post-use phase patch testing produced negative results in all subjects with the exception of 1 control subject in Florida who had positive readings at the 2- and 4-week post-use phase patch testing. Overall, these studies show there is minimal, if any, risk of adverse effects associated with the use of Kathon CG 15 ppm active ingredient in a leave-on application.

  13. Contractors’ Attitude towards Enhancing Safety Performance: Case Study on Construction Firms in Penang

    Directory of Open Access Journals (Sweden)

    Ulang N. Md

    2014-01-01

    Full Text Available A qualitative study was conducted to investigate the contractors’ attitude towards enhancing the safety performance in construction site. Despite the fact that there are many safety initiatives established by the government, the rates of accidents are still in a critically high condition. Thus the purpose of this research is to study the contractors’ attitude towards enhancing the implementation of safety management system in construction site in order to increase the safety awareness of construction practitioners in construction site and improve the safety condition of construction sites. This study is conducted through oral interviews with the construction practitioners, and visual inspection of construction sites. The attitudes of contractors are evaluated from 3 aspects: Contractors’ efforts in implement and enforce the safety rules, Contractors efforts in overcoming the rate of accidents, and Reasons given by the contractors for not implement safety law.

  14. Deterrence Adrift Mapping Conflict and Escalation in South Asia

    Science.gov (United States)

    2016-06-21

    selective list of conflict flashpoints articulated in the document—namely, “ the unresolved issue of Kashmir , the violation of treaty arrangements on...between India and Pakistan spiked from 2014 through late 2015, meriting an analysis of how an armed conflict might un- fold between the two nuclear... The doctrine is premised on the assump- tion that India will be able to assert escalation control and prevent the ensuing conflict from spiraling out

  15. Diabetes educators in safety-net practices: a qualitative study.

    Science.gov (United States)

    Kahn, Linda S; Glaser, Kathryn; Fox, Chester H; Patterson, Adam

    2011-01-01

    The purpose of this study was to explore the issues and challenges faced by certified diabetes educator (CDE) trainees in providing diabetes self-management education to patients in safety-net practices. Semi-structured interviews were conducted with CDE trainees and a CDE mentor in 2 primary care practices. Transcripts were analyzed using a content-driven immersion-crystallization approach to identify major themes. Four major themes emerged from the qualitative interview data: (1) patient recruitment approaches, (2) patient barriers to attending diabetes education classes, (3) teaching challenges, and (4) CDE integration into the practices. This study underscores the need for diabetes educators and other health education professionals to be creative and flexible in delivering self-management education to patients in underserved settings. The complexity of diabetes care and the self-care responsibilities placed on the patient reinforce the need for a team approach such as that proposed in the medical home model and should include certified diabetes educators.

  16. Indian reservation safety improvement program : a methodology and case study.

    Science.gov (United States)

    2015-11-01

    Improving roadway safety on Indian reservations requires a comprehensive approach. Limited : resources, lack of crash data, and few cross-jurisdictions coordination has made it difficult for : Native American communities to address their roadway safe...

  17. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  18. Macroscopic broadband optical escalator with force-loaded transformation optics.

    Science.gov (United States)

    Gao, Dongliang; Qiu, Cheng-Wei; Gao, Lei; Cui, Tiejun; Zhang, Shuang

    2013-01-14

    Transformation optics enables one to guide and control light at will using metamaterials. However the designed device is deterministic and not flexible for different objects. Based on force-loaded transformation optics we propose a force-induced transformational device, which can realize dynamic escalator metamorphosing continuously between optical elevator and invisibility cloak. This escalator can visually lift up and down the perceived height of a plane fixed in space by controlling the forces loaded in different directions. Or conversely, the escalator can physically lift up and down a plane while visually maintaining the same height to an outside observer. One can quickly adjust this device to the required demand without changing the background index, while the usual transformation cloak will be detectable due to the lateral shift from mismatched background. The schematic is self-adaptive, multi-functional, and free of metamaterial or nanofabrication. Our work opens a new perspective in controlling light dynamically and continuously, empowering unprecedented applications in military cloak, optic communication, holographic imaging, and phase-involved microtechnique.

  19. Learning to make collective decisions: the impact of confidence escalation.

    Science.gov (United States)

    Mahmoodi, Ali; Bang, Dan; Ahmadabadi, Majid Nili; Bahrami, Bahador

    2013-01-01

    Little is known about how people learn to take into account others' opinions in joint decisions. To address this question, we combined computational and empirical approaches. Human dyads made individual and joint visual perceptual decision and rated their confidence in those decisions (data previously published). We trained a reinforcement (temporal difference) learning agent to get the participants' confidence level and learn to arrive at a dyadic decision by finding the policy that either maximized the accuracy of the model decisions or maximally conformed to the empirical dyadic decisions. When confidences were shared visually without verbal interaction, RL agents successfully captured social learning. When participants exchanged confidences visually and interacted verbally, no collective benefit was achieved and the model failed to predict the dyadic behaviour. Behaviourally, dyad members' confidence increased progressively and verbal interaction accelerated this escalation. The success of the model in drawing collective benefit from dyad members was inversely related to confidence escalation rate. The findings show an automated learning agent can, in principle, combine individual opinions and achieve collective benefit but the same agent cannot discount the escalation suggesting that one cognitive component of collective decision making in human may involve discounting of overconfidence arising from interactions.

  20. Learning to make collective decisions: the impact of confidence escalation.

    Directory of Open Access Journals (Sweden)

    Ali Mahmoodi

    Full Text Available Little is known about how people learn to take into account others' opinions in joint decisions. To address this question, we combined computational and empirical approaches. Human dyads made individual and joint visual perceptual decision and rated their confidence in those decisions (data previously published. We trained a reinforcement (temporal difference learning agent to get the participants' confidence level and learn to arrive at a dyadic decision by finding the policy that either maximized the accuracy of the model decisions or maximally conformed to the empirical dyadic decisions. When confidences were shared visually without verbal interaction, RL agents successfully captured social learning. When participants exchanged confidences visually and interacted verbally, no collective benefit was achieved and the model failed to predict the dyadic behaviour. Behaviourally, dyad members' confidence increased progressively and verbal interaction accelerated this escalation. The success of the model in drawing collective benefit from dyad members was inversely related to confidence escalation rate. The findings show an automated learning agent can, in principle, combine individual opinions and achieve collective benefit but the same agent cannot discount the escalation suggesting that one cognitive component of collective decision making in human may involve discounting of overconfidence arising from interactions.

  1. A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

    Science.gov (United States)

    2014-01-01

    Background Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. Methods A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of

  2. Chemoembolization of Hepatocellular Carcinoma with Hepasphere 30–60 μm. Safety and Efficacy Study

    Energy Technology Data Exchange (ETDEWEB)

    Malagari, Katerina, E-mail: kmalag@otenet.gr [University of Athens, 2nd Department of Radiology (Greece); Pomoni, Maria, E-mail: mpomoni@mail.gr [University of Athens, Imaging and Research Unit (Greece); Moschouris, Hippokratis, E-mail: hipmosch@gmail.com [Tzanion Hospital, Department of Radiology (Greece); Kelekis, Alexios, E-mail: akelekis@cc.uoa.gr [University of Athens, 2nd Department of Radiology (Greece); Charokopakis, Angelos, E-mail: axarok@gmail.com; Bouma, Evanthia, E-mail: boumaevanthia@gmail.com; Spyridopoulos, Themistoklis [University of Athens, Imaging and Research Unit (Greece); Chatziioannou, Achilles, E-mail: ahatzi@cc.uoa.gr [University of Athens, 2nd Department of Radiology (Greece); Sotirchos, Vlasios, E-mail: sotirchos@hotmail.com [University of Athens, Imaging and Research Unit (Greece); Karampelas, Theodoros, E-mail: ctamvakop@bioacademy.gr; Tamvakopoulos, Constantin, E-mail: ctamvakop@bioacademy.gr [Research Academy of University of Athens (Greece); Filippiadis, Dimitrios, E-mail: dfilippiadis@yahoo.gr [University of Athens, 2nd Department of Radiology (Greece); Karagiannis, Enangelos, E-mail: kmalag@otenet.gr [University of Athens, Imaging and Research Unit (Greece); Marinis, Athanasios, E-mail: drmarinis@gmail.com [Tzanion Hospital, 1st Department of Surgery (Greece); Koskinas, John, E-mail: koskinas@ath.forthnet.gr [University of Athens, 2nd Department of Internal Medicine and Hepatology (Greece); Kelekis, Dimitrios A., E-mail: dkelekis@med.uoa.gr [University of Athens, Imaging and Research Unit, 2nd Department of Radiology (Greece)

    2013-11-22

    Background: This study examined the safety, pharmacokinetics, and efficacy of transarterial chemoembolization of hepatocellular carcinoma (HCC) using a newly developed size of a superabsorbent polymer drug-eluting embolic material.MethodsForty-five patients with documented HCC (Child–Pugh score A/B: 55.5 %/44.5 %) were embolized with HepaSphere microspheres 30–60 μm with escalation of lesion, dose, and frequency of re-embolization. Local response was evaluated with modified response evaluation criteria in solid tumors (mRECIST). Plasma levels of doxorubicin were measured in 24 patients at baseline and at 5, 20, 40, 60, and 120 min, at 6, 24, and 48 h, and at 7 days, respectively, to determine doxorubicin in plasma (Cmax) and area under the curve (AUC). Measurements of three patients who underwent lipiodol-based conventional chemoembolization (c-TACE) were also performed.ResultsTACE with HepaSphere was well tolerated with an acceptable safety profile and no 30-day mortality. Response rates were calculated on intention-to-treat basis with complete response (CR) in 17.8 % reaching 22.2 % for the target lesion. Overall partial response (PR) was seen in 51.1 %, stable disease in 20 %, and progressive disease in 11.1 % of patients. Overall objective response (CR + PR), including patients treated at all dosages of doxorubicin, was seen in 68.9 % of cases. After a median follow-up of 15.6 months, 1-year survival is 100 %. Doxorubicin AUC was significantly lower in patients with HepaSphere 30–60 μm (35,195 ± 27,873 ng × min/ml) than in patients with conventional TACE (103,960 ± 16,652 ng × min/ml; p = 0.009). Cmax was also significantly lower with HepaSphere 30–60 μm (83.9 ± 32.1 ng/ml) compared with c-TACE (761.3 ± 58.8 ng/ml; p = 0.002).ConclusionHepaSphere 30–60 μm is an effective drug-eluting embolic material with a favourable pharmacokinetic profile.

  3. Validation of treatment escalation as a definition of atopic eczema flares.

    Directory of Open Access Journals (Sweden)

    Kim S Thomas

    Full Text Available Atopic eczema (AE is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured.To validate two concepts of AE flares based on daily reports of topical medication use: (i escalation of treatment and (ii days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors.Data from two published AE studies (studies A (n=336 and B (n=60 were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10 as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC curve for binary outcome measures.Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only. Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks.Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control.Current Controlled Trials ISRCTN71423189 (Study A.

  4. Assessment of Electrical Safety Beliefs and Practices: A Case Study

    Directory of Open Access Journals (Sweden)

    S. Boubaker

    2017-12-01

    Full Text Available In this paper, the electrical safety beliefs and practices in Hail region, Saudi Arabia, have been assessed. Based on legislative recommendations and rules applied in Saudi Arabia, on official statistics regarding the electricity-caused accidents and on the analysis of more than 200 photos captured in Hail (related to electrical safety, a questionnaire composed of 36 questions (10 for the respondents information, 16 for the home safety culture and 10 for the electrical devices purchasing culture has been devised and distributed to residents. 228 responses have been collected and analyzed. Using a scale similar to the one adopted for a university student GPA calculation, the electrical safety level (ESL in Hail region has been found to be 0.76 (in a scale of 4 points which is a very low score and indicates a poor electrical safety culture. Several recommendations involving different competent authorities have been proposed. Future work will concern the assessment of safety in industrial companies in Hail region.

  5. Pharmacokinetics and safety of paroxetine controlled-release tablet in healthy Chinese subjects: a single-dose three-period crossover study.

    Science.gov (United States)

    Chen, Rui; Shen, Kai; Hu, Pei

    2016-02-01

    To evaluate the pharmacokinetics of paroxetine controlledrelease tablets after single oral administrations and its safety profile in healthy Chinese subjects. This was a phase I, openlabel, single-dose, three-period crossover study in which 12 healthy subjects received single oral doses of 12.5, 25, 37.5 mg paroxetine controlled-release tablets with 10-day washout between doses. Serial venous blood samples were collected for 96 hours after study drug administration and analyzed with LC-MS/MS. Pharmacokinetic parameters of paroxetine were calculated using non-compartmental analysis with Win-Nonlin software. The absorption of controlled-release paroxetine was delayed with a median tmax of 8 - 10 hours and the mean t1/2 was 12 - 14 hours across all doses. Over the dose range of 12.5 - 37.5 mg, the mean Cmax increased from 2.62 to 15.13 ng/mL and AUC0-∞ increased from 63.56 to 404.91 h×ng/mL. The 90% CI for the ratio of dose-normalized mean values of Cmax and AUC were not contained within the criteria limits, indicating a greater than doseproportional increase. All reported adverse events were considered to be mild. Plasma exposure of controlled-release paroxetine increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. Paroxetine controlled-release tablet was well tolerated in healthy Chinese subjects.

  6. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Clark, Catharine; Bidmead, A. Margaret [Institute of Cancer Research, London (United Kingdom); Department of Physics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); St Rose, Suzanne; Barbachano, Yolanda; A' Hern, Roger [Department of Statistics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L. [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Harrington, Kevin J. [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Nutting, Christopher M., E-mail: chris.nutting@rmh.nhs.uk [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom)

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  7. The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease.

    Science.gov (United States)

    Kwapisz, Lukasz; Gregor, Jamie; Chande, Nilesh; Yan, Brian; Ponich, Terry; Mosli, Mahmoud

    2017-08-01

    Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.

  8. Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lamberto Manzoli

    Full Text Available To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes, directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both.Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up.Direct contact and structured questionnaires by phone or via internet.Adults (30-75 years were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers, users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers, or smokers of both tobacco and e-cigarettes (dual smokers. Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence.Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily.We used linear and logistic regression, with region as cluster unit.Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%. All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35-8.02, whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall.Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e

  9. Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study.

    Science.gov (United States)

    Manzoli, Lamberto; Flacco, Maria Elena; Fiore, Maria; La Vecchia, Carlo; Marzuillo, Carolina; Gualano, Maria Rosaria; Liguori, Giorgio; Cicolini, Giancarlo; Capasso, Lorenzo; D'Amario, Claudio; Boccia, Stefania; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo

    2015-01-01

    To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes), directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both. Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up. Direct contact and structured questionnaires by phone or via internet. Adults (30-75 years) were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers), users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers), or smokers of both tobacco and e-cigarettes (dual smokers). Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence. Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily. We used linear and logistic regression, with region as cluster unit. Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%). All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35-8.02), whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall). Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e

  10. Mahayograj guggulu: Heavy metal estimation and safety studies.

    Science.gov (United States)

    Lavekar, G S; Ravishankar, B; Gaidhani, S; Shukla, V J; Ashok, B K; Padhi, M M

    2010-07-01

    This study was conducted to estimate the heavy metal profile and determine the safety of Mahayograj guggulu, an Ayurvedic herbo-mineral preparation. Mahayograj guggulu, manufactured by Shree Baidynath Ayurved Bhawan Pvt. Ltd., Gwalior Road, Jhansi - 284 003 (of batch number-07 and manufacturing date October 2004) was procured from the local market. Heavy metal concentrations were measured using an atomic absorption spectrophotometer. A total of 40 Charles Foster strain albino rats of either sex with an average body weight of 160-250 g were divided into four groups (Groups I, II, III and IV), with 10 animals in each group. Group I served as the control, while Group II, III and IV rats received Mahayograj guggulu at a dose of 54 (dose equivalent to human therapeutic dose), 270 (five-times the dose equivalent to the human therapeutic dose) and 540 (10-times the dose equivalent to human therapeutic dose) mg/kg, p.o. for 120 days. The effect of drug administration was noted on the ponderal, biochemical, hematological and histopathological parameters. In addition, urine examination was also carried out. At the end of the study, only six rats per group were sacrificed as per the IAEC advice. Mahayograj guggulu was found to be safe at all dose levels tested. No significant behavioral changes were noted in any of the groups studied. The effect on food and water consumption and fecal and urine output remained unaffected in all groups during the study period. No major alterations were observed in hematology, serum biochemistry, necropsy and histopathology at the therapeutically advocated dose level. Heavy metal content measurement indicated levels of 25.8 µg/g for lead, 0.07 µg/g for mercury and 5.19 µg/g for arsenic. The test drug is well tolerated as no changes of a serious nature could be observed in any of the parameters assessed.

  11. The perception of hospital safety culture and selected outcomes among nurses: An exploratory study.

    Science.gov (United States)

    Saleh, Ali M; Darawad, Muhammad W; Al-Hussami, Mahmoud

    2015-09-01

    The objectives of this study were to examine nurses' perceptions of the hospital safety culture in Jordan and to identify the relationships between aspects of hospital safety culture and selected safety outcomes. Data from 242 registered nurses in five Jordanian hospitals were analyzed. Aspects of hospital safety culture and outcomes were measured using the Hospital Survey on Patient Safety Culture. Among various aspects of hospital safety culture, teamwork within units had the highest average percentage of positive responses (49.8%). Additionally, participants reported deficits in other aspects of safety culture, particularly in staffing and nonpunitive response to errors, with average percentages of positive responses of 30.4% and 30.7%, respectively. Pearson correlation analysis revealed that 9 of 10 subscales of hospital safety culture were significantly correlated to one or more of the hospital safety outcomes. The findings of this study can help policymakers and healthcare administrators identify the weaknesses and strengths of hospital safety issues in order to propose effective strategies to improve patient safety and quality of care. © 2015 Wiley Publishing Asia Pty Ltd.

  12. A study on safety measure of LMR coolant

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Sung Tai; Choi, Y. D.; Choi, J. H.; Kim, T. J.; Jeong, K. C.; Kwon, S. W.; Kim, B. H.; Jeong, J. Y.; Park, J. H.; Kim, K. R.; Jo, B. R.

    1997-08-01

    A study on safety measures of LMR coolant showed the results as follows: 1. Sodium fire characteristics. A. Sodium pool temp., gas temp., oxygen concentration calculated by flame combustion model were generally higher than those calculated by surface combustion model. B. Basic and detail designs for medium sodium fire test facility were carried out and medium sodium fire test facility was constructed. 2. Sodium/Cover gas purification technology. A. Construction and operation of calibration loop. B. Purification analysis and conceptual design of the packing for a cold trap. 3. Analysis of sodium-water reaction characteristics. We have investigated the characteristics analysis for micro and small leaks phenomena, development of the computer code for analysis of initial and quasi steady-state spike pressures to analyze large leak accident. Also, water mock-up test facility for the analysis of large leak accident phenomena was designed and manufactured. 4. Development of water leak detection technology. Detection signals were appeared when the hydrogen detector is operated to Ar-H{sub 2} gas system. The technology for the passive acoustic detection with respect to large leakage of water into sodium media was reviewed. And water mock-up test equipment and instrument system were designed and constructed. (author). 19 refs., 45 tabs., 52 figs.

  13. Dynamics of space welding impact and corresponding safety welding study.

    Science.gov (United States)

    Fragomeni, James M; Nunes, Arthur C

    2004-03-01

    This study was undertaken in order to be sure that no hazard would exist from impingement of hot molten metal particle detachments upon an astronauts space suit during any future electron beam welding exercises or experiments. The conditions under which molten metal detachments might occur in a space welding environment were analyzed. The safety issue is important during welding with regards to potential molten metal detachments from the weld pool and cold filler wire during electron beam welding in space. Theoretical models were developed to predict the possibility and size of the molten metal detachment hazards during the electron beam welding exercises at low earth orbit. Some possible ways of obtaining molten metal drop detachments would include an impulse force, or bump, to the weld sample, cut surface, or filler wire. Theoretical models were determined for these detachment concerns from principles of impact and kinetic energies, surface tension, drop geometry, surface energies, and particle dynamics. A weld pool detachment parameter for specifying the conditions for metal weld pool detachment by impact was derived and correlated to the experimental results. The experimental results were for the most part consistent with the theoretical analysis and predictions. c2003 Elsevier Ltd. All rights reserved.

  14. Dynamics of space welding impact and corresponding safety welding study

    Science.gov (United States)

    Fragomeni, James M.; Nunes, Arthur C.

    2004-03-01

    This study was undertaken in order to be sure that no hazard would exist from impingement of hot molten metal particle detachments upon an astronauts space suit during any future electron beam welding exercises or experiments. The conditions under which molten metal detachments might occur in a space welding environment were analyzed. The safety issue is important during welding with regards to potential molten metal detachments from the weld pool and cold filler wire during electron beam welding in space. Theoretical models were developed to predict the possibility and size of the molten metal detachment hazards during the electron beam welding exercises at low earth orbit. Some possible ways of obtaining molten metal drop detachments would include an impulse force, or bump, to the weld sample, cut surface, or filler wire. Theoretical models were determined for these detachment concerns from principles of impact and kinetic energies, surface tension, drop geometry, surface energies, and particle dynamics. A weld pool detachment parameter for specifying the conditions for metal weld pool detachment by impact was derived and correlated to the experimental results. The experimental results were for the most part consistent with the theoretical analysis and predictions.

  15. SU-C-BRB-02: Automatic Planning as a Potential Strategy for Dose Escalation for Pancreas SBRT?

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S; Zheng, D; Ma, R; Lin, C; Zhu, X; Lei, Y; Enke, C; Zhou, S [University of Nebraska Medical Center, Omaha, NE (United States)

    2016-06-15

    Purpose: Stereotactic body radiation therapy (SBRT) has been suggested to provide high rates of local control for locally advanced pancreatic cancer. However, the close proximity of highly radiosensitive normal tissues usually causes the labor-intensive planning process, and may impede further escalation of the prescription dose. The present study evaluates the potential of an automatic planning system as a dose escalation strategy. Methods: Ten pancreatic cancer patients treated with SBRT were studied retrospectively. SBRT was delivered over 5 consecutive fractions with 6 ∼ 8Gy/fraction. Two plans were generated by Pinnacle Auto-Planning with the original prescription and escalated prescription, respectively. Escalated prescription adds 1 Gy/fraction to the original prescription. Manually-created planning volumes were excluded in the optimization goals in order to assess the planning efficiency and quality simultaneously. Critical organs with closest proximity were used to determine the plan normalization to ensure the OAR sparing. Dosimetric parameters including D100, and conformity index (CI) were assessed. Results: Auto-plans directly generate acceptable plans for 70% of the cases without necessity of further improvement, and two more iterations at most are necessary for the rest of the cases. For the pancreas SBRT plans with the original prescription, autoplans resulted in favorable target coverage and PTV conformity (D100 = 96.3% ± 1.48%; CI = 0.88 ± 0.06). For the plans with the escalated prescriptions, no significant target under-dosage was observed, and PTV conformity remains reasonable (D100 = 93.3% ± 3.8%, and CI = 0.84 ± 0.05). Conclusion: Automatic planning, without substantial human-intervention process, results in reasonable PTV coverage and PTV conformity on the premise of adequate OAR sparing for the pancreas SBRT plans with escalated prescription. The results highlight the potential of autoplanning as a dose escalation strategy for pancreas

  16. The safety of field tubal sterilization: a cohort study.

    Science.gov (United States)

    Siswosudarmo, R

    1991-01-01

    A cohort study on female sterilization has been carried out to compare the safety of field-based procedures with hospital-based procedures. A total of 217 women were recruited, consisting of 103 field-based and 114 hospital-based acceptors. Married and healthy women 20-45 years of age, having at least two living children, not obese, no history of major abdominal surgery, no signs of acute pelvic inflammatory disease, and no contraindication to ketamin were included in the study. Women with severe pelvic adhesions encountered during surgery were excluded from the study. The ambulatory procedure was used for all acceptors except those who were sterilized in hospital immediately after delivery. They were asked to come to th Sarjito Hospital (hospital-based) or Puskesmas (primary health care center or field-based), after fasting the night before. Ketamin, 50-100 mg, was used intravenously for general anesthesia. Minilaparotomy followed by the Pomeroy method was used for standard female tubal sterilization. Tetracycline, 3 x 500 mg was given for five days prophylactically. Follow-up was carried out one and six weeks after the day of operation. Data were processed with an IBM-compatible PC, using version 3.0 SPSS program. Students t-test, chi-square test and relative risk (95% confidence limit (CL)) were used for statistical analysis. Both groups were comparable in terms of age, parity, body weight, and body height. The duration of operation in the field was somewhat longer than that in the hospital, i.e. 24.58 vs 21.14 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Frequency of and predictors for withholding patient safety concerns among oncology staff: a survey study.

    Science.gov (United States)

    Schwappach, D L B; Gehring, K

    2015-05-01

    Speaking up about patient safety is vital to avoid errors reaching the patient and to improve a culture of safety. This study investigated the prevalence of non-speaking up despite concerns for safety and aimed to identify predictors for withholding voice among healthcare professionals (HCPs) in oncology. A self-administered questionnaire assessed safety concerns, speaking up beliefs and behaviours among nurses and doctors from nine oncology departments. Multiple regression analysis was used to identify predictors for withholding safety concerns. A total of 1013 HCPs returned the completed survey (response rate 65%). Safety concerns were common among responders. Fifty-four per cent reported to recognise their colleagues making potentially harmful errors at least sometimes. A majority of responders reported at least some episodes of withholding concerns about patient safety. Thirty-seven per cent said they remained silent at least once when they had information that might have helped prevent an incident. Respondents believed that a high level of interpersonal, communication and coping skills are necessary to speak up about patient safety issues at their workplace. Higher levels of perceived advocacy for patient safety and psychological safety significantly decreased the frequency of withholding voice. Remaining silent about safety concerns is a common phenomenon in oncology. Improved strategies are needed to support staff in effective communication and make cancer care safer. © 2014 John Wiley & Sons Ltd.

  18. Phase 1 dose-escalation trial evaluating the combination of the selective MET (mesenchymal-epithelial transition factor) inhibitor tivantinib (ARQ 197) plus erlotinib.

    Science.gov (United States)

    Goldman, Jonathan W; Laux, Isett; Chai, Feng; Savage, Ronald E; Ferrari, Dora; Garmey, Edward G; Just, Richard G; Rosen, Lee S

    2012-12-01

    Amplification of the mesenchymal-epithelial transition factor (MET) gene can promote tumor resistance to epidermal growth factor receptor (EGFR) inhibition. Dual EGFR-MET inhibition may overcome this resistance. Tivantinib (ARQ 197) is a selective, oral, non-ATP-competitive, small-molecule inhibitor of the MET receptor tyrosine kinase. This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of tivantinib combined with the EGFR inhibitor erlotinib. Patients with advanced solid malignancies were administered oral tivantinib at escalating doses of 120, 240, 360, and 480 mg twice daily (BID) plus 150 mg erlotinib once daily (QD). Single or multiple intrapatient dose escalation was planned in the absence of dose-limiting toxicity in the first cycle of therapy (21 days). Thirty-two patients received combination treatment. Tivantinib serum concentrations were not dose-proportional. The most common (≥ 20%) adverse events (AEs) regardless of causality included rash (n = 17), fatigue (n = 12), nausea (n = 10), abdominal pain (n = 10), diarrhea (n = 9), bradycardia (n = 9), and anemia (n = 7). AEs considered related to study treatment occurred in 28 patients (87.5%), and 5 patients (15.6%) had treatment-related serious AEs, including neutropenia, leukopenia, syncope, sinus bradycardia, and sick sinus syndrome. Fifteen of 32 patients (46.8%) had a partial response (n = 1) or stable disease (n = 14) as assessed by Response Evaluation Criteria in Solid Tumors. Six of 8 patients with nonsmall cell lung cancer achieved stable disease. The recommended phase 2 dose is tivantinib 360 mg BID plus erlotinib 150 mg QD. Tivantinib plus erlotinib was well tolerated with encouraging clinical activity, especially in patients with nonsmall cell lung cancer. Copyright © 2012 American Cancer Society.

  19. Automated Mixed Traffic Vehicle (AMTV) technology and safety study

    Science.gov (United States)

    Johnston, A. R.; Peng, T. K. C.; Vivian, H. C.; Wang, P. K.

    1978-01-01

    Technology and safety related to the implementation of an Automated Mixed Traffic Vehicle (AMTV) system are discussed. System concepts and technology status were reviewed and areas where further development is needed are identified. Failure and hazard modes were also analyzed and methods for prevention were suggested. The results presented are intended as a guide for further efforts in AMTV system design and technology development for both near term and long term applications. The AMTV systems discussed include a low speed system, and a hybrid system consisting of low speed sections and high speed sections operating in a semi-guideway. The safety analysis identified hazards that may arise in a properly functioning AMTV system, as well as hardware failure modes. Safety related failure modes were emphasized. A risk assessment was performed in order to create a priority order and significant hazards and failure modes were summarized. Corrective measures were proposed for each hazard.

  20. STUDY ON SAFETY TECHNOLOGY SCHEME OF THE UNMANNED HELICOPTER

    Directory of Open Access Journals (Sweden)

    Z. Lin

    2013-08-01

    Full Text Available Nowadays the unmanned helicopter is widely used for its' unique strongpoint, however, the high failure rate of unmanned helicopter seriously limits its further application and development. For solving the above problems, in this paper, the reasons for the high failure rate of unmanned helicopter is analyzed and the corresponding solution schemes are proposed. The main problem of the failure cause of the unmanned helicopter is the aircraft engine fault, and the failure cause of the unmanned helicopter is analyzed particularly. In order to improving the safety performance of unmanned helicopter system, the scheme of adding the safety parachute system to the unmanned helicopter system is proposed and introduced. These schemes provide the safety redundancy of the unmanned helicopter system and lay on basis for the unmanned helicopter applying into residential areas.

  1. A first-in-man study to evaluate the safety, tolerability, and pharmacokinetics of pasireotide (SOM230, a multireceptor-targeted somatostatin analog, in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Golor G

    2012-04-01

    Full Text Available Georg Golor1, Ke Hu2, Matthieu Ruffin3, Alexandra Buchelt3, Emmanuel Bouillaud3, Yanfeng Wang2, Mario Maldonado31Parexel International GmbH, Berlin, Germany; 2Novartis Pharmaceuticals, East Hanover, NJ, USA; 3Novartis Pharma AG, Basel, SwitzerlandAbstract: Pasireotide (SOM230 is a multireceptor-targeted somatostatin analog with high binding affinity for four of the five somatostatin receptor subtypes (sst1,2,3 and sst5, and potential clinical activity in several neuroendocrine and oncologic conditions, including acromegaly, Cushing’s disease, and neuroendocrine tumors (NET. This manuscript reports the first-in-man dose-escalation study of pasireotide, evaluating its safety, tolerability, and pharmacokinetics (PK in healthy male volunteers. A single dose of pasireotide 1–1200 µg was administered subcutaneously in four to eight subjects per dose level, with two additional subjects per cohort administered placebo. PK and safety evaluations were carried out over 7 days post-dose. Growth hormone (GH suppression was evaluated using a GH-releasing hormone stimulation test on Day –1 and Day 1 at 3–5 hours post-injection. Seventy-two subjects completed the study. Pasireotide was well tolerated with no serious adverse events observed at any dose. Transient elevations in blood glucose levels were observed 2–6 hours after administration of pasireotide at doses between 200 µg and 1200 µg, but this resolved without intervention by 23 hours post-dosing. The maximum tolerable dose was not established within the tested range. Pasireotide demonstrated a favorable PK profile with fast absorption (tmax: 0.25–0.5 hours, low clearance (CL/F: 8–13 L/hour, long effective elimination half-life (mean t½,ß: 7–11 hours, and a proportional dose-exposure relationship. GH suppression of 79%–96% was observed at single pasireotide doses between 200 µg and 1200 µg. In conclusion, pasireotide demonstrated favorable safety, tolerability, and PK profiles

  2. Successful pregnancy outcome in paroxysmal nocturnal hemoglobinuria (PNH following escalated eculizumab dosing to control breakthrough hemolysis

    Directory of Open Access Journals (Sweden)

    Ruby Sharma

    2015-01-01

    Full Text Available Pregnancy in women with paroxysmal nocturnal hemoglobinuria (PNH is associated with increased maternal and fetal morbidity and mortality. There is limited published experience regarding therapy of PNH during pregnancy. We describe a case of a 30 year old female with hypoplastic myelodysplastic syndrome and PNH. After two years of treatment with eculizumab, she became pregnant. She developed breakthrough hemolysis at 20 weeks gestation. Pharmacokinetic and pharmacodynamic studies demonstrated a subtherapeutic eculizumab level with absence of complement blockade. Escalation of her eculizumab dose successfully controlled hemolysis and restored therapeutic eculizumab level and activity. She delivered a healthy baby at 36 weeks.

  3. An exploratory study of safety culture, biological risk management and hand hygiene of healthcare professionals.

    Science.gov (United States)

    Bernard, Laurence; Biron, Alain; Lavigne, Geneviève; Frechette, Julie; Bernard, Agnès; Mitchell, Jonathan; Lavoie-Tremblay, Mélanie

    2017-11-08

    The objectives of the study were to: (1) examine the relationships between three different qualitative perceptions of safety culture and the Canadian Patient Safety Climate Survey factors; (2) determine whether these perceptions are associated with different hand hygiene practices. Healthcare-associated infections and safety cultures are a worldwide issue. During the A/H1N1 Influenza pandemic, Europe and North America did not have the same responses. Importantly, healthcare professionals' perceptions can influence patient safety through infection prevention practices like hand hygiene. A cross-sectional design was used with data collected in 2015. The Canadian Patient Safety Culture Survey and hand hygiene observations were gathered from three healthcare centres (two Canadian and one European). Descriptive analyses and ANOVAs were conducted to explore healthcare professionals' safety perceptions and practices. The rates of hand hygiene practices varied widely between the three sites, ranging from 35-77%. One site (Site 3) was found to have the highest scores of management follow-up, feedback about incidents, supervisory leadership for safety, unit learning culture and senior leadership support for safety, and the highest levels of overall patient safety grades for the unit and organization. The quantitative results of this study support the previously described model based on qualitative results: individual culture, blaming culture and collaborative culture. Differences between continents emerged regarding infection prevention practices and the way we qualify infections. The results raise concerns about infection practices and about safety cultures and challenges worldwide. © 2017 John Wiley & Sons Ltd.

  4. Recruitment of hospitals for a safety climate study: facilitators and barriers.

    Science.gov (United States)

    Rosen, Amy K; Gaba, David M; Meterko, Mark; Shokeen, Priti; Singer, Sara; Zhao, Shibei; Labonte, Alan; Falwell, Alyson

    2008-05-01

    Despite increasing emphasis on safety culture assessment, little is known about the factors that affect hospitals' participation in such studies. Factors affecting recruitment of 30 Department of Veterans Affairs (VA) hospitals into a study to evaluate perceptions of safety culture, or safety "climate," were examined. To minimize selection bias, hospitals were recruited that represented the spectrum of safety performance on the basis of Patient Safety Indicator scores. Invitations and additional mailings, informational conference calls, and personal contact with hospitals were used to encourage participation. Investigators worked closely with hospitals' key stakeholders to obtain support and buy-in for the study. Relationships among safety performance, organizational culture, and other hospital characteristics with hospitals' participation and ease of recruitment were examined. Findings were compared with those of a companion study in the non-VA setting. Despite attempts to optimize recruitment, it was necessary to contact more than 90 hospitals to obtain a 30-hospital sample. Having a more entrepreneurial culture (associated with risk-taking, innovation, and quality improvement) was significantly related to shorter recruitment time in VA and non-VA settings. Safety performance was significantly related to participation in the VA (that is, "better-performing" hospitals were more likely to be recruited than "lower-performing" hospitals), but not in the non-VA study, where recruitment was based on size and region. Researchers should recruit representative samples of hospitals based on measures of safety performance. Hospital selection bias could lead to erroneous findings, ultimately impeding efforts to improve safety within organizations.

  5. A randomized, double-blind, phase 2 study evaluating the safety and efficacy of AMG 416 for the treatment of secondary hyperparathyroidism in hemodialysis patients.

    Science.gov (United States)

    Bell, Gregory; Huang, Saling; Martin, Kevin J; Block, Geoffrey A

    2015-05-01

    Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease. We evaluated AMG 416, a long-acting peptide agonist of the calcium-sensing receptor, to assess its safety, tolerability, and efficacy and to determine a safe and effective starting dose for subsequent phase 2 studies. The study was not designed to titrate AMG 416 dosing to achieve a specific PTH treatment goal. This is a multicenter, double-blind, randomized, placebo-controlled, dose-escalation study designed to evaluate the safety and efficacy of AMG 416 administered thrice weekly by IV bolus at the end of hemodialysis for up to 4 weeks. Eligible subjects were enrolled in one of three cohorts and treated with 5 mg of AMG 416 or placebo for 2 weeks (Cohort 1) or 5 or 10 mg of AMG 416 or placebo for 4 weeks (Cohorts 2 and 3). The primary endpoint was mean percentage change from baseline in PTH during the efficacy assessment phase (EAP) in Cohorts 2 and 3. Analysis of the primary endpoint showed that treatment with AMG 416 at 10 mg (Cohort 2) and 5 mg (Cohort 3) for up to 4 weeks resulted in mean 49.4% and 33.0% reductions from baseline in PTH during the efficacy assessment phase, respectively (p AMG 416 achieved PTH ≤300 pg/mL and ≥30% reduction in PTH from baseline in both cohorts. The observed decreases in serum-corrected calcium were well tolerated and serum phosphate levels also tended to decrease. The present clinical findings support the continued development of AMG 416 as a treatment for SHPT in hemodialysis patients.

  6. Study of fast reactor safety test facilities. Preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Bell, G.I.; Boudreau, J.E.; McLaughlin, T.; Palmer, R.G.; Starkovich, V.; Stein, W.E.; Stevenson, M.G.; Yarnell, Y.L.

    1975-05-01

    Included are sections dealing with the following topics: (1) perspective and philosophy of fast reactor safety analysis; (2) status of accident analysis and experimental needs; (3) experiment and facility definitions; (4) existing in-pile facilities; (5) new facility options; and (6) data acquisition methods. (DG)

  7. Applying an ecological restoration approach to study patient safety culture in an intensive care unit.

    Science.gov (United States)

    Gimenes, Fernanda Raphael Escobar; Torrieri, Mayara Carvalho Godinho Rigobello; Gabriel, Carmen Silvia; Rocha, Fernanda Ludmilla Rossi; Silva, Ana Elisa Bauer de Camargo; Shasanmi, Rebecca O; Cassiani, Silvia Helena De Bortoli

    2016-04-01

    To gain an understanding of medication safety culture and other quality issues in a Brazilian intensive care unit using a restorative approach. Patient safety should be considered one of the pillars of quality in health care. Thus, patient safety culture is increasingly being explored as a guide for quality improvement efforts. A qualitative approach. Participatory photographic research methods from the field of ecological restoration were adapted in this study. This study used focus groups, then subsequent nurse-led photo-narrated walkabouts, and photo elicitation with 23 nurses and one physician in interactive phases of data collection and analysis over an eight-month timeframe. The core themes identified were: the 'medication system shapes patient safety' and the 'feeling of helplessness in the face of the prevailing organization culture'. Participants discussed supports exiting in the intensive care unit that shape medication safety, the barriers that impede safe medication management, the solutions to improve medication safety and the creation of a better medication safety culture. The methods used allowed participants to visualise sound practices as well as key safety issues, reflect on their day-to-day work, re-think potential improvements, and enact changes to improve medication safety and medication safety culture. However, the patient safety culture is also marked by administrative pressure. The hospital needs to adopt participatory management, where the health professionals can act together with the organisational leaders to promote a just culture. The participatory photographic research methods from the field of ecological restoration provided participants with a tool to promote patient safety culture and engage policy change dialogue. However, it will be important in future restorative research to track-specific safety outcomes over time to assess the cost-benefit of the adoption of participatory management models. © 2016 John Wiley & Sons Ltd.

  8. The tumor-targeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer.

    Science.gov (United States)

    Catania, Chiara; Maur, Michela; Berardi, Rossana; Rocca, Andrea; Giacomo, Anna Maria Di; Spitaleri, Gianluca; Masini, Cristina; Pierantoni, Chiara; González-Iglesias, Reinerio; Zigon, Giulia; Tasciotti, Annaelisa; Giovannoni, Leonardo; Lovato, Valeria; Elia, Giuliano; Menssen, Hans D; Neri, Dario; Cascinu, Stefano; Conte, Pier Franco; Braud, Filippo de

    2015-01-01

    A phase Ib/II trial was performed to evaluate safety, tolerability, recommended dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion protein, in combination with doxorubicin in patients with solid tumors (phase Ib) and metastatic breast cancer (phase II). Six patient cohorts with progressive solid tumors (n = 19) received escalating doses of F16-IL2 [5-25 Million International Units (MIU) of IL2 equivalent dose] in combination with escalating doses of doxorubicin (0-25 mg/m(2)) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n = 10) received the drug combination at the RD. Clinical data and laboratory findings were analyzed for safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU, in combination with the RD of doxorubicin (25 mg/m(2)). No human anti-fusion protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours for cohorts dosed at lower and higher levels, respectively. Toxicities were controllable and reversible, with no combination treatment-related death. After 8 weeks, 57% and 67% disease control rates were observed for Phase I and II, respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9 patients evaluable for efficacy. One patient experienced a long lasting partial response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and repeatedly administered at the RD of 25 MIU in combination with 25 mg/m(2) doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.

  9. Predictors of effective de-escalation in acute inpatient psychiatric settings.

    Science.gov (United States)

    Lavelle, Mary; Stewart, Duncan; James, Karen; Richardson, Michelle; Renwick, Laoise; Brennan, Geoffrey; Bowers, Len

    2016-08-01

    To explore the factors that influence the use of de-escalation and its success in halting conflict in acute psychiatric inpatient setting. De-escalation is the use of verbal and nonverbal communication to reduce or eliminate aggression and violence during the escalation phase of a patient's behaviour. Although de-escalation is a first-line intervention in aggression management in acute psychiatric settings, little is known about the use or effectiveness of this technique. A retrospective case note analysis. For each patient (n = 522), their involvement in conflict (e.g. aggression) or containment (e.g. coerced medication) during the first two weeks of their admission was recorded. The frequency and order of the conflict and containment events were identified during each shift. The sequences of events occurring in shifts involving de-escalation were analysed. Sequences where de-escalation ended the pattern of conflict or containment were categorised as 'successful', and all others were categorised as 'unsuccessful'. Over half of patients (53%) experienced de-escalation during the first two weeks of admission, with the majority of these (37%) experiencing multiple episodes. De-escalation was successful in approximately 60% of cases. Successful de-escalations were preceded by fewer, and less aggressive, conflict events, compared with unsuccessful de-escalations, which were most frequently followed by administration of pro re nata medication. Patients with a history of violence were more likely to experience de-escalation, and it was more likely to be unsuccessful. De-escalation is frequently effective in halting a sequence of conflict in acute inpatient settings, but patients with a history of violence may be specifically challenging. These findings provide support for de-escalation in practice but suggest that nurses may lack confidence in using the technique when the risk of violence is greater. Providing evidence-based staff training may improve staff confidence

  10. Review of light--water reactor safety studies. Volume 3 of health and safety impacts of nuclear, geothermal, and fossil-fuel electric generation in California

    Energy Technology Data Exchange (ETDEWEB)

    Nero, A.V.; Farnaam, M.R.K.

    1977-01-01

    This report summarizes and compares important studies of light-water nuclear reactor safety, emphasizing the Nuclear Regulatory Commission's Reactor Safety Study, work on risk assessment funded by the Electric Power Research Institute, and the Report of the American Physical Society study group on light-water reactor safety. These reports treat risk assessment for nuclear power plants and provide an introduction to the basic issues in reactor safety and the needs of the reactor safety research program. Earlier studies are treated more briefly. The report includes comments on the Reactor Safety Study. The manner in which these studies may be used and alterations which would increase their utility are discussed.

  11. Study on Analysis and Countermeasure of China's Legal System of Food Safety and Hygiene

    OpenAIRE

    Yongyong Zhu

    2013-01-01

    The aim of study is to solve the food safety problems existing in the real life, ensuring the food health safety, based on the “ Food Hygiene Law of the People's Republic of China” promulgated in 1995 by China, starting from the aspects such as production, marketing, regulatory to the integrate the standards of edible farm product quality safety standards, food hygiene standards, food quality standards and relevant food industry mandatory standards, establishing scientific and standardized fo...

  12. Safety studies of aluminum in vaccines lack immunotoxicity analysis of this immunological adjuvant: Ignorance or deception?

    OpenAIRE

    Arumugham, Vinu

    2017-01-01

    The safety studies most often referred by vaccine regulators when making claims about the safety of aluminum in vaccines, have ignored the immunotoxicity of aluminum. Vaccinologists admit that they neither understand the general immunological mechanisms involved in vaccination nor do they understand the mechanisms involved in aluminum adjuvant action. Thus vaccine regulators have no scientific basis to make vaccine safety claims. Given this situation one would expect that vaccine regu...

  13. Safety, Tolerability, Systemic Exposure, and Metabolism of CRS3123, a Methionyl-tRNA Synthetase Inhibitor Developed for Treatment of Clostridium difficile, in a Phase 1 Study.

    Science.gov (United States)

    Nayak, Seema U; Griffiss, J McLeod; Blumer, Jeffrey; O'Riordan, Mary Ann; Gray, Wesley; McKenzie, Robin; Jurao, Robert A; An, Amanda T; Le, Melissa; Bell, Stacie J; Ochsner, Urs A; Jarvis, Thale C; Janjic, Nebojsa; Zenilman, Jonathan M

    2017-08-01

    Clostridium difficile causes antibiotic-associated diarrhea and is a major public health concern. Current therapies disrupt the protective intestinal flora, do not reliably prevent recurrent infections, and will be decreasingly effective should less susceptible strains emerge. CRS3123 is an oral agent that inhibits bacterial methionyl-tRNA synthetase and has potent activity against C. difficile and aerobic Gram-positive bacteria but little activity against Gram-negative bacteria, including anaerobes. This first-in-human, double-blind, placebo-controlled, dose escalation study evaluated the safety and systemic exposure of CRS3123 after a single oral dose in healthy adults. Five cohorts of eight subjects each received CRS3123 or placebo in a 3:1 ratio. Doses for the respective active arms were 100 mg, 200 mg, 400 mg, 800 mg, and 1,200 mg. Blood and urine were collected for pharmacokinetic analysis. CRS3123 concentrations were measured with validated LC-MS/MS techniques. There were no serious adverse events or immediate allergic reactions during administration of CRS3123. In the CRS3123-treated groups, the most frequent adverse events were decreased hemoglobin, headache, and abnormal urine analysis; all adverse events in the active-treatment groups were mild to moderate, and their frequency did not increase with dose. Although CRS3123 systemic exposure increased at higher doses, the increase was less than dose proportional. The absorbed drug was glucuronidated at reactive amino groups on the molecule, which precluded accurate pharmacokinetic analysis of the parent drug. Overall, CRS3123 was well tolerated over this wide range of doses. This safety profile supports further investigation of CRS3123 as a treatment for C. difficile infections. (This study has been registered at ClinicalTrials.gov under identifier NCT01551004.). Copyright © 2017 American Society for Microbiology.

  14. System and safety studies of accelerator driven transmutation systems

    Energy Technology Data Exchange (ETDEWEB)

    Gudowski, W.; Wallenius, J.; Tucek, K.; Eriksson, Marcus; Carlsson, Johan; Seltborg, P.; Cetnar, J. [Royal Inst. of Technology, Stockholm (Sweden). Dept. of Nuclear and Reactor Physics

    2001-05-01

    The research on safety of Accelerator-Driven Transmutation Systems (ADS) at the department has been focused on: a) ADS core design and development of advanced nuclear fuel optimised for high transmutation rates and good safety features; b) analysis of ADS-dynamics c) computer code and nuclear data development relevant for simulation and optimization of ADS; d) participation in ADS experiments including 1 MW spallation target manufacturing, subcritical experiments MUSE (CEA-Cadarache). Moreover, during the reporting period the EU-project 'IABAT', co-ordinated by the department has been finished and 4 other projects have been initiated in the frame of the 5th European Framework Programme. Most of the research topics reported in this paper are referred to appendices, which have been published in the open literature. The topics, which are not yet published, are described here in more details.

  15. En Route Patient Safety: A Mixed-Methods Study

    Science.gov (United States)

    2014-03-01

    and CASF member’s rear repeatedly bumped pts legs during litter carry to acft [aircraft] causing pt obvious pain as displayed by facial grimace...mislabeled medications were common issues that could place a patient’s safety in jeopardy. Patients arrive to plane, many needed pain medications...Your endorphins are working. You push through a lot of stuff that you would generally go to sleep. But we know this mission is that important

  16. The First Study of Patient Safety Culture in Iranian Primary Health Centers

    Directory of Open Access Journals (Sweden)

    Mojtaba Sedaghat

    2012-07-01

    Full Text Available Although the error in health care has received attention recently, patient safety culture in health centers has been relatively neglected. To measure the patient safety culture in primary health centers. A cross-sectional study, utilizing the modified version of the Hospital Survey on Patient Safety Culture (HSOPSC developed by the Agency for Healthcare Research and Quality (AHRQ and a demographic questionnaire. Healthcare staffs from health centers were participated in the survey. The patient safety culture score including subscores on 11 dimensions and 39 items; patient safety grade and number of events reported. The overall positive response rate of patient safety culture was 57 ±16.8 (CI 9555%-59%. The dimensions that received higher positive response rate were "Teamwork across units of health center", "Teamwork within units", "Head of center support for patient safety". The lowest percentage of positive responses was "Non punitive response to error". There were no relationship between working years and patients safely culture score. Similarly, no relationship was found between professional, gender and total patients safely culture score. Statistical analysis showed discrepancies between Iranian health centers and the US hospitals in three dimensions. For improving patient safety culture in health centers, it is necessary to have enough staff and establish an environment to be open and fair with staff which helps report errors spontaneously and without any fear. The findings of this study could be used to measure changes in patient safety culture over the time.

  17. The first study of patient safety culture in Iranian primary health centers.

    Science.gov (United States)

    Tabrizchi, Narges; Sedaghat, Mojtaba

    2012-01-01

    Although the error in health care has received attention recently, patient safety culture in health centers has been relatively neglected. To measure the patient safety culture in primary health centers. A cross-sectional study, utilizing the modified version of the Hospital Survey on Patient Safety Culture (HSOPSC) developed by the Agency for Healthcare Research and Quality (AHRQ) and a demographic questionnaire. Healthcare staffs from health centers were participated in the survey. The patient safety culture score including subscores on 11 dimensions and 39 items; patient safety grade and number of events reported. The overall positive response rate of patient safety culture was 57 ± 16.8 (CI (95)55%-59%). The dimensions that received higher positive response rate were "Teamwork across units of health center", "Teamwork within units", "Head of center support for patient safety". The lowest percentage of positive responses was "Non punitive response to error". There were no relationship between working years and patients safely culture score. Similarly, no relationship was found between professional, gender and total patients safely culture score. Statistical analysis showed discrepancies between Iranian health centers and the US hospitals in three dimensions. For improving patient safety culture in health centers, it is necessary to have enough staff and establish an environment to be open and fair with staff which helps report errors spontaneously and without any fear. The findings of this study could be used to measure changes in patient safety culture over the time.

  18. Patient safety improvement programmes for primary care. Review of a Delphi procedure and pilot studies by the LINNEAUS collaboration on patient safety in primary care

    Science.gov (United States)

    Verstappen, Wim; Gaal, Sander; Esmail, Aneez; Wensing, Michel

    2015-01-01

    ABSTRACT Background: To improve patient safety it is necessary to identify the causes of patient safety incidents, devise solutions and measure the (cost-) effectiveness of improvement efforts. Objective: This paper provides a broad overview with practical guidance on how to improve patient safety. Methods: We used modified online Delphi procedures to reach consensus on methods to improve patient safety and to identify important features of patient safety management in primary care. Two pilot studies were carried out to assess the value of prospective risk analysis (PRA), as a means of identifying the causes of a patient safety incident. Results: A range of different methods can be used to improve patient safety but they have to be contextually specific. Practice organization, culture, diagnostic errors and medication safety were found to be important domains for further improvement. Improvement strategies for patient safety could benefit from insights gained from research on implementation of evidence-based practice. Patient involvement and prospective risk analysis are two promising and innovative strategies for improving patient safety in primary care. Conclusion: A range of methods is available to improve patient safety, but there is no ‘magic bullet.’ Besides better use of the available methods, it is important to use new and potentially more effective strategies, such as prospective risk analysis. PMID:26339837

  19. Physical discipline, escalation, and child abuse potential: psychometric evidence for the Analog Parenting Task.

    Science.gov (United States)

    Russa, Mary Bower; Rodriguez, Christina M

    2010-01-01

    Data from three studies provide new evidence to support the validity of the Analog Parenting Task (APT) as an instrument to assess risk for harsh, physically aggressive parenting. In this series of studies, there was a strong association between APT scores of expected use and escalation of discipline strategies and self-reported disciplinary attitudes. APT scores were also associated with physical abuse potential as assessed by both a well-established measure of child abuse potential (Child Abuse Potential Inventory) and another instrument designed specifically for use in pre-parent populations (e.g., Adult-Adolescent Parenting Inventory-2). This study provides new psychometric evidence to support the use of the APT to assess harsh parenting. Additionally, these data highlight the connection between acceptance and use of physical disciplinary strategies, propensity for disciplinary escalation, and risk for abuse perpetration. The findings are discussed in the context of Milner's Social Information Processing model [Milner, 2003] of abuse, which suggests that parental selection of disciplinary responding and the monitoring of disciplinary responding are key events in the disciplinary process. The APT may prove a useful adjunct to more commonly used self-report measures to allow for multimethod assessment of risk for punitive parenting.

  20. EFFECT OF TARIFF ESCALATION ON GHANAIAN COCOA EXPORTS: AN EMPIRICAL PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Ahmed Abdul Aziz

    2017-01-01

    Full Text Available This study analyses the effects of tariff escalation on Ghanaian cocoa exports in four importing markets: USA, EU, Japan and Malaysia. The study estimates nominal and effective protection coefficients in these markets based on ad-valorem equivalent of applied and bound specific tariffs. Results revealed that, effective protection exists in the Japanese and Malaysian cocoa industries at different stages of processing on both bound and applied tariffs. In contrast, the USA and the EU do not effectively protect their cocoa industries, thus, no tariff escalation on applied tariffs against cocoa imports from Ghana. This study concludes that from a static effect, higher tariffs do have a negative consequence on Ghanaian cocoa exports in these importing countries. From a dynamic perspective however, the relationship between tariff structures in these importing countries and Ghanaian cocoa exports is somewhat ambiguous and each situation has to be viewed on their own merit. A complete elimination of tariffs as a form of trade barrier on Ghanaian cocoa exports does not necessarily imply that Ghana could easily increase its exports of value added cocoa.

  1. Nuclear Weapons and Coercive Escalation in Regional Conflicts: Lessons from North Korea and Pakistan

    Science.gov (United States)

    2014-11-01

    Daniel S. Geller . “Nuclear Weapons, Deterrence and Crisis Escalation.” Journal of Conflict Resolution 34 (1990). 17 “Nuclear Weapons, Deterrence... Geller , “Nuclear Weapons, Deterrence and Crisis Escalation,” 1990. 21 Beardsley and Asal, “Winning with the Bomb,” 2009. 22 Utgoff and Wheeler...After Proliferation: Deterrence Theory and Emerging Nuclear Powers,” 2012, 18. 25 Geller , “Nuclear Weapons, Deterrence and Crisis Escalation,” 1990

  2. Studying Patient Safety Culture from the Viewpoint of Nurse in educational hospitals Ilam City

    Directory of Open Access Journals (Sweden)

    Milad Borji

    2016-12-01

    Full Text Available Introduction: Patient safety culture is the first necessary step to reduce medical errors and improve patient's condition. In this context, this article aims at studying the condition of patient safety culture in hospitals in Elam in 2016. Materials and Methods: In this cross-sectional study, 150 nurses in Ilam were randomly selected. The Culture Hospital Survey on Patient Safety (HSOPSC was used and its reliability and validity had been confirmed by the previous studies. The data were analyzed by SPSS17. Results: The results showed that the nurses' safety was at positive(62.37± 8.70 and there could be found no significant difference in patient safety among the studied hospitals in this article (P<.05. Extra-organizational teamwork and non-punitive response, among the aspects of patient safety, had the lowest means and organizational learning and general understanding had the highest. Conclusion: Considering the importance of patient safety, the interventions need to be performed in order to improve the patient safety condition among nurses, especially in two aspects of extra-organizational teamwork and non-punitive response that had the lowest means.

  3. Investor’s Commitment Bias and Escalation of Firm’s Investment Decision

    Directory of Open Access Journals (Sweden)

    Anis JARBOUI

    2012-12-01

    Full Text Available This study examines the reasons of perseverance in firm’s investment decision. It shows the possible influence of three closely related features which are: firm’s financial indicators, investor’s risk profile, and investor’s commitment bias, on a firm’s investment decisions escalation. This study aims to provide evidence as to whether investor considers the financial and risk’s perception features (financial strength and risk profile to persevere his initial investment decision while he notes a high level of commitment bias. The proposed model of this paper uses GLM univariate data analyses to examine this relationship. Investor’s risk profile and his commitment bias have been measured by means of a questionnaire comprising several items. As for the selected sample, it has been composed of some 360 Tunisian individual investors. Our results have revealed that investors pay more attention to keep their psychology comfort than their financial comfort. It exposed the importance of the investor’s commitment bias and its risk perception in explaining investment decision escalation. Moreover results shows that there is strong and significant empirical relationship linking the escalatory behavior in investment decision and the interaction effects between the three independent variables. This means that, in practice, investors consider the three factors simultaneously.

  4. A Study on the Construct Validity of Safety Culture Oversight Model for Nuclear Power Operating Organization

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Choi, Young Sung; Oh, Jang Jin [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2015-05-15

    In Korea, the safety policy statement declared in 1994 by government stressed the importance of safety culture and licensees were encouraged to manage and conduct their self-assessments. A change in regulatory position about safety culture oversight was made after the event of SBO cover-up in Kori unit 1 and several subsequent falsification events. Since then KINS has been developing licensee's safety culture oversight system including conceptual framework of oversight, prime focus area for oversight, and specific details on regulatory expectations, all of which are based on defence-in-depth (DiD) safety enhancement approach. Development and gathering of performance data which is related to actual 'safety' of nuclear power plant are needed to identify the relationship between safety culture and safety performance. Authors consider this study as pilot which has a contribution on verifying the construct validity of the model and the effectiveness of survey based research. This is the first attempt that the validity of safety culture oversight model has been investigated with empirical data obtained from Korean nuclear power operating organization.

  5. Changes in patient safety culture after restructuring of intensive care units: Two cross-sectional studies.

    Science.gov (United States)

    Vifladt, Anne; Simonsen, Bjoerg O; Lydersen, Stian; Farup, Per G

    2016-02-01

    Compare changes in registered nurses' perception of the patient safety culture in restructured and not restructured intensive care units during a four-year period. Two cross-sectional surveys were performed, in 2008/2009 (time 1) and 2012/2013 (time 2). During a period of 0-3 years after time 1, three of six hospitals merged their general and medical intensive care units (restructured). The other hospitals maintained their structure of the intensive care units (not restructured). Intensive care units in hospitals at one Norwegian hospital trust. The safety culture was measured with Hospital Survey on Patient Safety Culture. At times 1 and 2, 217/302 (72%) and 145/289 (50%) registered nurses participated. Restructuring was negatively associated with change in the safety culture, in particular, the dimensions of the safety culture within the unit level. The dimensions most vulnerable for restructuring were manager expectations and actions promoting safety, teamwork within hospital units and staffing. In this study, the restructuring of intensive care units was associated with a negative impact on the safety culture. When restructuring, the management should be particularly aware of changes in the safety culture dimensions manager expectations and actions promoting safety, teamwork within hospital units and staffing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics.

    Science.gov (United States)

    Antonik, Laurie J; Goldwater, D Ronald; Kilpatrick, Gavin J; Tilbrook, Gary S; Borkett, Keith M

    2012-08-01

    A new benzodiazepine, remimazolam, metabolized by tissue esterases to an inactive compound, CNS 7054, has been developed to permit a fast onset, a short and more predictable duration of sedative action, and a more rapid recovery profile than with currently available benzodiazepines. We report on the safety and efficacy of the first human study. A phase I, single-center, double-blind, placebo- and active-controlled, randomized, single-dose escalation study was conducted. Up to 10 cohorts of healthy subjects were scheduled to receive a single 1-minute IV infusion of remimazolam, midazolam, or placebo. In the 10 possible cohorts, remimazolam doses were from 0.01 to 0.35 mg/kg. In cohorts 1 to 3, 6 subjects received remimazolam and 1 placebo. From cohort 4 onward, an additional 3 subjects in each cohort received midazolam (0.075 mg/kg). Safety, pharmacokinetics, and pharmacodynamics were measured. A stop criterion of loss of consciousness for >5 minutes in >50% of subjects was predefined. The stop criterion was reached in cohort 9 (0.30 mg/kg remimazolam) so that 81 subjects were enrolled. Remimazolam was well tolerated in all dose cohorts, and no serious adverse events (AEs) were reported. Three AEs of mild (Spo(2) 85%-88%) hemoglobin desaturation (2 in the remimazolam groups and 1 in the midazolam group) resolved spontaneously, and 1 AE of moderate hemoglobin desaturation (Spo(2) 75%) resolved with a chin lift in the highest remimazolam dose group. No supplemental oxygen or manual ventilation was required. Vital signs remained stable throughout, although there was an increase in heart rate 2 minutes postdose for both remimazolam and midazolam. There were no reports of hypo- or hypertension. The pharmacokinetic behavior of remimazolam was linear and its systemic clearance approximately 3 times that of midazolam. Clearance was essentially independent of body weight. A rapid onset and dose-dependent sedation was observed after administration of remimazolam at 0.05 mg

  7. Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies

    Directory of Open Access Journals (Sweden)

    A. Anil Sinaci

    2015-01-01

    Full Text Available Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases.

  8. On the safety of aircraft systems: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Guridi, G.; Hall, R.E.; Fullwood, R.R.

    1997-05-14

    An airplane is a highly engineered system incorporating control- and feedback-loops which often, and realistically, are non-linear because the equations describing such feedback contain products of state variables, trigonometric or square-root functions, or other types of non-linear terms. The feedback provided by the pilot (crew) of the airplane also is typically non-linear because it has the same mathematical characteristics. An airplane is designed with systems to prevent and mitigate undesired events. If an undesired triggering event occurs, an accident may process in different ways depending on the effectiveness of such systems. In addition, the progression of some accidents requires that the operating crew take corrective action(s), which may modify the configuration of some systems. The safety assessment of an aircraft system typically is carried out using ARP (Aerospace Recommended Practice) 4761 (SAE, 1995) methods, such as Fault Tree Analysis (FTA) and Failure Mode and Effects Analysis (FMEA). Such methods may be called static because they model an aircraft system on its nominal configuration during a mission time, but they do not incorporate the action(s) taken by the operating crew, nor the dynamic behavior (non-linearities) of the system (airplane) as a function of time. Probabilistic Safety Assessment (PSA), also known as Probabilistic Risk Assessment (PRA), has been applied to highly engineered systems, such as aircraft and nuclear power plants. PSA encompasses a wide variety of methods, including event tree analysis (ETA), FTA, and common-cause analysis, among others. PSA should not be confused with ARP 4761`s proposed PSSA (Preliminary System Safety Assessment); as its name implies, PSSA is a preliminary assessment at the system level consisting of FTA and FMEA.

  9. Prospective evaluation of a hydrogel spacer for rectal separation in dose-escalated intensity-modulated radiotherapy for clinically localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Eckert Franziska

    2013-01-01

    Full Text Available Abstract Background As dose-escalation in prostate cancer radiotherapy improves cure rates, a major concern is rectal toxicity. We prospectively assessed an innovative approach of hydrogel injection between prostate and rectum to reduce the radiation dose to the rectum and thus side effects in dose-escalated prostate radiotherapy. Methods Acute toxicity and planning parameters were prospectively evaluated in patients with T1-2 N0 M0 prostate cancer receiving dose-escalated radiotherapy after injection of a hydrogel spacer. Before and after hydrogel injection, we performed MRI scans for anatomical assessment of rectal separation. Radiotherapy was planned and administered to 78 Gy in 39 fractions. Results From eleven patients scheduled for spacer injection the procedure could be performed in ten. In one patient hydrodissection of the Denonvillier space was not possible. Radiation treatment planning showed low rectal doses despite dose-escalation to the target. In accordance with this, acute rectal toxicity was mild without grade 2 events and there was complete resolution within four to twelve weeks. Conclusions This prospective study suggests that hydrogel injection is feasible and may prevent rectal toxicity in dose-escalated radiotherapy of prostate cancer. Further evaluation is necessary including the definition of patients who might benefit from this approach. Trial registration: German Clinical Trials Register DRKS00003273.

  10. System Study: High-Pressure Safety Injection 1998-2014

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, John Alton [Idaho National Lab. (INL), Idaho Falls, ID (United States). Risk Assessment and Management Services Dept.

    2015-12-01

    This report presents an unreliability evaluation of the high-pressure safety injection system (HPSI) at 69 U.S. commercial nuclear power plants. Demand, run hours, and failure data from fiscal year 1998 through 2014 for selected components were obtained from the Institute of Nuclear Power Operations (INPO) Consolidated Events Database (ICES). The unreliability results are trended for the most recent 10 year period, while yearly estimates for system unreliability are provided for the entire active period. No statistically significant increasing or decreasing trends were identified in the HPSI results.

  11. System Study: High-Pressure Safety Injection 1998–2013

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, John Alton [Idaho National Lab. (INL), Idaho Falls, ID (United States). Risk Assessment and Management Services Dept.

    2015-02-01

    This report presents an unreliability evaluation of the high-pressure safety injection system (HPSI) at 69 U.S. commercial nuclear power plants. Demand, run hours, and failure data from fiscal year 1998 through 2013 for selected components were obtained from the Institute of Nuclear Power Operations (INPO) Consolidated Events Database (ICES). The unreliability results are trended for the most recent 10-year period while yearly estimates for system unreliability are provided for the entire active period. No statistically significant increasing or decreasing trends were identified in the HPSI results.

  12. System Study: High-Pressure Safety Injection 1998–2012

    Energy Technology Data Exchange (ETDEWEB)

    T. E. Wierman

    2013-10-01

    This report presents an unreliability evaluation of the high-pressure safety injection system (HPSI) at 69 U.S. commercial nuclear power plants. Demand, run hours, and failure data from fiscal year 1998 through 2012 for selected components were obtained from the Equipment Performance and Information Exchange (EPIX). The unreliability results are trended for the most recent 10 year period while yearly estimates for system unreliability are provided for the entire active period. No statistically significant increasing or decreasing trends were identified in the HPSI results.

  13. Safety culture assessment in petrochemical industry: a comparative study of two algerian plants.

    Science.gov (United States)

    Boughaba, Assia; Hassane, Chabane; Roukia, Ouddai

    2014-06-01

    To elucidate the relationship between safety culture maturity and safety performance of a particular company. To identify the factors that contribute to a safety culture, a survey questionnaire was created based mainly on the studies of Fernández-Muñiz et al. The survey was randomly distributed to 1000 employees of two oil companies and realized a rate of valid answer of 51%. Minitab 16 software was used and diverse tests, including the descriptive statistical analysis, factor analysis, reliability analysis, mean analysis, and correlation, were used for the analysis of data. Ten factors were extracted using the analysis of factor to represent safety culture and safety performance. The results of this study showed that the managers' commitment, training, incentives, communication, and employee involvement are the priority domains on which it is necessary to stress the effort of improvement, where they had all the descriptive average values lower than 3.0 at the level of Company B. Furthermore, the results also showed that the safety culture influences the safety performance of the company. Therefore, Company A with a good safety culture (the descriptive average values more than 4.0), is more successful than Company B in terms of accident rates. The comparison between the two petrochemical plants of the group Sonatrach confirms these results in which Company A, the managers of which are English and Norwegian, distinguishes itself by the maturity of their safety culture has significantly higher evaluations than the company B, who is constituted of Algerian staff, in terms of safety management practices and safety performance.

  14. Safety Culture Assessment in Petrochemical Industry: A Comparative Study of Two Algerian Plants

    Science.gov (United States)

    Boughaba, Assia; Hassane, Chabane; Roukia, Ouddai

    2014-01-01

    Background To elucidate the relationship between safety culture maturity and safety performance of a particular company. Methods To identify the factors that contribute to a safety culture, a survey questionnaire was created based mainly on the studies of Fernández-Muñiz et al. The survey was randomly distributed to 1000 employees of two oil companies and realized a rate of valid answer of 51%. Minitab 16 software was used and diverse tests, including the descriptive statistical analysis, factor analysis, reliability analysis, mean analysis, and correlation, were used for the analysis of data. Ten factors were extracted using the analysis of factor to represent safety culture and safety performance. Results The results of this study showed that the managers' commitment, training, incentives, communication, and employee involvement are the priority domains on which it is necessary to stress the effort of improvement, where they had all the descriptive average values lower than 3.0 at the level of Company B. Furthermore, the results also showed that the safety culture influences the safety performance of the company. Therefore, Company A with a good safety culture (the descriptive average values more than 4.0), is more successful than Company B in terms of accident rates. Conclusion The comparison between the two petrochemical plants of the group Sonatrach confirms these results in which Company A, the managers of which are English and Norwegian, distinguishes itself by the maturity of their safety culture has significantly higher evaluations than the company B, who is constituted of Algerian staff, in terms of safety management practices and safety performance. PMID:25180135

  15. Cluster randomized, controlled trial on patient safety improvement in general practice: a study protocol

    Science.gov (United States)

    2013-01-01

    Background An open, constructive safety culture is key in healthcare since it is seen as a main condition for patient safety. Studies have examined culture improvement strategies in hospitals. In primary care, however, not much is known about effective strategies to improve the safety culture yet. The purpose of this study is to examine the effect of two patient safety culture interventions: a patient safety culture questionnaire solely, the SCOPE, or the SCOPE questionnaire combined with a patient safety workshop. The purpose of this paper is to describe the rationale and design of this trial. Methods/design The SCOPE Intervention Study is a cluster randomized, three-armed controlled trial, that will be conducted in 30 general practices in the Netherlands. Ten practices in the first intervention arm will complete the SCOPE questionnaire and are expected to draw and implement their own improvement initiatives based on a computerised feedback report. In the second intervention arm, staff of the ten practices also will be asked to complete the SCOPE questionnaire and in addition will be given a complementary workshop. This workshop is theoretical and interactive, educating staff and facilitating discussion, leading to a practice specific action plan for patient safety improvement. The results of the SCOPE questionnaire are incorporated in the workshop. The ten practices in the control arm continue care as usual. Baseline and follow-up measurements will be conducted with an implementation period of one year. The primary outcome will include the number of incidents reported and secondary several quality and safety indicators and the patient safety culture. Moreover, interviews will be conducted at follow-up to evaluate the implementation process of the intervention. Discussion Results of this study will give insight in the effect of administering a culture questionnaire or the questionnaire with a complementary workshop. This knowledge will aid implementation of

  16. Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

    Energy Technology Data Exchange (ETDEWEB)

    Brower, Jeffrey V. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Chen, Shuai [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Bassetti, Michael F. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Yu, Menggang [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Harari, Paul M.; Ritter, Mark A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States); Baschnagel, Andrew M., E-mail: baschnagel@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin (United States)

    2016-12-01

    the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.

  17. Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS – A Novel Therapeutic Opportunity

    Science.gov (United States)

    Winstedt, Lena; Järnum, Sofia; Nordahl, Emma Andersson; Olsson, Andreas; Runström, Anna; Bockermann, Robert; Karlsson, Christofer; Malmström, Johan; Palmgren, Gabriella Samuelsson; Malmqvist, Ulf; Björck, Lars; Kjellman, Christian

    2015-01-01

    IdeS is a streptococcal protease that cleaves IgG antibodies into F(ab’)2 and Fc fragments with a unique degree of specificity, thereby providing a novel treatment opportunity of IgG-driven autoimmune conditions and antibody mediated transplant rejection. Here we report the results from a first in man, double blinded and randomized study with single ascending doses of IdeS in healthy, male subjects. Twenty healthy subjects were given intravenous single ascending doses of IdeS. With impressive efficacy IdeS cleaved the entire plasma IgG-pool only minutes after dosing. IgG reached nadir 6-24 hours after dosing and then slowly recovered. The half-life of IdeS was 4.9 (±2.8) hours at 0.24 mg/kg with the main fraction eliminated during 24 hours. Already two hours after IdeS-dosing, the phagocytic capacity of IgG/IgG-fragments was reduced to background levels. Importantly, IdeS has the capacity to inactivate Fc-mediated effector function in vivo, was considered safe with no serious adverse events, and without dose limiting toxicity in this study. The complete, rapid, but temporary removal of IgG provides a new potent therapeutic opportunity in IgG-mediated pathogenic conditions. Trial Registration ClinicalTrials.gov NCT01802697 PMID:26177518

  18. An Hourly Dose-Escalation Desensitization Protocol for Aspirin-Exacerbated Respiratory Disease.

    Science.gov (United States)

    Chen, Justin R; Buchmiller, Brett L; Khan, David A

    2015-01-01

    Aspirin desensitization followed by maintenance therapy effectively improves symptom control in patients with aspirin exacerbated respiratory disease (AERD). The majority of current desensitization protocols use 3-hour dosing intervals and often require 2 to 3 days to complete. We evaluated hourly dose escalations in a subset of patients with chronic rhinosinusitis, nasal polyps, and asthma who historically reacted to aspirin within 1 hour or were avoiding aspirin with the goal of developing a safe and efficient desensitization protocol. Fifty-seven aspirin desensitizations were performed under the hourly protocol. All patients had refractory nasal polyposis as an indication for aspirin desensitization. The clinical characteristics of each subject were analyzed in relation to aspects of his or her reactions during the procedure. Ninety-eight percent of study patients were successfully treated under the hourly protocol, including those with a history of severe reactions and intubation. None required further medication than is available in an outpatient allergy clinic. A total of 96% of reactors recorded a bronchial or naso-ocular reaction within 1 hour of the preceding dose. Of the total patients on this protocol, 40% were able to complete the procedure in a single day, and 60% within 2 days. Patients with AERD who have a history of symptoms less than 1 hour after aspirin exposure can be safely desensitized with a 1-hour dose-escalation protocol that can often be completed in a single day. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  19. Escalation of Intake Under Intermittent Ethanol Access in Diverse Mouse Genotypes

    Science.gov (United States)

    Rosenwasser, Alan M.; Fixaris, Michael C.; Crabbe, John C.; Brooks, Peter C.; Ascheid, Sonja

    2012-01-01

    Experimental animals offered continuous 24-hour free choice access to ethanol rarely display voluntary ethanol consumption at levels sufficient to induce intoxication or to engender dependence. One of the simplest ways to increase voluntary ethanol intake is to impose temporal limitations on ethanol availability. Escalation of ethanol intake has been observed in both rats and mice under a variety of different schedules of alternating ethanol access and deprivation. While such effects have been observed in a variety of rat and mouse genotypes, little is known concerning possible genetic correlations between responses to intermittent ethanol access and other ethanol-related phenotypes. In the present study, we examined the effects of intermittent ethanol access in mouse genotypes characterized by divergent responses to ethanol in other domains, including ethanol preference (C57BL/6J and C3H/HeJ mice), binge-like ethanol drinking (HDID-1 and HS/Npt mice), and ethanol withdrawal severity (WSP-2 and WSR-2 mice). While intermittent ethanol access resulted in escalated ethanol intake in all tested genotypes, the robustness of the effect varied across genotypes. On the other hand, we saw no evidence that the effects of intermittent access are correlated with either binge-like drinking or withdrawal severity, and only weak evidence for a genetic correlation with baseline ethanol preference. Thus, these different ethanol-related traits appear to depend on largely unique sets of genetic mediators. PMID:22862671

  20. De-escalating Antibiotic Use in the Inpatient Setting: Strategies, Controversies, and Challenges.

    Science.gov (United States)

    Daniel Markley, J; Bernard, Shaina; Bearman, Gonzalo; Stevens, Michael P

    2017-04-01

    Antibiotic de-escalation (ADE) is widely accepted as an integral strategy to curtail the global antibiotic resistance crisis. However, there is significant uncertainty regarding the ideal ADE strategy and its true impact on antibiotic resistance. Rapid diagnostic testing has the potential to enhance ADE strategies. Herein, we aim to discuss the current strategies, controversies, and challenges of ADE in the inpatient setting. A consensus definition of ADE remains elusive at this time. Preliminary studies utilizing rapid diagnostic tests including matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), procalcitonin, and other molecular techniques have demonstrated the potential to support ADE strategies. In the absence of evidence-based, highly specific ADE protocols, the likelihood that individual providers will make consistent, often challenging, decisions to de-escalate antibiotic therapy is low. Antimicrobial stewardship programs should support local physicians with ADE and develop innovative ways to integrate ADE into the broader construct of antimicrobial stewardship programs. The evolving field of rapid diagnostics has significant potential to improve ADE strategies, but more research is needed to fully realize this goal.

  1. Stairs or escalator? Using theories of persuasion and motivation to facilitate healthy decision making.

    Science.gov (United States)

    Suri, Gaurav; Sheppes, Gal; Leslie, Sara; Gross, James J

    2014-12-01

    To encourage an increase in daily activity, researchers have tried a variety of health-related communications, but with mixed results. In the present research-using the stair escalator choice context-we examined predictions derived from the Heuristic Systematic Model (HSM), Self Determination Theory (SDT), and related theories. Specifically, we tested whether (as predicted by HSM) signs that encourage heuristic processing ("Take the Stairs") would have greatest impact when placed at the stair/escalator point of choice (when processing time is limited), whereas signs that encourage systematic processing ("Will You Take the Stairs?") would have greatest impact when placed at some distance from the point of choice (when processing time is less limited). We also tested whether (as predicted by SDT) messages promoting autonomy would be more likely to result in sustained motivated behavior (i.e., stair taking at subsequent uncued choice points) than messages that use commands. A series of studies involving more than 9,000 pedestrians provided support for these predictions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  2. How to communicate safety? Some reflections from European project studies

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, Philip; Galson, Daniel (Galson Sciences, 5 Grosvenor House, Melton Road, Oakham, Rutland (United Kingdom))

    2009-12-15

    Attempts to site geological disposal facilities for radioactive waste - and associated public reactions - indicate that communicating safety and demonstrating safety are very different things. The three different approaches to stakeholder engagement undertaken in the context of the PAMINA, ARGONA and CIP projects have provided valuable insights into how risk communication processes and tools can be improved. The approaches used in these projects all involve the participation of interested stakeholders in identifying concerns and issues, which are then examined in a co-operative fashion between stakeholders and developers acting in partnership. Such approaches offer avenues for dialogue and confidence building where such channels were previously not well developed, Full results from the projects will be available in late 2009 for PAMINA and ARGONA and in early 2010 for CIP. The comments and interim insights outlined here will be developed further and incorporated in the overall project outputs, and help inform developing European policy in this area. It is already clear, however, that the approaches used in these projects offer great promise in helping to develop the trust in the institutions and organisations involved that is essential in gaining support and acceptance for the waste management activities now underway across Europe

  3. [Study on the safety of blue light leak of LED].

    Science.gov (United States)

    Shen, Chong-Yu; Xu, Zheng; Zhao, Su-Ling; Huang, Qing-Yu

    2014-02-01

    In this paper, the blue light properties of LED illumination devices have been investigated. Against the status quo of China's LED lighting, we measured the spectrum component of LED lamps and analyzed the photobiological safety under the current domestic and international standards GB/T 20145-2006/CIE S009/E: 2002 and IEC62471: 2006 standards as well as CTL-0744_2009-laser resolution, which provides the reference to the manufacture of LED lighting lamps as well as related safety standards and laws. If the radiance intensity of blue light in LED is lower than 100 W x m(-2) x Sr(-1), there is no harm to human eyes. LEDs will not cause harm to human eyes under normal use, but we should pay attention to the protection of special populations (children), and make sure that they avoid looking at a light source for a long time. The research has found that the blue-rich lamps can affect the human rule of work and rest, and therefore, the LED lamps with color temperature below 4 000 K and color rendering index of 80 are suitable for indoor use. At the same time, the lamps with different parameters should be selected according to the different distances.

  4. Development of a New Safety Culture Assessment Method for Nuclear Power Plants (NPPs) (A study to suggest a new safety culture assessment method in nuclear power plants)

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sang Min; Seong, Poong Hyun [KAIST, Daejeon (Korea, Republic of)

    2014-08-15

    This study is conducted to suggest a new safety culture assessment method in nuclear power plants. Criteria with various existing safety culture analysis methods are united, and reliability analysis methods are applied. The concept of the most representative methods, Fault Tree Analysis (FTA) and Failure Mode and Effect Analysis (FMEA), are adopted to assess safety culture. Through this application, it is expected that the suggested method will bring results with convenience and objectiveness.

  5. Measurement tools and process indicators of patient safety culture in primary care. A mixed methods study by the LINNEAUS collaboration on patient safety in primary care

    Science.gov (United States)

    Parker, Dianne; Wensing, Michel; Esmail, Aneez; Valderas, Jose M

    2015-01-01

    ABSTRACT Background: There is little guidance available to healthcare practitioners about what tools they might use to assess the patient safety culture. Objective: To identify useful tools for assessing patient safety culture in primary care organizations in Europe; to identify those aspects of performance that should be assessed when investigating the relationship between safety culture and performance in primary care. Methods: Two consensus-based studies were carried out, in which subject matter experts and primary healthcare professionals from several EU states rated (a) the applicability to their healthcare system of several existing safety culture assessment tools and (b) the appropriateness and usefulness of a range of potential indicators of a positive patient safety culture to primary care settings. The safety culture tools were field-tested in four countries to ascertain any challenges and issues arising when used in primary care. Results: The two existing tools that received the most favourable ratings were the Manchester patient safety framework (MaPsAF primary care version) and the Agency for healthcare research and quality survey (medical office version). Several potential safety culture process indicators were identified. The one that emerged as offering the best combination of appropriateness and usefulness related to the collection of data on adverse patient events. Conclusion: Two tools, one quantitative and one qualitative, were identified as applicable and useful in assessing patient safety culture in primary care settings in Europe. Safety culture indicators in primary care should focus on the processes rather than the outcomes of care. PMID:26339832

  6. Measurement tools and process indicators of patient safety culture in primary care. A mixed methods study by the LINNEAUS collaboration on patient safety in primary care.

    Science.gov (United States)

    Parker, Dianne; Wensing, Michel; Esmail, Aneez; Valderas, Jose M

    2015-09-01

    There is little guidance available to healthcare practitioners about what tools they might use to assess the patient safety culture. To identify useful tools for assessing patient safety culture in primary care organizations in Europe; to identify those aspects of performance that should be assessed when investigating the relationship between safety culture and performance in primary care. Two consensus-based studies were carried out, in which subject matter experts and primary healthcare professionals from several EU states rated (a) the applicability to their healthcare system of several existing safety culture assessment tools and (b) the appropriateness and usefulness of a range of potential indicators of a positive patient safety culture to primary care settings. The safety culture tools were field-tested in four countries to ascertain any challenges and issues arising when used in primary care. The two existing tools that received the most favourable ratings were the Manchester patient safety framework (MaPsAF primary care version) and the Agency for healthcare research and quality survey (medical office version). Several potential safety culture process indicators were identified. The one that emerged as offering the best combination of appropriateness and usefulness related to the collection of data on adverse patient events. Two tools, one quantitative and one qualitative, were identified as applicable and useful in assessing patient safety culture in primary care settings in Europe. Safety culture indicators in primary care should focus on the processes rather than the outcomes of care.

  7. Perceptions of neighborhood safety and physical activity among youth: the CLAN study.

    Science.gov (United States)

    Carver, Alison; Timperio, Anna; Crawford, David

    2008-05-01

    The purpose of this study was to examine associations between perceptions of neighborhood safety and physical activity among youth. We completed a cross-sectional study of children age 8 to 9 years (n = 188) and adolescents age 13 to 15 years (n = 346) in areas of varying socioeconomic status in Melbourne, Australia. Parents and adolescents completed questionnaires on perceptions of neighborhood safety. Scores were computed for perceptions of road safety, incivilities, and personal safety of the child or adolescent. Moderate-to-vigorous physical activity (MVPA) before or after school, on evenings, and on weekends was recorded using accelerometers. There were no associations between parental perceptions of neighborhood safety and children's MVPA outside school hours. Parental perception of personal safety was positively associated with adolescent boys' MVPA after school. Adolescent girls' concern about road safety was negatively associated with their MVPA during evenings and outside school hours. Perceptions of neighborhood safety might influence physical activity among youth in different ways according to age group and sex.

  8. Impact of random safety analyses on structure, process and outcome indicators: multicentre study.

    Science.gov (United States)

    Bodí, María; Oliva, Iban; Martín, Maria Cruz; Gilavert, Maria Carmen; Muñoz, Carlos; Olona, Montserrat; Sirgo, Gonzalo

    2017-12-01

    To assess the impact of a real-time random safety tool on structure, process and outcome indicators. Prospective study conducted over a period of 12 months in two adult patient intensive care units. Safety rounds were conducted three days a week ascertaining 37 safety measures (grouped into 10 blocks). In each round, 50% of the patients and 50% of the measures were randomized. The impact of this safety tool was analysed on indicators of structure (safety culture, healthcare protocols), process (improvement proportion related to tool application, IPR) and outcome (mortality, average stay, rate of catheter-related bacteraemias and rate of ventilator-associated pneumonia, VAP). A total of 1214 patient-days were analysed. Structure indicators: the use of the safety tool was associated with an increase in the safety climate and the creation/modification of healthcare protocols (sedation/analgesia and weaning). Process indicators: Twelve of the 37 measures had an IPR > 10%; six showed a progressive decrease in the IPR over the study period. Nursing workloads and patient severity on the day of analysis were independently associated with a higher IPR in half of the blocks of variables. Outcome indicators: A significant decrease in the rate of VAP was observed. The real-time random safety tool improved the care process and adherence to clinical practice guidelines and was associated with an improvement in structure, process and outcome indicators.

  9. Monitoring road safety development at regional level: A case study in the ASEAN region.

    Science.gov (United States)

    Chen, Faan; Wang, Jianjun; Wu, Jiaorong; Chen, Xiaohong; Zegras, P Christopher

    2017-09-01

    Persistent monitoring of progress, evaluating the results of interventions and recalibrating to achieve continuous improvement over time is widely recognized as being crucial towards the successful development of road safety. In the ASEAN (Association of Southeast Asian Nations) region there is a lack of well-resourced teams that contain multidisciplinary safety professionals, and specialists in individual countries, who are able to carry out this work effectively. In this context, not only must the monitoring framework be effective, it must also be easy to use and adapt. This paper provides a case study that can be easily reproduced; based on an updated and refined Road Safety Development Index (RSDI), by means of the RSR (Rank-sum ratio)-based model, for monitoring/reporting road safety development at regional level. The case study was focused on the road safety achievements in eleven Southeast Asian countries; identifying the areas of poor performance, potential problems and delays. These countries are finally grouped into several classes based on an overview of their progress and achievements regarding to road safety. The results allow the policymakers to better understand their own road safety progress toward their desired impact; more importantly, these results enable necessary interventions to be made in a quick and timely manner. Keeping action plans on schedule if things are not progressing as desired. This would avoid 'reinventing the wheel' and trial and error approaches to road safety, making the implementation of action plans more effective. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The interplay between teamwork, clinicians' emotional exhaustion, and clinician-rated patient safety: a longitudinal study.

    Science.gov (United States)

    Welp, Annalena; Meier, Laurenz L; Manser, Tanja

    2016-04-19

    Effectively managing patient safety and clinicians' emotional exhaustion are important goals of healthcare organizations. Previous cross-sectional studies showed that teamwork is associated with both. However, causal relationships between all three constructs have not yet been investigated. Moreover, the role of different dimensions of teamwork in relation to emotional exhaustion and patient safety is unclear. The current study focused on the long-term development of teamwork, emotional exhaustion, and patient safety in interprofessional intensive care teams by exploring causal relationships between these constructs. A secondary objective was to disentangle the effects of interpersonal and cognitive-behavioral teamwork. We employed a longitudinal study design. Participants were 2100 nurses and physicians working in 55 intensive care units. They answered an online questionnaire on interpersonal and cognitive-behavioral aspects of teamwork, emotional exhaustion, and patient safety at three time points with a 3-month lag. Data were analyzed with cross-lagged structural equation modeling. We controlled for professional role. Analyses showed that emotional exhaustion had a lagged effect on interpersonal teamwork. Furthermore, interpersonal and cognitive-behavioral teamwork mutually influenced each other. Finally, cognitive-behavioral teamwork predicted clinician-rated patient safety. The current study shows that the interrelations between teamwork, clinician burnout, and clinician-rated patient safety unfold over time. Interpersonal and cognitive-behavioral teamwork play specific roles in a process leading from clinician emotional exhaustion to decreased clinician-rated patient safety. Emotionally exhausted clinicians are less able to engage in positive interpersonal teamwork, which might set in motion a vicious cycle: negative interpersonal team interactions negatively affect cognitive-behavioral teamwork and vice versa. Ultimately, ineffective cognitive

  11. Patient safety subcultures among registered nurses and nurse assistants in Swedish hospital care: a qualitative study.

    Science.gov (United States)

    Danielsson, Marita; Nilsen, Per; Ohrn, Annica; Rutberg, Hans; Fock, Jenni; Carlfjord, Siw

    2014-01-01

    Patient safety culture emerges from the shared assumptions, values and norms of members of a health care organization, unit, team or other group with regard to practices that directly or indirectly influence patient safety. It has been argued that organizational culture is an amalgamation of many cultures, and that subcultures should be studied to develop a deeper understanding of an organization's culture. The aim of this study was to explore subcultures among registered nurses and nurse assistants in Sweden in terms of their assumptions, values and norms with regard to practices associated with patient safety. The study employed an exploratory design using a qualitative method, and was conducted at two hospitals in southeast Sweden. Seven focus group interviews and two individual interviews were conducted with registered nurses and seven focus group interviews and one individual interview were conducted with nurse assistants. Manifest content analysis was used for the analysis. Seven patient safety culture domains (i.e. categories of assumptions, values and norms) that included practices associated with patient safety were found: responsibility, competence, cooperation, communication, work environment, management and routines. The domains corresponded with three system levels: individual, interpersonal and organizational levels. The seven domains consisted of 16 subcategories that expressed different aspects of the registered nurses and assistants nurses' patient safety culture. Half of these subcategories were shared. Registered nurses and nurse assistants in Sweden differ considerably with regard to patient safety subcultures. The results imply that, in order to improve patient safety culture, efforts must be tailored to both registered nurses' and nurse assistants' patient safety-related assumptions, values and norms. Such efforts must also take into account different system levels. The results of the present study could be useful to facilitate discussions

  12. Safety of the open-irrigated ablation catheter for radiofrequency ablation: safety analysis from six clinical studies.

    Science.gov (United States)

    Waldo, Albert L; Wilber, David J; Marchlinski, Francis E; Stevenson, William G; Aker, Brenda; Boo, Lee Ming; Jackman, Warren M

    2012-09-01

    The open-irrigated catheter is used most frequently for atrial and ventricular radiofrequency ablation (RFA), and is often considered as the standard by which new ablation systems are compared. But few data have been published concerning its safety. This report provides a comprehensive safety analysis of the use of an open-irrigated catheter for RFA of atrial flutter, ventricular tachycardia, and atrial fibrillation in 1,275 patients in six rigorously monitored, prospective, multicenter studies. This analysis is of data from six studies conducted as part of both Food and Drug Administration-mandated investigational device exemption studies and postapproval studies. The six studies span a period of more than 10 years. All serious RFA complications and vascular access complications that occurred within seven days postprocedure were included. The number of patients who experienced any acute serious RFA complication in these studies combined was 4.9% (63/1,275). The two earliest studies were conducted when the open-irrigated catheter was first introduced, and accounted for 55.6% of the complications. In the first atrial flutter ablation study, RFA complications decreased by 60% (15.4%-6.2%) after a proctoring program was initiated during the study. For all studies, vascular access complications ranged between from 0.5%-4.7%, and no stroke or transient ischemic attack was reported within 7 days postprocedure. No significant pulmonary vein stenosis was reported from the atrial fibrillation studies. A proctoring program, careful fluid management, and absence of char and coagulum contributed to the safe use of the open-irrigated RFA catheter. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

  13. A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin.

    Science.gov (United States)

    Gray, Jhanelle E; Infante, Jeffrey R; Brail, Les H; Simon, George R; Cooksey, Jennifer F; Jones, Suzanne F; Farrington, Daphne L; Yeo, Adeline; Jackson, Kimberley A; Chow, Kay H; Zamek-Gliszczynski, Maciej J; Burris, Howard A

    2015-12-01

    LY2090314 (LY) is a glycogen synthase kinase 3 inhibitor with preclinical efficacy in xenograft models when combined with platinum regimens. A first-in-human phase 1 dose-escalation study evaluated the combination of LY with pemetrexed/carboplatin. Forty-one patients with advanced solid tumors received single-dose LY monotherapy lead-in and 37 patients received LY (10-120 mg) plus pemetrexed/carboplatin (500 mg/m(2) and 5-6 AUC, respectively) across 8 dose levels every 21 days. Primary objective was maximum tolerated dose (MTD) determination; secondary endpoints included safety, antitumor activity, pharmacokinetics, and beta-catenin pharmacodynamics. MTD of LY with pemetrexed/carboplatin was 40 mg. Eleven dose-limiting toxicities (DLTs) occurred in ten patients. DLTs during LY monotherapy occurred at ≥ 40 mg: grade 2 visual disturbance (n = 1) and grade 3/4 peri-infusional thoracic pain during or shortly post infusion (n = 4; chest, upper abdominal, and back pain). Ranitidine was added after de-escalation to 80 mg LY to minimize peri-infusional thoracic pain. Following LY with pemetrexed/carboplatin therapy, DLTs included grade 3/4 thrombocytopenia (n = 4) and grade 4 neutropenia (n = 1). Best overall response by RECIST included 5 confirmed partial responses (non-small cell lung cancer [n = 3], mesothelioma, and breast cancer) and 19 patients having stable disease. Systemic LY exposure was approximately linear over dose range studied. Transient upregulation of beta-catenin measured in peripheral blood mononuclear cells (PBMCs) occurred at 40 mg LY. The initial safety profile of LY2090314 was established. MTD LY dose with pemetrexed/carboplatin is 40 mg IV every 3 weeks plus ranitidine. Efficacy of LY plus pemetrexed/carboplatin requires confirmation in randomized trials.

  14. Surrounded by Safety : Safety As An Encompassing Policy Concept in The Netherlands. European Journal of Policing Studies.

    NARCIS (Netherlands)

    Resodihardjo, S.; Prins, R.S.

    2014-01-01

    Safety used to be a pretty straightforward concept: governments need to safeguard the country from invasion and its citizens from crime. Over time, additional issues became to be defined as a safety problem. Even so, the safety problems and their accompanying policies remained clearly demarcated –

  15. Parametric study for the fire safety design of steel structures

    DEFF Research Database (Denmark)

    Aiuti, Riccardo; Giuliani, Luisa

    2013-01-01

    or hindered thermal expansion induced on the element by the rest of the structure. Nevertheless, restrained thermal expansion is known to significantly affect the behaviour of steel structures in fire, and the compliance with a prescribed resistance class doesn’t ensure the integrity of the building after...... the considered time of fire exposure. A deeper knowledge on the failure mode of steel structure is however important in order to ensure the safety of the people and properties outside the building. Aim of this paper is to analyze the behaviour of single elements, sub-assemblies and frames exposed to fire...... and find out the basic collapse mechanisms of structural elements in fire conditions, considering the rest of the construction with appropriate constraints. The analysis is carried out taking into account material and geometrical nonlinearities as well as the degradation of steel properties at high...

  16. Vessel traffic safety in busy waterways: A case study of accidents in western shenzhen port.

    Science.gov (United States)

    Mou, J M; Chen, P F; He, Y X; Yip, Tsz Leung; Li, W H; Tang, J; Zhang, H Z

    2016-08-03

    Throughout the world, busy waterways near large ports witness heavy vessel traffic in recent decades. The waterways are characterized by high risk in terms of loss of life, property, and pollution to environment. To facilitate maritime safety management with satisfactory efficiency and efficacy, the authors propose a framework of safety indexes to evaluate the risk level in busy waterways according to the accident severity, fatality rate and special indicators of maritime transportation. The safety indexes consist of Safety Evaluation Index (SEI) and Safety Warning Index (SWI), and are derived from the proposed risk criteria of Chinese vessel traffic. As a case study, data on vessel traffic accidents reported in the Western Shenzhen Port, South China from 1995 to 2015 are analyzed. The actual risk level of this area during the period is calculated under the framework. The implementation of the safety indexes indicate that the risk criteria and safety indexes are practicable and effective for the vessel traffic management. The methodology based on long-term accident data can significantly support the risk analysis in the macroscopic perspective for busy ports and waterways, such that SWI can act as threshold to trigger actions, while SEI can act as an indicator to measure safety status. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-PET incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

  18. Food safety challenges--a Pakistan's perspective.

    Science.gov (United States)

    Akhtar, Saeed

    2015-01-01

    Biological, chemical, and physical contamination of foods is a terrifying threat for the health and economic growth in developing societies. Rampantly available literature on foodborne illnesses especially diarrhea among children exclusively depicts the intensified disease burden associated with foodborne illness in the underdeveloped economies. Prevalence of many pathogens in several foods is commonplace in Pakistan. Precise estimates for foodborne illnesses in Pakistan are hard to make because of the absence of any monitoring, surveillance, and infection control. Poor processing and storage of milk, cereal grains, and nuts are a major cause of aflatoxin contamination and mold proliferation. Numerous studies manifest a multitude of foods to be contaminated with heavy metals. Escalating population growth limits the economic potential of the individual and the state through a tendency among the traders and manufacturers to intentionally debase food commodities offered for sale to make profit at the cost of their quality and safety. Therefore, a growing trend of adulteration in foods during the recent past, particularly adulteration of milk, poses a pressing challenge for the government. This review is a concerted attempt to elucidate the prevailing food safety scenario in Pakistan. Information derived from local and related international studies will be presented to clearly depict a picture of food safety in Pakistan. It is proposed that an extensive food safety infrastructure leading to a safer supply of foods needs to be devised, designed, and implemented.

  19. Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Geier, M.; Astner, S.T.; Duma, M.N.; Putzhammer, J.; Winkler, C.; Molls, M.; Geinitz, H. [Technische Univ. Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Jacob, V. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde; Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Care; Tromsoe Univ. (Norway). Inst. of Clinical Medicine

    2012-05-15

    The goal of this work was to assess the feasibility of moderately hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer regarding acute side effects and dose-volume histogram data (DVH data). Acute side effects and DVH data were evaluated of the first 40 intermediate risk prostate cancer patients treated with a definitive daily image-guided SIB-IMRT protocol via helical tomotherapy in our department. The planning target volume including the prostate and the base of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. The boost volume containing the prostate and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of 76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall were set in order not to exceed the dose of 76 Gy prescribed to the boost volume. Acute toxicity was evaluated prospectively using a modified CTCAE (Common Terminology Criteria for Adverse Events) score. SIB-IMRT allowed good rectal sparing, although the full boost dose was permitted to the anterior rectal wall. Median rectum dose was 38 Gy in all patients and the median volumes receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and 3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and urological side effects occurred in 25% and 57.5%, respectively. No correlation was found between acute toxicity and the DVH data. This institutional SIB-IMRT protocol using daily image guidance as a precondition for smaller safety margins allows dose escalation to the prostate without increasing acute toxicity. (orig.)

  20. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of); Lee, Jae Young; Park, Kun Chul [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2003-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SDS-1, SDS2, ECCS, and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  1. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong; Lee, Jae Young; Bang, Kwang Hyun [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2001-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SOS-1, SOS-2, ECCS and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  2. Do Sell-Side Stock Analysts Exhibit Escalation of Commitment?

    Science.gov (United States)

    Beshears, John; Milkman, Katherine L

    2011-03-01

    This paper presents evidence that when an analyst makes an out-of-consensus forecast of a company's quarterly earnings that turns out to be incorrect, she escalates her commitment to maintaining an out-of-consensus view on the company. Relative to an analyst who was close to the consensus, the out-of-consensus analyst adjusts her forecasts for the current fiscal year's earnings less in the direction of the quarterly earnings surprise. On average, this type of updating behavior reduces forecasting accuracy, so it does not seem to reflect superior private information. Further empirical results suggest that analysts do not have financial incentives to stand by extreme stock calls in the face of contradictory evidence. Managerial and financial market implications are discussed.

  3. Maternal risk taking on the balloon analogue risk task as a prospective predictor of youth alcohol use escalation.

    Science.gov (United States)

    Banducci, Anne N; Felton, Julia W; Dahne, Jennifer; Ninnemann, Andrew; Lejuez, C W

    2015-10-01

    The transition from late childhood through middle adolescence represents a critical developmental period during which there is a rapid increase in the initiation and escalation of alcohol use. Alcohol use is part of a constellation of risk taking behaviors that increase during this developmental transition, which can be explained by environmental and genetic factors. Social learning theory (SLT) implicates observations of parental drinking in the development of alcohol use in youth. Parental risk taking more broadly has not previously been examined as a factor predictive of alcohol use escalation in youth across adolescence. The current study examined the relative contributions of maternal risk taking on the Balloon Analogue Risk Task (BART) and maternal alcohol use in the prediction of alcohol escalation among youth over three years. Participants were a sample of 245 youth (55.0% male, 49.6% Caucasian) who participated annually between grades 8 and 10, drawn from a larger study of adolescent risk taking. Within our sample, maternal risk taking, as measured by the BART, predicted increases in alcohol use. Interestingly, maternal alcohol use and other youth factors were not predictive of escalations in youth alcohol use. Our findings suggest the importance of considering maternal riskiness more broadly, rather than solely focusing on maternal alcohol use when attempting to understand youth alcohol use across adolescence. These findings emphasize the relevance of maternal risk taking as measured by a behavioral task and suggest a general level of riskiness displayed by mothers might encourage youth to behave in a riskier manner themselves. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Safety Culture and Mortality after Acute Myocardial Infarction: A Study of Medicare Beneficiaries at 171 Hospitals.

    Science.gov (United States)

    Shahian, David M; Liu, Xiu; Rossi, Laura P; Mort, Elizabeth A; Normand, Sharon-Lise T

    2017-10-09

    To investigate the association between hospital safety culture and 30-day risk-adjusted mortality for Medicare patients with acute myocardial infarction (AMI) in a large, diverse hospital cohort. The final analytic cohort consisted of 19,357 Medicare AMI discharges (MedPAR data) linked to 257 AHRQ Hospital Survey on Patient Safety Culture surveys from 171 hospitals between 2008 and 2013. Observational, cross-sectional study using hierarchical logistic models to estimate the association between hospital safety scores and 30-day risk-adjusted patient mortality. Odds ratios of 30-day, all-cause mortality, adjusting for patient covariates, hospital characteristics (size and teaching status), and several different types of safety culture scores (composite, average, and overall) were determined. No significant association was found between any measure of hospital safety culture and adjusted AMI mortality. In a large cross-sectional study from a diverse hospital cohort, AHRQ safety culture scores were not associated with AMI mortality. Our study adds to a growing body of investigations that have failed to conclusively demonstrate a safety culture-outcome association in health care, at least with widely used national survey instruments. © Health Research and Educational Trust.

  5. A hybrid simulation approach for integrating safety behavior into construction planning: An earthmoving case study.

    Science.gov (United States)

    Goh, Yang Miang; Askar Ali, Mohamed Jawad

    2016-08-01

    One of the key challenges in improving construction safety and health is the management of safety behavior. From a system point of view, workers work unsafely due to system level issues such as poor safety culture, excessive production pressure, inadequate allocation of resources and time and lack of training. These systemic issues should be eradicated or minimized during planning. However, there is a lack of detailed planning tools to help managers assess the impact of their upstream decisions on worker safety behavior. Even though simulation had been used in construction planning, the review conducted in this study showed that construction safety management research had not been exploiting the potential of simulation techniques. Thus, a hybrid simulation framework is proposed to facilitate integration of safety management considerations into construction activity simulation. The hybrid framework consists of discrete event simulation (DES) as the core, but heterogeneous, interactive and intelligent (able to make decisions) agents replace traditional entities and resources. In addition, some of the cognitive processes and physiological aspects of agents are captured using system dynamics (SD) approach. The combination of DES, agent-based simulation (ABS) and SD allows a more "natural" representation of the complex dynamics in construction activities. The proposed hybrid framework was demonstrated using a hypothetical case study. In addition, due to the lack of application of factorial experiment approach in safety management simulation, the case study demonstrated sensitivity analysis and factorial experiment to guide future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Are nurse presenteeism and patient safety culture associated: a cross-sectional study.

    Science.gov (United States)

    Brborović, Hana; Brborović, Ognjen; Brumen, Vlatka; Pavleković, Gordana; Mustajbegović, Jadranka

    2014-06-01

    Working as a nurse involves great dedication and sacrifice: working night shifts, working overtime, and coming to work sick. The last is also known as presenteeism. Research has shown that poor nurse performance can affect both caregiver's and patient's safety. The aim of this cross-sectional study was to investigate whether nurse presenteeism affected patient safety culture and to look deeper into the characteristics of nurse presenteeism and patient safety culture in Croatia. The study was conducted in one general hospital in Croatia over April and May 2012 and specifically targeted medical nurses as one of the largest groups of healthcare professionals. They were asked to fill two questionnaires: the six-item Stanford Presenteeism Scale (SPS-6) and the Hospital Survey on Patient Safety Culture (HSOPSC). We found no association between presenteeism and patient safety culture. Overall positive perception of safety was our sample's strength, but other dimensions were positively rated by less than 65 % of participants. The lowest positive response concerned "nonpunitive response to error", which is consistent with previous studies. Presenteeist nurses did not differ in their characteristics from nurses without presenteeism (gender, age, years of experience, working hours, contact with patients and patient safety grades). Our future research will have to include a broader healthcare population for us to be able to identify weak spots and suggest improvements toward high-quality and cost-effective health care.

  7. Safety Improvements on Wood Chippers Currently in Use: A Study on Feasibility in the Italian Context

    Directory of Open Access Journals (Sweden)

    Giorgia Bagagiolo

    2017-12-01

    Full Text Available Following formal opposition by France, the harmonized safety standards regarding manually-loaded wood chippers (EN 13525:2005+A2:2009 which presumed compliance with the Essential Health and Safety Requirements (EHSR required by the Machine Directive (Directive 2006/42/EC, have recently been withdrawn, and a new draft of the standard is currently under revision. In order to assess the potential impact of the expected future harmonized standards within the Italian context, this study has examined the main issues in implementing EHSRs on wood chippers already being used. Safety issues regarding wood chippers already in use were identified in an analysis of the draft standard, through the observation of a number of case studies, and qualitative analysis of the essential technical interventions. A number of agricultural and forestry operators and companies participated in the study, pointing out the technical and economic obstacle facing the safety features requested by the pending new standard. It emerged that the main safety issues concerned the implementation of the reverse function, the stop bar, and the protective devices, the infeed chute dimension, the emergency stop function, and the designated feeding area. The possibility of adopting such solutions mainly depends on technical feasibility and costs, but an important role is also played by the attitude towards safety and a lack of adequate information regarding safety obligations and procedures among users.

  8. Patient's safety culture among Tunisian healthcare workers: results of a cross sectional study in university hospital.

    Science.gov (United States)

    Cheikh, Asma Ben; Bouafia, Nabiha; Mahjoub, Mohamed; Ezzi, Olfa; Nouira, Amel; Njah, Mansour

    2016-01-01

    Healthcare safety has become a public health priority in developed world. Development of safety culture care is fundamental pillar to any strategy for improving quality and safety care. The objective of this study is to measure level of patients' safety culture among healthcare professionals at university hospital, center Farhat Hached Sousse (Tunisia). We conducted, in 2013, a descriptive study among all licensed physicians (n= 116) and a representative sample of paramedical staff (n= 203) exercising at university hospital center Farhat Hached Sousse (Tunisia). Measuring instrument used is a valid questionnaire containing ten safety care dimensions. Data were analyzed using SPSS version 19. The response rates were 74.1% for physicians and 100% for paramedical staff. Overall score of different dimensions varies between 32.7% and 68.8%. Dimension having most developed score (68.8%) was perception of "Frequency and reporting adverse events". Dimension with lowest score (32.7%) was "Management support for safety care". Our study has allowed us to conclude that all dimensions of patients' safety culture need to be improved among our establishment's professionals. Therefore, more efforts are necessary in order to develop a security culture based on confidence, learning, communication and team work and rejecting sanction, blame, criminalization and punitive reporting.

  9. Improving safety in high-speed work zones : a Super 70 study.

    Science.gov (United States)

    2011-01-01

    Super 70 was an urban reconstruction project (March-November 2007) along I-70 in the central part of Indianapolis. INDOT : applied in that project several innovative and traditional solutions. This study investigates the safety effect of the solution...

  10. The interplay between teamwork, clinicians' emotional exhaustion, and clinician-rated patient safety: a longitudinal study

    National Research Council Canada - National Science Library

    Welp, Annalena; Meier, Laurenz L; Manser, Tanja

    2016-01-01

    .... The current study focused on the long-term development of teamwork, emotional exhaustion, and patient safety in interprofessional intensive care teams by exploring causal relationships between these constructs...

  11. Are nurse presenteeism and patient safety culture associated: a cross-sectional study

    National Research Council Canada - National Science Library

    Hana Brborović; Ognjen Brborović; Vlatka Brumen; Gordana Pavleković; Jadranka Mustajbegović

    2014-01-01

    .... The aim of this cross-sectional study was to investigate whether nurse presenteeism affected patient safety culture and to look deeper into the characteristics of nurse presenteeism and patient...

  12. Review of Studies on Pedestrian and Bicyclist Safety, 1991-2007

    Science.gov (United States)

    2012-06-01

    This report reviews the pedestrian and bicyclist safety research literature in print as of 2007. It summarizes and synthesizes the key studies, evaluates existing knowledge and identifies research gaps and provides recommendations for future directio...

  13. Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study

    DEFF Research Database (Denmark)

    Larsen, T H; Poulsen, Lars K.; Melac, M

    2006-01-01

    A single-centre, randomized, double-blind, placebo-controlled study. Aims: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis....

  14. Evaluation of the safety and efficacy of TY-51924 in patients with ST elevated acute myocardial infarction - Early phase II first in patient pilot study.

    Science.gov (United States)

    Takayama, Tadateru; Kimura, Kazuo; Fukuzawa, Shigeru; Hirayama, Haruo; Sone, Takahito; Ueda, Yasunori; Uematsu, Masaaki; Ishihara, Masaharu; Nakao, Koichi; Matsumoto, Naoya; Kosuge, Masami; Hiro, Takafumi; Asakura, Masanori; Kaneko, Akira; Yokoi, Toshiaki; Hirayama, Atsushi

    2016-02-01

    In myocardial ischemia-reperfusion injuries, the involvement of the Na(+)/H(+) exchanger (NHE) is considered to be one of the pathogenic mechanisms following reperfusion. TY-51924 is a novel hydrophilic NHE inhibitor with a lower risk of central neurotoxicity than previous NHE inhibitors. This open-label, dose-escalating study was undertaken to investigate the safety, efficacy, and pharmacokinetics of TY-51924 in patients with ST-elevation myocardial infarction (STEMI). Consent was obtained from a total of 30 patients with first anterior STEMI. After 12 patients were determined to be ineligible, the remaining 18 patients, each of whom was undergoing primary percutaneous coronary intervention (pPCI), received TY-51924 intravenously up to 10, 20, or 30mg/kg as the low-, medium-, or high-dose groups, respectively (n=6 in each group). The primary endpoints were safety (up to 7 days) and plasma drug concentration. The myocardial salvage index (MSI) was measured by (201)Tl/(123)I-beta-methyl-p-iodophenyl pentadecanoic acid single photon emission computed tomography (SPECT) 3-5 days after pPCI. No side effects were observed. Plasma drug concentrations increased dose-dependently, and were subsequently eliminated rapidly. MSIs were 0.118, 0.335, and 0.192 in the low-, medium-, and high-dose groups, respectively. In additional analysis, the combined MSIs in the medium- and high-dose groups were significantly higher than those in the low-dose group, in patients with a longer time from symptom onset to reperfusion (p=0.0247). No side effects were observed even at the highest dose with this novel hydrophilic NHE inhibitor. Therefore, TY-51924 is thought to be safe in patients with STEMI, even at the highest dose. Potential cardioprotective effects of intravenous TY-51924 might be expected based on the results obtained for the MSIs using SPECT at 20-30mg/kg. However, further large-scale, double-blind, placebo-controlled clinical studies are required to confirm the efficacy and

  15. How organizational escalation prevention potential affects success of implementation of innovations: Electronic medical records in hospitals

    NARCIS (Netherlands)

    M.S. Lambooij (Mattijs); F. Koster (Ferry)

    2016-01-01

    textabstractBackground: Escalation of commitment is the tendency that (innovation) projects continue, even if it is clear that they will not be successful and/or become extremely costly. Escalation prevention potential (EPP), the capability of an organization to stop or steer implementation

  16. Patients' evaluations of patient safety in English general practices: a cross-sectional study.

    Science.gov (United States)

    Ricci-Cabello, Ignacio; Marsden, Kate S; Avery, Anthony J; Bell, Brian G; Kadam, Umesh T; Reeves, David; Slight, Sarah P; Perryman, Katherine; Barnett, Jane; Litchfield, Ian; Thomas, Sally; Campbell, Stephen M; Doos, Lucy; Esmail, Aneez; Valderas, Jose M

    2017-07-01

    Description of safety problems and harm in general practices has previously relied on information from health professionals, with scarce attention paid to experiences of patients. To examine patient-reported experiences and outcomes of patient safety in primary care. Cross-sectional study in 45 general practices across five regions in the north, centre, and south of England. A version of the Patient Reported Experiences and Outcomes of Safety in Primary Care (PREOS-PC) questionnaire was sent to a random sample of 6736 patients. Main outcome measures included 'practice activation' (what a practice does to create a safe environment); 'patient activation' (how proactive are patients in ensuring safe healthcare delivery); 'experiences of safety events' (safety errors); 'outcomes of safety' (harm); and 'overall perception of safety' (how safe patients rate their practice). Questionnaires were returned by 1244 patients (18.4%). Scores were high for 'practice activation' (mean [standard error] = 80.4 out of 100 [2.0]) and low for 'patient activation' (26.3 out of 100 [2.6]). Of the patients, 45% reported experiencing at least one safety problem in the previous 12 months, mostly related to appointments (33%), diagnosis (17%), patient provider communication (15%), and coordination between providers (14%). Twenty-three per cent of the responders reported some degree of harm in the previous 12 months. The overall assessment of level of safety of practices was generally high (86.0 out of 100 [16.8]). Priority areas for patient safety improvement in general practices in England include appointments, diagnosis, communication, coordination, and patient activation. © British Journal of General Practice 2017.

  17. AN EMPIRICAL STUDY OF THE DETERMINANTS OF SAFETY-NET HOSPITAL FAILURES

    OpenAIRE

    Devin Alan Daugherty; Ernesto Escobedo

    2013-01-01

    Several safety-net hospitals have closed in the United States, but the scholarly literature does not adequately explain why. This study examines the relationship between the operational status (open or closed) of safety-net hospitals and unemployment, median household income, gross profit margin, efficiency ratio, operating margin, excess margin, and salary and benefit expenses per full-time equivalent. Study data were collected and analyzed by means of a logistic regression analysis. A signi...

  18. An open-label, 6-month study of allopurinol safety in gout: The LASSO study.

    Science.gov (United States)

    Becker, Michael A; Fitz-Patrick, David; Choi, Hyon K; Dalbeth, Nicola; Storgard, Chris; Cravets, Matt; Baumgartner, Scott

    2015-10-01

    Allopurinol is the most widely prescribed serum uric acid-lowering therapy (ULT) in gout. To achieve serum uric acid (sUA) concentrations associated with clinical benefit, allopurinol is serially uptitrated with sUA monitoring. Suboptimal dosing is a key contributor to poor clinical outcomes, but few data are available on the safety and efficacy of dose-titrated allopurinol, particularly at doses > 300 mg/d. The objective of this open-label study was to investigate the safety and efficacy of allopurinol under conditions where investigators were encouraged to titrate to optimal, medically appropriate doses. Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) was a large, 6-month, multicenter study of allopurinol (NCT01391325). Adults meeting American Rheumatism Association Criteria for Classification of Acute Arthritis of Primary Gout and ≥ 2 gout flares in the previous year were eligible. Investigators were encouraged (but not required) to titrate allopurinol doses to achieve target sUA gout flare frequency. Of 1735 patients enrolled, 1732 received ≥ 1 allopurinol doses. The maximal daily allopurinol dose during study was 300 mg in 20.2% of patients; dosing duration was 115.5, 152.0, and 159.7 days, respectively. Overall, baseline demographic characteristics and comorbidity rates were similar across these three categories, but patients receiving > 300-mg maximal dose had more severe gout. Treatment-emergent adverse events possibly related to allopurinol occurred in 15.2%, 9.5%, and 11.4% of patients in the 300-mg categories, respectively. Rash incidence was low (1.5%) and allopurinol hypersensitivity syndrome was not reported. No clinically meaningful changes occurred in laboratory values. sUA 300 mg, respectively. This large multicenter study found that the allopurinol dose-titration strategy was well tolerated, without new safety signals emerging over 6 months. However, despite encouragement to treat to target, significant

  19. The role of safety signals in fear extinction: An analogue study.

    Science.gov (United States)

    Restrepo-Castro, Juan C; Castro-Camacho, Leonidas; Javier Labrador, Francisco

    2017-12-01

    Safety signals are conditioned inhibitory stimuli that indicate the absence of unconditioned stimuli. It is not clear whether the presence of safety signals is detrimental or beneficial in extinction-based interventions. The purpose of this study was to evaluate the effect of safety signals on autonomic and expectancy fear-related responses. Following the conditional discrimination paradigm (AX +, BX-), undergraduate students (N = 48) underwent an aversive conditioning procedure, while safety signals were experimentally created. Participants were randomly assigned to one of two conditions during extinction: presence or absence of safety signals. Significant reductions of fear-related responses were found in both groups. Expectancy measures showed that the presence of safety signals did not interfere with reduction of fear related responses at follow-up. The analogue nature of the study affects its ecological validity. There are some methodological issues. Safety signals did not interfere with extinction learning. Attention may be a mechanism associated with the maintenance of fear responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Safety-related regulatory actions for orphan drugs in the US and EU: a cohort study.

    Science.gov (United States)

    Heemstra, Harald E; Giezen, Thijs J; Mantel-Teeuwisse, Aukje K; de Vrueh, Remco L A; Leufkens, Hubert G M

    2010-02-01

    Drugs for rare diseases, so-called orphan drugs, are often intended for serious or chronically debilitating diseases. Safety information is more limited at the time of approval for orphan drugs as a result of various factors, such as the limited number of patients in clinical trials, quality of the clinical trials and special approval procedures. Several studies have been conducted on safety-related regulatory actions for drugs, but none of these have specifically focused on orphan drugs. To determine the frequency and nature of safety-related regulatory actions for orphan drugs in the US and EU. This cohort study examined publicly available data from the websites of US and EU regulatory authorities on orphan drugs approved in the US and/or the EU between January 2000 and December 2007. The main outcome measures were the nature, frequency and timing of safety-related regulatory actions, defined as (i) safety withdrawals; (ii) 'black-box' warnings; and (iii) written communications to healthcare professionals issued by the US FDA or the European Medicines Agency between January 2000 and June 2008. Ninety-five orphan drugs were approved during the study period (75 in the US, 44 in the EU, and 24 in both regions). Ten products (10.5%) received a safety-related regulatory action. No safety withdrawals, four black-box warnings and 12 written communications were identified. The probability of a first safety-related regulatory action for orphan drugs was 20.3% after 8 years of follow-up. Orphan drugs approved by accelerated approval (relative risk [RR] 3.32; 95% CI 1.06, 10.42), oncological products (RR 7.83; 95% CI 0.96, 63.82) and products for gastrointestinal and metabolism indications (RR 10.44; 95% CI 1.25, 87.27) may have a higher risk for a safety-related regulatory action. The probability of a first safety-related regulatory action for an orphan drug was slightly lower than that reported in the literature for biologicals in one study and new molecular entities in

  1. System and safety studies of accelerator driven systems for transmutation. Annual report 2007

    Energy Technology Data Exchange (ETDEWEB)

    Arzhanov, Vasily; Fokau, Andrei; Persson, Calle; Runevall, Odd; Sandberg, Nils; Tesinsky, Milan; Wallenius, Janne; Youpeng Zhang (Div. of Reactor Physics, Royal Institute of Technology, Stockholm (Sweden))

    2008-05-15

    Within the project 'System and safety studies of accelerator driven systems for transmutation', research on design and safety of sub-critical reactors for recycling of minor actinides is performed. During 2007, the reactor physics division at KTH has calculated safety parameters for EFIT-400 with cermet fuel, permitting to start the transient safety analysis. The accuracy of different reactivity meters applied to the YALINA facility was assessed and neutron detection studies were performed. A model to address deviations from point kinetic behaviour was developed. Studies of basic radiation damage physics included calculations of vacancy formation and activation enthalpies in bcc niobium. In order to predict the oxygen potential of inert matrix fuels, a thermo-chemical model for mixed actinide oxides was implemented in a phase equilibrium code

  2. A Study on Performance and Safety Tests of Electrosurgical Equipment.

    Science.gov (United States)

    Tavakoli Golpaygani, A; Movahedi, M M; Reza, M

    2016-09-01

    Modern medicine employs a wide variety of instruments with different physiological effects and measurements. Periodic verifications are routinely used in legal metrology for industrial measuring instruments. The correct operation of electrosurgical generators is essential to ensure patient's safety and management of the risks associated with the use of high and low frequency electrical currents on human body. The metrological reliability of 20 electrosurgical equipment in six hospitals (3 private and 3 public) was evaluated in one of the provinces of Iran according to international and national standards. The achieved results show that HF leakage current of ground-referenced generators are more than isolated generators and the power analysis of only eight units delivered acceptable output values and the precision in the output power measurements was low. Results indicate a need for new and severe regulations on periodic performance verifications and medical equipment quality control program especially in high risk instruments. It is also necessary to provide training courses for operating staff in the field of meterology in medicine to be acquianted with critical parameters to get accuracy results with operation room equipment.

  3. A Study on Performance and Safety Tests of Electrosurgical Equipment

    Directory of Open Access Journals (Sweden)

    Tavakoli Golpaygani A.

    2016-09-01

    Full Text Available Introduction: Modern medicine employs a wide variety of instruments with different physiological effects and measurements. Periodic verifications are routinely used in legal metrology for industrial measuring instruments. The correct operation of electrosurgical generators is essential to ensure patient’s safety and management of the risks associated with the use of high and low frequency electrical currents on human body. Material and Methods: The metrological reliability of 20 electrosurgical equipment in six hospitals (3 private and 3 public was evaluated in one of the provinces of Iran according to international and national standards. Results: The achieved results show that HF leakage current of ground-referenced generators are more than isolated generators and the power analysis of only eight units delivered acceptable output values and the precision in the output power measurements was low. Conclusion: Results indicate a need for new and severe regulations on periodic performance verifications and medical equipment quality control program especially in high risk instruments. It is also necessary to provide training courses for operating staff in the field of meterology in medicine to be acquianted with critical parameters to get accuracy results with operation room equipment.

  4. Safety evaluation studies of Citrullus colocynthis for diabetes in rats

    Directory of Open Access Journals (Sweden)

    S.K Atole

    Full Text Available An experiment conducted in the department of Pharmacology and Toxicology, Nagpur Veterinary College, Nagpur reported Citrullus colocynthis to posses antidiabetic effect in rats at the rate of 50 mg/kg b.w and 100mg/kg b.w. So it was decided to also evaluate the safety of Citrullus colocynthis in rats at its antidiabetic dose. The experiment was conducted for 28 days .18 wistar rats were divided into three groups containing six rats in each group. Group T1 was maintained as normal control, whereas groups T2 and T3 received aqueous extract of Citrullus colocynthis @ 50 and 100 mg/kg body weight. Haematological and Biochemical estimations were done at the end of experiment i.e. on 29th day by using standard kits. Rats were then sacrificed and histopathological examinations were done. The results obtained showed that Citrullus colocynthis is safe at its antidiabetic dose and is safe for use as an antidiabetic remedy. [Vet World 2009; 2(11.000: 423-425

  5. Child safety in parks' playgrounds (a case study in Tehran’s sub-district parks

    Directory of Open Access Journals (Sweden)

    A.H. Mirlouhi Falavarjani

    2010-10-01

    Full Text Available Background and aimsSafety is a complex concept and multidisciplinary science which is included some difference areas from industrial sectors to urban public arenas. Parks and playgrounds as important public places should be considered in terms of health and safety, especially for kids as prominent social vulnerable citizens. According to CPSC, 147 deaths havebeen reported for under 15 year old child during Jan 1990 to Aug 2000. Every 2.5 minute, kid suffers playground related accident. The main objective in this study is safety assessment ofplaygrounds among the selected parks.MethodsIn this case study, deductive approach and cross-sectional survey was followed, and some parks and playgrounds were selected among five urban counties in Tehran. Our volunteered samples were 160 parents. Playgrounds and related equipment were assessed in terms of safety, as well.ResultsOur findings show that more than 68% of playground equipment might create hazardous condition for kids. Lack of sustain maintenance for both of equipment and playground surface make some risky area for the mentioned group. Statistical analysis by SPSSWin 13 showed that more than 78 % of parents are worry about their child in terms of playground safetyproblems. Safety assessment of swings and slides showed that there are safety based problems in 89% of cases. Due to statistical reports of Tehran Emergency center, 10-12 and 8-10 year old kids suffer play based accident more than others. Reported traumas showed that face and skull and then feet suffered mechanical injury more than other limbs.ConclusionSurely, safety and health considerations are known as Municipality responsibilities, so for safety improvement in parks an integration safety system should be happened. HSE_MS seems a reliable approach for the mention goal. For improvement of exist parks and playground some related standard should be follows such as CPSC standards, EN 1176, and EN 1177. Also anthropometric data development

  6. A Study on Performance and Safety Tests of Defibrillator Equipment

    Directory of Open Access Journals (Sweden)

    Tavakoli Golpaygani A.

    2017-12-01

    Full Text Available Introduction: Nowadays, more than 10,000 different types of medical devices can be found in hospitals. This way, medical electrical equipment is being employed in a wide variety of fields in medical sciences with different physiological effects and measurements. Hospitals and medical centers must ensure that their critical medical devices are safe, accurate, reliable and operational at the required level of performance. Defibrillators are critical resuscitation devices. The use of reliable defibirillators has led to more effective treatments and improved patient safety through better control and management of complications during Cardiopulmonary Resuscitation (CPR. Materials and Methods: The metrological reliability of twenty frequent use, manual defibrillators in use ten hospitals (4 private and 6 public in one of the provinces of Iran according to international and national standards was evaluated. Results: Quantitative analysis of control and instrument accuracy showed the amount of the obtained results in many units are critical which had less value over the standard limitations especially in devices with poor battery. For the accuracy of delivered energy analysis, only twelve units delivered acceptable output values and the precision in the output energy measurements especialy in weak battry condition, after activation of discharge alarm, were low. Conclusion: Obtained results indicate a need for new and severe regulations on periodic performance verifications and medical equipment quality control program especially for high risk instruments. It is also necessary to provide training courses on the fundumentals of operation and performane parameters for medical staff in the field of meterology in medicine and how one can get good accuracy results especially in high risk medical devices.

  7. [Clinical safety audits for primary care centers. A pilot study].

    Science.gov (United States)

    Ruiz Sánchez, Míriam; Borrell-Carrió, Francisco; Ortodó Parra, Cristina; Fernàndez I Danés, Neus; Fité Gallego, Anna

    2013-01-01

    To identify organizational processes, violations of rules, or professional performances that pose clinical levels of insecurity. Descriptive cross-sectional survey with customized externally-behavioral verification and comparison of sources, conducted from June 2008 to February 2010. Thirteen of the 53 primary care teams (PCT) of the Catalonian Health Institute (ICS Costa de Ponent, Barcelona). Employees of 13 PCT classified into: director, nurse director, customer care administrators, and general practitioners. Non-random selection, teaching (TC)/non-teaching, urban (UC)/rural and small/large (LC) health care centers (HCC). A total of 33 indicators were evaluated; 15 of procedures, 9 of attitude, 3 of training, and 6 of communication. Level of uncertainty: <50% positive answers for each indicator. no collaboration. A total of 55 professionals participated (84.6% UC, 46.2% LC and 76.9% TC). Rank distribution: 13 customer care administrators, 13 nurse directors, 13 HCC directors, and 16 general practitioners. Levels of insecurity emerged from the following areas: reception of new medical professionals, injections administration, nursing weekend home calls, urgent consultations to specialists, aggressive patients, critical incidents over the agenda of the doctors, communication barriers with patients about treatment plans, and with immigrants. Clinical safety is on the agenda of the health centers. Identified areas of uncertainty are easily approachable, and are considered in the future system of accreditation of the Catalonian Government. General practitioners are more critical than directors, and teaching health care centers, rural and small HCC had a better sense of security. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  8. Food safety issues in China: a case study of the dairy sector.

    Science.gov (United States)

    Dong, Xiaoxia; Li, Zhemin

    2016-01-15

    Over the past 10 years, food safety incidents have occurred frequently in China. Food safety issues in the dairy sector have increasingly gained the attention of the Chinese government and the public. The objective of this research is to explore consumption changes of dairy products of different income groups after these dairy safety incidents. The research indicates that consumers' response to dairy safety risk is very intense. Dairy consumption has experienced a declining trend in recent years, and the impact of dairy safety incidents has lasted for at least 5 years. Until 2012, dairy consumption had not yet fully recovered from this influence. Using the random effects model, this study examined the relationship between food safety incident and consumption. Overall, the results show that consumers in the low-income group are more sensitive to safety risk than those in the high-income group. It can be seen from this paper that the decrease of urban residents' dairy consumption was mainly driven by changes in fresh milk consumption, while the decline of milk powder consumption, which was affected by the melamine incident, was relatively moderate, and milk powder consumption for the high-income group even increased. © 2015 Society of Chemical Industry.

  9. Forklift safety, traffic engineering and intelligent transport systems: a case study.

    Science.gov (United States)

    Horberry, Tim; Larsson, Tore J; Johnston, Ian; Lambert, John

    2004-11-01

    This paper details a forklift safety demonstration project undertaken at two manufacturing sites in Victoria, Australia. The purpose of the work was both to help improve safety at the two sites, and, more broadly, to develop, help implement and evaluate a series of human-centred design interventions involving vehicles and pedestrian workers. The 'before' and 'after' case study presented here summarises the background to the research and introduces the test sites. Thereafter, it describes the overall nature of the safety interventions proposed and introduces the methods developed to assess safety. For the traffic engineering interventions, positive safety results were found in terms of reductions in the number of potentially hazardous interactions involving forklifts. Similarly, for the vehicle interventions, the research found that forklift drivers and managers considered the newly developed and installed Intelligent Transport Systems to be broadly acceptable in operational conditions, and the systems' intended safety benefits were well understood. The results are discussed and conclusions are drawn regarding human factors aspects of forklift safety.

  10. Monitoring patient safety in primary care: an exploratory study using in-depth semistructured interviews.

    Science.gov (United States)

    Samra, Rajvinder; Bottle, Alex; Aylin, Paul

    2015-09-10

    To explore how information and data are used to monitor patient safety and quality of primary care by professionals working in, or supporting, primary healthcare. Qualitative study of semistructured interviews with a directed content analysis of transcripts. North-West London, UK. 21 individuals from various levels of the primary healthcare system were recruited, including general practitioners, practice nurses, practice managers, members of Clinical Commissioning Group (CCG) governing bodies, and senior members of regional patient safety teams. Participants described being overwhelmed with complicated data which lacked any meaningful analyses about safety and quality. There was also a lack of clarity over which patient safety events are expected to be reported or monitored. Participants also reported uncertainty on whose responsibility it was to act on patient safety information or concerns. At the practice level, there was a range of disincentives for responding to and acting on safety issues and concerns, with few reported benefits. Participants made recommendations to improve future monitoring. There is a need for clearer information in the form of specific guidelines, policies and procedures with regard to who monitors patient safety in primary care, what is monitored and how it should be monitored. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Studies on environment safety and application of advanced reactor for inland nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Wei, L.; Jie, L. [Nuclear Power Institute of China, Southwestern Nuclear Power Plants Prepatory Office (China)

    2014-07-01

    To study environment safety assessment of inland nuclear power plants (NPPs), the impact of environment safety under the normal operation was researched and the environment risk of serious accidents was analyzed. Moreover, the requirements and relevant provisions of site selection between international nuclear power plant and China's are comparatively studied. The conclusion was that the environment safety assessment of inland and coastal nuclear power plant have no essential difference; the advanced reactor can meet with high criteria of environment safety of inland nuclear power plants. In this way, China is safe and feasible to develop inland nuclear power plant. China's inland nuclear power plants will be as big market for advanced reactor. (author)

  12. Multimedia for occupational safety and health training: a pilot study examining a multimedia learning theory.

    Science.gov (United States)

    Wallen, Erik S; Mulloy, Karen B

    2006-10-01

    Occupational diseases are a significant problem affecting public health. Safety training is an important method of preventing occupational illness. Training is increasingly being delivered by computer although theories of learning from computer-based multimedia have been tested almost entirely on college students. This study was designed to determine whether these theories might also be applied to safety training applications for working adults. Participants viewed either computer-based multimedia respirator use training with concurrent narration, narration prior to the animation, or unrelated safety training. Participants then took a five-item transfer test which measured their ability to use their knowledge in new and creative ways. Participants who viewed the computer-based multimedia trainings both did significantly better than the control group on the transfer test. The results of this pilot study suggest that design guidelines developed for younger learners may be effective for training workers in occupational safety and health although more investigation is needed.

  13. Focus on the studies in support of fire safety analysis. IRSN modelling approach for nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Espargilliere, Julien; Meyrand, Raphael; Vinot, Thierry [Institut de Radioprotection et de Surete Nucleaire (IRSN), Fontenay-aux-Roses (France)

    2015-12-15

    For a fire safety analysis, in order to comply with nuclear safety goals, a nuclear fuel facility operator has to define the elements important for safety to be maintained, even in the case of a fire. One of the key points of this fire analysis is the assessment of possible fire scenarios in the facility. This paper presents the IRSN method applied to a case study to assess fire scenarios which have the most harmful effects on safety targets. The layout consists in a central room (fire cell) containing three glove boxes with radioactive material and three electrical cabinets. This room is linked to two connecting compartments (the fire cell and these two compartments define the containment cell) and then to two corridors. Each room is equipped with a mechanical ventilation system, and a pressure cascade is established from the corridors to the central room. A fire scenario was studied with fire ignition occurring in an electrical cabinet. This scenario has a set of safety goals (prevention of fire cell and containment device failure, propagation of the fire). This case study was conducted with the IRSN code SYLVIA based on two zones modelling. Safety goals were associated with key parameters and performance criteria to be fulfilled. Modelling assumptions were defined in order to maximize physical effects of the fire. Sensitivity studies were also conducted on key parameters such as oxygen limitation, equivalent-fuel definition. Eventually, a critical analysis of the code models was carried out.

  14. Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

    OpenAIRE

    Keller, Marla J.; Carpenter, Colleen A.; Yungtai Lo; Einstein, Mark H.; Congzhou Liu; David N Fredricks; Herold, Betsy C.

    2012-01-01

    Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety ...

  15. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine

    OpenAIRE

    Stohs, Sidney J.

    2017-01-01

    Citrus aurantium L. (bitter orange) extracts that contain p‐synephrine as the primary protoalkaloid are widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Questions have been raised about the safety of p‐synephrine because it has some structural similarity to ephedrine. This review focuses on current human, animal, in vitro, and mechanistic studies that address the safety, efficacy, and mechanisms of action of bitter or...

  16. Safety and efficacy of hysteroscopic sterilization compared with laparoscopic sterilization: an observational cohort study

    OpenAIRE

    Mao, Jialin; Pfeifer, Samantha; Schlegel, Peter; Sedrakyan, Art

    2015-01-01

    Objective To compare the safety and efficacy of hysteroscopic sterilization with the ?Essure? device with laparoscopic sterilization in a large, all-inclusive, state cohort. Design Population based cohort study. Settings Outpatient interventional setting in New York State. Participants Women undergoing interval sterilization procedure, including hysteroscopic sterilization with Essure device and laparoscopic surgery, between 2005 and 2013. Main outcomes measures Safety events within 30 days o...

  17. Statistical issues in the design, conduct and analysis of two large safety studies.

    Science.gov (United States)

    Gaffney, Michael

    2016-10-01

    The emergence, post approval, of serious medical events, which may be associated with the use of a particular drug or class of drugs, is an important public health and regulatory issue. The best method to address this issue is through a large, rigorously designed safety study. Therefore, it is important to elucidate the statistical issues involved in these large safety studies. Two such studies are PRECISION and EAGLES. PRECISION is the primary focus of this article. PRECISION is a non-inferiority design with a clinically relevant non-inferiority margin. Statistical issues in the design, conduct and analysis of PRECISION are discussed. Quantitative and clinical aspects of the selection of the composite primary endpoint, the determination and role of the non-inferiority margin in a large safety study and the intent-to-treat and modified intent-to-treat analyses in a non-inferiority safety study are shown. Protocol changes that were necessary during the conduct of PRECISION are discussed from a statistical perspective. Issues regarding the complex analysis and interpretation of the results of PRECISION are outlined. EAGLES is presented as a large, rigorously designed safety study when a non-inferiority margin was not able to be determined by a strong clinical/scientific method. In general, when a non-inferiority margin is not able to be determined, the width of the 95% confidence interval is a way to size the study and to assess the cost-benefit of relative trial size. A non-inferiority margin, when able to be determined by a strong scientific method, should be included in a large safety study. Although these studies could not be called "pragmatic," they are examples of best real-world designs to address safety and regulatory concerns. © The Author(s) 2016.

  18. Speaking up behaviours (safety voices) of healthcare workers: A metasynthesis of qualitative research studies.

    Science.gov (United States)

    Morrow, Kelly J; Gustavson, Allison M; Jones, Jacqueline

    2016-12-01

    A critical characteristic of effective teams in any setting is when each member is willing to speak up to share thoughts and ideas to improve processes. In spite of attempts by healthcare systems to encourage employees to speak up, employee silence remains a common cause of communication breakdowns, contributing to errors and suboptimal care delivery. Nurses in particular have reported low confidence in their communication abilities, and cite the belief that speaking up will not make a difference. To develop an understanding of how nurses and other healthcare workers relate to safety voice behaviors and how this might influence clinical practice. A search of the PubMed, CINAHL, and Academic Search Premier databases was conducted using keywords employee, nurse, qualitative, speak up, silence, safety, voice, and safety voice identified 372 articles with 11 retained after a review of the abstracts. Studies took place in Australia, Bulgaria, Canada, Hong Kong, East Africa, Ireland, Korea, New Zealand, Sweden, Switzerland, and the United States representing 504 healthcare workers including 354 nurses. This interpretive meta-synthesis of 11 qualitative articles published from 2005 to 2015 was conducted using a social constructivist approach with thematic analysis. The four themes identified are: 1) hierarchies and power dynamics negatively affect safety voice, 2) open communication is unsafe and ineffective, 3) embedded expectations of nurse behavior affect safety voice, and 4) nurse managers have a powerful positive or negative affect on safety voice. Healthcare workers worldwide report multiple social and hierarchy related fears surrounding the utilization of safety voice behaviors. Hesitance to speak up is pervasive among nurses, as is low self-efficacy related to safety voice. The presence of caring leaders, peer support, and an organizational commitment to safe, open cultures, may improve safety voice utilization among nurses and other healthcare workers. Copyright

  19. Nuclear safety in crisis regions

    Energy Technology Data Exchange (ETDEWEB)

    Ustohalova, Veronika; Englert, Matthias

    2017-04-12

    The use of nuclear energy demands extensive institutional and material infrastructure upon a foundation of stable intrastate conditions and interstate relations. Conflicts can result in catastrophic accidents, either deliberately or unintentionally. If there are nuclear facilities located in a crisis region, the risk of a nuclear disaster is markedly heightened. This can be explained not only in terms of the strategic relevance of the energy supply in military conflicts, but also the increased accident risks and hazards arising from collateral damage, as well as the erosion of the safety culture and institutional control in crisis regions with a nuclear infrastructure. Even just the escalation of a political dispute or the persistence of low intensity conflicts can make it generally more difficult and complex to maintain nuclear safety, if intrastate safety mechanisms come under strain or even fail as a result. So far no instance of military escalation, past or present, has led to an accident in a civil nuclear facility. Nevertheless, questions are clearly raised about the vulnerability of nuclear facilities in crisis regions and the risks associated with this vulnerability. Despite the potentially far-reaching consequences, too little attention is currently being paid to the linkage between intra- and interstate conflicts and the safety of nuclear facilities in crisis regions. The aim of the research presented here was to explore this theme and, after laying the groundwork in this manner, to raise awareness among policy-makers and the wider public. In this context the escalation of conflicts in the Ukraine is a particular focus. The first part of the report begins with a systematic look at the link between crisis regions and/or conflicts and nuclear safety. The various impact pathways relating to nuclear facility safety and the associated risks are described in relation to potential hazards induced by crises and wars. A nuclear facility can itself become a theatre

  20. A pilot phase I dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine.

    Science.gov (United States)

    Svensson, Tobias; Chowdhury, Onima; Garelius, Hege; Lorenz, Fryderyk; Saft, Leonie; Jacobsen, Sten-Eirik; Hellström-Lindberg, Eva; Cherif, Honar

    2014-11-01

    Thrombocytopenia is an independent adverse prognostic factor in patients with Myelodysplastic syndromes (MDS). Azacitidine, first-line treatment for the majority of patients with higher-risk MDS, is associated with aggravated thrombocytopenia during the first cycles. Eltrombopag is a novel thrombopoietin receptor agonist, which also has been shown to inhibit proliferation of leukaemia cell lines in vitro. This phase I clinical trial was designed to explore the safety and tolerability of combining eltrombopag with azacitidine in patients with MDS. In addition, we assessed the potential effects of eltrombopag on hematopoietic stem and progenitor cells (HSPCs) from included patients. Previously untreated patients with MDS eligible for treatment with azacitidine and with a platelet count <75 × 10(9) /L were included. Patients received eltrombopag in dose escalation cohorts during three cycles of azacitidine. Twelve patients, with a median age of 74 yr, were included. Severe adverse events included infectious complications, deep vein thrombosis and transient ischaemic attack. The maximal tolerated eltrombopag dose was 200 mg qd. Complete remission or bone marrow remission was achieved in 4 of 12 patients. Platelet counts improved or remained stable in 9 of 12 patients despite azacitidine treatment. No increase in blast count, disease progression, or bone marrow fibrosis related to study medication was reported. Eltrombopag did not induce cycling of HSPCs. The combination of eltrombopag with azacitidine in high-risk MDS patients is feasible and well tolerated. Improvements in platelet counts and the potential antileukaemic effect of eltrombopag should be explored in a randomised study. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Image guided dose escalated prostate radiotherapy: still room to improve

    Directory of Open Access Journals (Sweden)

    Milosevic Michael

    2009-11-01

    Full Text Available Abstract Background Prostate radiotherapy (RT dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT. The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG scoring scales. Methods From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT, mostly for high- or multiple risk factor intermediate-risk disease (n = 25. They received either 3-dimensional conformal RT (3DCRT, n = 226 or intensity modulated RT (IMRT including daily on-line IGRT with intraprostatic fiducial markers. Results Median follow-up was 67.8 months (range 24.4-84.7. There was no severe (grade 3-4 acute toxicity, and grade 2 acute gastrointestinal (GI toxicity was unusual (10.1%. The 5-year incidence of grade 2-3 late GI and genitourinary (GU toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018. Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively. Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147. Conclusion IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of

  2. Where is the pleasure in that? Low hedonic capacity predicts smoking onset and escalation.

    Science.gov (United States)

    Audrain-McGovern, Janet; Rodriguez, Daniel; Leventhal, Adam M; Cuevas, Jocelyn; Rodgers, Kelli; Sass, Joseph

    2012-10-01

    Hedonic capacity is a dispositional ability to experience pleasure in response to stimuli that are typically rewarding. The ability to derive pleasure from natural reinforcers has been relatively overlooked as a risk factor for adolescent smoking. The present study sought to provide initial evidence for a relationship between hedonic capacity and adolescent smoking onset and escalation. The sample was composed of 1,106 adolescents participating in a prospective longitudinal survey study of adolescent health behaviors. Variables were measured via self-report every 6 months for 4 waves of data spanning 18 months. We hypothesized that adolescents with lower hedonic capacity may be less responsive to natural reinforcers and therefore be prone to take up and rely on smoking as a reinforcer. A two-part latent growth curve model indicated that adolescents low in hedonic capacity were over two and a half times more likely to have smoked a cigarette in the past month at age 15.5 years (odds ratio = 2.64, 95% CI = 1.08-6.45) and to show a 90% increase (β = 0.9, z = 2.28, p = .02) in the rate of smoking escalation every 6 months across the following 18 months compared with adolescents with high hedonic capacity. This study provides the first evidence implicating hedonic capacity as a risk factor for adolescent smoking initiation and progression. Adolescents low in hedonic capacity may be an important population to target for smoking prevention and smoking cessation efforts possibly through behavioral skills to enhance pleasure derived through natural reinforcers.

  3. Factors that impact on the safety of patient handovers: An interview study

    DEFF Research Database (Denmark)

    Siemsen, Inger Margrete; Madsen, Marlene Dyrløv; Pedersen, Lene Funck

    2012-01-01

    Aims: Improvement of clinical handover is fundamental to meet the challenges of patient safety. The primary aim of this interview study is to explore healthcare professionals’ attitudes and experiences with critical episodes in patient handover in order to elucidate factors that impact on handover...... on patient safety in handover situations: communication, information, organisation, infrastructure, professionalism, responsibility, team awareness, and culture. Conclusions: The eight factors identified indicate that handovers are complex situations. The organisation did not see patient handover...... as a critical safety point of hospitalisation, revealing that the safety culture in regard to handover was immature. Work was done in silos and many of the handover barriers were seen to be related to the fact that only few had a full picture of a patient’s complete pathway....

  4. The snowball effect: friendship moderates escalations in depressed affect among avoidant and excluded children.

    Science.gov (United States)

    Bukowski, William M; Laursen, Brett; Hoza, Betsy

    2010-11-01

    A three-wave longitudinal study conducted with preadolescent boys and girls (N = 231 at Time 1 [T1]) was used to assess the hypotheses that aspects of social withdrawal would be predictors of a "snowball" cascade of depressed affect, and that friendship experiences would moderate these effects. Consistent with these hypotheses, multilevel modeling showed that measures of avoidance and exclusion at T1 were associated with concurrent levels of depressed affect and were antecedent to escalating trajectories of depressed affect over time. These accelerating growth curves fit a snowball cascade model. The analyses also showed the protective effects of friendship. Specifically, the snowball effect was limited to avoidant and excluded children who were friendless. Depressed affect did not increase among avoidant and excluded children who were friended.

  5. Burn injury-specific home safety assessment: a cross-sectional study in Iran.

    Directory of Open Access Journals (Sweden)

    Shahnam Arshi

    Full Text Available BACKGROUND: The aim of this study was to assess the feasibility of injury specific home safety investigation and to examine the home safety status focused on burn related safety in a rural population in the North-West of Iran. METHODS: A cross-sectional study was conducted on 265 rural households of rural Meshkinshahr, Iran. Cluster sampling method was used in 38 clusters with 7 households in each cluster. Clusters were selected on a probability proportional to size (PPS basis using the available health census database called D-Tarh. Data were analyzed using the statistical software package STATA 8. RESULTS: Possible risks were explored in fields of house structure; cooking and eating attitudes and behaviors; cooking appliances, specific appliances such as picnic gas burners, valors (traditional heaters, samovars (traditional water boilers, and air-heating appliances. Many safety concerns were explored needing to draw the attention of researchers and public health policy makers. CONCLUSION: Injury specific home safety surveys are useful and may provide useful information for safety promotion interventions.

  6. An observational study of child safety seat use in an international safe community: Tehran, Iran.

    Science.gov (United States)

    Moradi, Marziyeh; Khanjani, Narges; Nabipour, Amir Reza

    2017-01-02

    Despite strong evidence of the effectiveness of child safety seats in reducing injuries, the use of these devices in some communities is still rare. The purpose of this study was to determine the prevalence of child safety seat use and the factors influencing its use in the safe community of Tehran. This roadside observational study was conducted in 2015 and 2,178 personal cars with a child under 12 years aboard were observed on Tehran's streets in regard to use of child safety seats. Other variables such as the gender of the driver, driver's age group, type of street, region of municipality, time of day, and day of the week were also collected. Prevalence of child safety seat use was 4.3% and was significantly higher among women drivers, on freeways, and in municipal regions 1, 4, and 7. The prevalence of child safety seat use in Tehran as a most populous member of the international safe community was very low and most children commuted in insecure situations in the vehicle. Therefore, it is proposed that plans should be made to increase the use of child safety seats in international safe communities.

  7. Multi-sectoral action for child safety-a European study exploring implicated sectors.

    Science.gov (United States)

    Scholtes, Beatrice; Schröder-Bäck, Peter; Förster, Katharina; MacKay, Morag; Vincenten, Joanne; Brand, Helmut

    2017-06-01

    Injury to children in Europe, resulting in both death and disability, constitutes a significant burden on individuals, families and society. Inequalities between high and low-income countries are growing. The World Health Organisation Health 2020 strategy calls for inter-sectoral collaboration to address injury in Europe and advocates the whole of government and whole of society approaches to wicked problems. In this study we explore which sectors (e.g. health, transport, education) are relevant for four domains of child safety (intentional injury, water, road and home safety). We used the organigraph methodology, originally developed to demonstrate how organizations work, to describe the governance of child safety interventions. Members of the European Child Safety Alliance, working in the field of child safety in 24 European countries, drew organigraphs of evidence-based interventions. They included the different actors involved and the processes between them. We analyzed the organigraphs by counting the actors presented and categorizing them into sectors using a pre-defined analysis framework. We received 44 organigraphs from participants in 24 countries. Twenty-seven sectors were identified across the four domains. Nine of the 27 identified sectors were classified as 'core sectors' (education, health, home affairs, justice, media, recreation, research, social/welfare services and consumers). This study reveals the multi-sectoral nature of child safety in practice. It provides information for stakeholders working in child safety to help them implement inter-sectoral child safety interventions taking a whole-of-government and whole-of-society approach to health governance.

  8. Safety profile of Hoodia gordonii extract: Rabbit prenatal developmental toxicity study

    NARCIS (Netherlands)

    Dent, M.P.; Wolterbeek, A.P.M.; Russell, P.J.; Bradford, R.

    2012-01-01

    Hoodia gordonii extract was orally administered by gavage to groups of 22 female New Zealand white rabbits from day 3-28 after mating at doses of 0 (control), 3, 6 or 12. mg/kg bodyweight/day. These doses were reached by a dose escalation phase between days 3 and 7 after mating. As well as a vehicle

  9. Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

    Science.gov (United States)

    LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

    2013-01-01

    Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

  10. Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study

    OpenAIRE

    Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F.; Shara, Nawar M.; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

    2015-01-01

    Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day ...

  11. Destined to die but not to wage war: how existential threat can contribute to escalation or de-escalation of violent intergroup conflict.

    Science.gov (United States)

    Jonas, Eva; Fritsche, Immo

    2013-10-01

    War means threat to people's lives. Research derived from terror management theory (TMT) illustrates that the awareness of death leads people to defend cultural ingroups and their worldviews to attain a sense of symbolic immortality and thereby buffer existential anxiety. This can result in hostile effects of mortality salience (MS), such as derogation of outgroup members, prejudice, stereotyping, aggression, and racism, which, in turn, can lead to the escalation of violent intergroup conflict and, thus, the escalation of war. Yet, escalation of destructive conflict following MS is not automatic. Instead, research on TMT suggests that MS does not necessarily result in conflict and intolerance but can also foster positive tendencies, such as intergroup fairness or approval of pacifism, depending on how existential threat is perceived, whether the need for symbolic self-transcendence is satisfied, which social norms are salient, and how social situations are interpreted. In the present article, we review current TMT research with the aim of reconciling the seemingly contradictory findings of hostile and peaceful reactions to reminders of death. We present a terror management model of escalation and de-escalation of violent intergroup conflicts, which takes into account the interaction between threat salience and features of the social situation. We also discuss possible intervention strategies to override detrimental consequences of existential threat and argue that war is not the inevitable consequence of threat. PsycINFO Database Record (c) 2013 APA, all rights reserved

  12. Fossil evidence for Cretaceous escalation in angiosperm leaf vein evolution.

    Science.gov (United States)

    Feild, Taylor S; Brodribb, Timothy J; Iglesias, Ari; Chatelet, David S; Baresch, Andres; Upchurch, Garland R; Gomez, Bernard; Mohr, Barbara A R; Coiffard, Clement; Kvacek, Jiri; Jaramillo, Carlos

    2011-05-17

    The flowering plants that dominate modern vegetation possess leaf gas exchange potentials that far exceed those of all other living or extinct plants. The great divide in maximal ability to exchange CO(2) for water between leaves of nonangiosperms and angiosperms forms the mechanistic foundation for speculation about how angiosperms drove sweeping ecological and biogeochemical change during the Cretaceous. However, there is no empirical evidence that angiosperms evolved highly photosynthetically active leaves during the Cretaceous. Using vein density (D(V)) measurements of fossil angiosperm leaves, we show that the leaf hydraulic capacities of angiosperms escalated several-fold during the Cretaceous. During the first 30 million years of angiosperm leaf evolution, angiosperm leaves exhibited uniformly low vein D(V) that overlapped the D(V) range of dominant Early Cretaceous ferns and gymnosperms. Fossil angiosperm vein densities reveal a subsequent biphasic increase in D(V). During the first mid-Cretaceous surge, angiosperm D(V) first surpassed the upper bound of D(V) limits for nonangiosperms. However, the upper limits of D(V) typical of modern megathermal rainforest trees first appear during a second wave of increased D(V) during the Cretaceous-Tertiary transition. Thus, our findings provide fossil evidence for the hypothesis that significant ecosystem change brought about by angiosperms lagged behind the Early Cretaceous taxonomic diversification of angiosperms.

  13. Attention modulates adaptive motor learning in the 'broken escalator' paradigm.

    Science.gov (United States)

    Patel, Mitesh; Kaski, Diego; Bronstein, Adolfo M

    2014-07-01

    The physical stumble caused by stepping onto a stationary (broken) escalator represents a locomotor aftereffect (LAE) that attests to a process of adaptive motor learning. Whether such learning is primarily explicit (requiring attention resources) or implicit (independent of attention) is unknown. To address this question, we diverted attention in the adaptation (MOVING) and aftereffect (AFTER) phases of the LAE by loading these phases with a secondary cognitive task (sequential naming of a vegetable, fruit and a colour). Thirty-six healthy adults were randomly assigned to 3 equally sized groups. They performed 5 trials stepping onto a stationary sled (BEFORE), 5 with the sled moving (MOVING) and 5 with the sled stationary again (AFTER). A 'Dual-Task-MOVING (DTM)' group performed the dual-task in the MOVING phase and the 'Dual-Task-AFTEREFFECT (DTAE)' group in the AFTER phase. The 'control' group performed no dual task. We recorded trunk displacement, gait velocity and gastrocnemius muscle EMG of the left (leading) leg. The DTM, but not the DTAE group, had larger trunk displacement during the MOVING phase, and a smaller trunk displacement aftereffect compared with controls. Gait velocity was unaffected by the secondary cognitive task in either group. Thus, adaptive locomotor learning involves explicit learning, whereas the expression of the aftereffect is automatic (implicit). During rehabilitation, patients should be actively encouraged to maintain maximal attention when learning new or challenging locomotor tasks.

  14. Patient safety culture in China: a case study in an outpatient setting in Beijing.

    Science.gov (United States)

    Liu, Chaojie; Liu, Weiwei; Wang, Yuanyuan; Zhang, Zhihong; Wang, Peng

    2014-07-01

    To investigate the patient safety culture in an outpatient setting in Beijing and explore the meaning and implications of the safety culture from the perspective of health workers and patients. A mixed methods approach involving a questionnaire survey and in-depth interviews was adopted. Among the 410 invited staff members, 318 completed the Hospital Survey of Patient Safety Culture (HSOPC). Patient safety culture was described using 12 subscale scores. Inter-subscale correlation analysis, ANOVA and stepwise multivariate regression analyses were performed to identify the determinants of the patient safety culture scores. Interviewees included 22 patients selected through opportunity sampling and 27 staff members selected through purposive sampling. The interview data were analysed thematically. The survey respondents perceived high levels of unsafe care but had personally reported few events. Lack of 'communication openness' was identified as a major safety culture problem, and a perception of 'penalty' was the greatest barrier to the encouragement of error reporting. Cohesive 'teamwork within units', while found to be an area of strength, conversely served as a protective and defensive mechanism for medical practice. Low levels of trust between providers and consumers and lack of management support constituted an obstacle to building a positive patient safety culture. This study in China demonstrates that a punitive approach to error is still widespread despite increasing awareness of unsafe care, and managers have been slow in acknowledging the importance of building a positive patient safety culture. Strong 'teamwork within units', a common area of strength, could fuel the concealment of errors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Patient safety in primary care has many aspects: an interview study in primary care doctors and nurses.

    NARCIS (Netherlands)

    Gaal, S.; Laarhoven, E. van; Wolters, R.J.; Wetzels, R.; Verstappen, W.H.J.M.; Wensing, M.J.P.

    2010-01-01

    RATIONALE, AIMS AND OBJECTIVES: Scientific definitions of patient safety may be difficult to apply in routine health care delivery. It is unknown what primary care workers consider patient safety. This study aimed to clarify the concept of patient safety in primary care. METHODS: We held 29

  16. Monitoring safety in a phase III real-world effectiveness trial: use of novel methodology in the Salford Lung Study.

    Science.gov (United States)

    Collier, Sue; Harvey, Catherine; Brewster, Jill; Bakerly, Nawar Diar; Elkhenini, Hanaa F; Stanciu, Roxana; Williams, Claire; Brereton, Jacqui; New, John P; McCrae, John; McCorkindale, Sheila; Leather, David

    2017-03-01

    The Salford Lung Study (SLS) programme, encompassing two phase III pragmatic randomised controlled trials, was designed to generate evidence on the effectiveness of a once-daily treatment for asthma and chronic obstructive pulmonary disease in routine primary care using electronic health records. The objective of this study was to describe and discuss the safety monitoring methodology and the challenges associated with ensuring patient safety in the SLS. Refinements to safety monitoring processes and infrastructure are also discussed. The study results are outside the remit of this paper. The results of the COPD study were published recently and a more in-depth exploration of the safety results will be the subject of future publications. The SLS used a linked database system to capture relevant data from primary care practices in Salford and South Manchester, two university hospitals and other national databases. Patient data were collated and analysed to create daily summaries that were used to alert a specialist safety team to potential safety events. Clinical research teams at participating general practitioner sites and pharmacies also captured safety events during routine consultations. Confidence in the safety monitoring processes over time allowed the methodology to be refined and streamlined without compromising patient safety or the timely collection of data. The information technology infrastructure also allowed additional details of safety information to be collected. Integration of multiple data sources in the SLS may provide more comprehensive safety information than usually collected in standard randomised controlled trials. Application of the principles of safety monitoring methodology from the SLS could facilitate safety monitoring processes for future pragmatic randomised controlled trials and yield important complementary safety and effectiveness data. © 2016 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

  17. Road safety effects of porous asphalt: a systematic review of evaluation studies

    DEFF Research Database (Denmark)

    Elvik, R.; Greibe, Poul

    2005-01-01

    This paper presents a systematic review of studies that have evaluated the effects on road safety of porous asphalt. Porous asphalt is widely used on motorways in Europe, mainly in order to reduce traffic noise and increase road capacity. A meta-analysis was made of six studies, containing a total...... of eighteen estimates of the effect of porous asphalt on accident rates. No clear effect on road safety of porous asphalt was found. All summary estimates of effect indicated very small changes in accident rates and very few were statistically significant at conventional levels. Studies that have evaluated...... of these changes in risk factors on accident occurrence cannot be predicted. On the whole, the research that has been reported so far regarding road safety effects of porous asphalt is inconclusive. The studies are not of high quality and the findings are inconsistent....

  18. A study on the safety regulation of byproduct material (II)

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jong Sun; Song, Yang Su [Chosun Univ., Gwangju (Korea, Republic of)

    2000-03-15

    The scope of this study consists of : in relating to the domestic license of byproduct material, a survey of technical criteria and status of regulation in U.S.A., a determination of range of application and contents of byproduct material, a tentative suggestion of related technical criteria and regulatory system. A study was performed about the above topics to establish the safe regulation of byproduct material institutionally, and this can be contributed in establishing the proper domestic technical criteria related.

  19. Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone.

    Science.gov (United States)

    Norman, Kevin J; Seiden, Jacob A; Klickstein, Jacob A; Han, Xiao; Hwa, Lara S; DeBold, Joseph F; Miczek, Klaus A

    2015-03-01

    Stress experiences have been shown to be a risk factor for alcohol abuse in humans; however, a reliable mouse model using episodic social stress has yet to be developed. The current studies investigated the effects of mild and moderate social defeat protocols on plasma corticosterone, voluntary alcohol drinking, and motivation to drink alcohol. Outbred Carworth Farms Webster (CFW) mice were socially defeated for 10 days during which the intruder mouse underwent mild (15 bites: mean = 1.5 min) or moderate (30 bites: mean = 3.8 min) stress. Plasma corticosterone was measured on days 1 and 10 of the defeat. Ethanol drinking during continuous access to alcohol was measured 10 days following the defeat or 10 days prior to, during, and 20 days after the defeat. Motivation to drink was determined using a progressive ratio (PR) operant conditioning schedule during intermittent access to alcohol. Plasma corticosterone was elevated in both stress groups on days 1 and 10. Ethanol consumption and preference following moderate stress were higher (13.3 g/kg/day intake) than both the mild stress group (8.0 g/kg/day) and controls (7.4 g/kg/day). Mice with previously acquired ethanol drinking showed decreased alcohol consumption during the moderate stress followed by an increase 20 days post-defeat. Moderately stressed mice also showed escalated ethanol intake and self-administration during a schedule of intermittent access to alcohol. Social defeat experiences of moderate intensity and duration led to increased ethanol drinking and preference in CFW mice. Ongoing work investigates the interaction between glucocorticoids and dopaminergic systems as neural mechanisms for stress-escalated alcohol consumption.

  20. Family initiated escalation of care for the deteriorating patient in hospital: Family centred care or just "box ticking".

    Science.gov (United States)

    Gill, Fenella J; Leslie, Gavin D; Marshall, Andrea P

    2016-11-01

    Family centred care is a shared belief that a child's emotional and developmental needs are best met when the health system involves the family in planning, delivery and evaluation of care. The important role that families contribute to health care outcomes is emphasised throughout the National Safety and Quality Healthcare Service (NSQHS) Standards. An emerging component is the family's contribution to Rapid Response Systems (RRS) through the early detection of patient clinical deterioration. This initiative has been driven, in part, by a number of high profile paediatric cases where it was identified that healthcare providers did not appropriately respond to families' concerns, resulting in patient deaths. This paper draws together the synergies between family centred care concepts, the NSQHS Standards, and the progress made to date in developing a family initiated process for escalating care with specific reference to paediatric acute care. A number of programs have been developed to guide implementation of family escalation of care. Measures of effectiveness of implementation have mainly focused on policy and process without first understanding barriers or facilitators through engagement with stakeholders and environmental assessment. Two recent reviews have not identified any rigorous attempts to evaluate implementation and only 11 reports are cited across these