Central safety factor and β N control on NSTX-U via beam power and plasma boundary shape modification, using TRANSP for closed loop simulations

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

Boyer, M. D.; Andre, R.; Gates, D. A.

The high-performance operational goals of NSTX-U will require development of advanced feedback control algorithms, including control of ßN and the safety factor profile. In this work, a novel approach to simultaneously controlling ßN and the value of the safety factor on the magnetic axis, q0, through manipulation of the plasma boundary shape and total beam power, is proposed. Simulations of the proposed scheme show promising results and motivate future experimental implementation and eventual integration into a more complex current profile control scheme planned to include actuation of individual beam powers, density, and loop voltage. As part of this work, amore » flexible framework for closed loop simulations within the high-fidelity code TRANSP was developed. The framework, used here to identify control-design-oriented models and to tune and test the proposed controller, exploits many of the predictive capabilities of TRANSP and provides a means for performing control calculations based on user-supplied data (controller matrices, target waveforms, etc.). The flexible framework should enable high-fidelity testing of a variety of control algorithms, thereby reducing the amount of expensive experimental time needed to implement new control algorithms on NSTX-U and other devices.« less

Central safety factor and βN control on NSTX-U via beam power and plasma boundary shape modification, using TRANSP for closed loop simulations

NASA Astrophysics Data System (ADS)

Boyer, M. D.; Andre, R.; Gates, D. A.; Gerhardt, S.; Goumiri, I. R.; Menard, J.

2015-05-01

The high-performance operational goals of NSTX-U will require development of advanced feedback control algorithms, including control of βN and the safety factor profile. In this work, a novel approach to simultaneously controlling βN and the value of the safety factor on the magnetic axis, q0, through manipulation of the plasma boundary shape and total beam power, is proposed. Simulations of the proposed scheme show promising results and motivate future experimental implementation and eventual integration into a more complex current profile control scheme planned to include actuation of individual beam powers, density, and loop voltage. As part of this work, a flexible framework for closed loop simulations within the high-fidelity code TRANSP was developed. The framework, used here to identify control-design-oriented models and to tune and test the proposed controller, exploits many of the predictive capabilities of TRANSP and provides a means for performing control calculations based on user-supplied data (controller matrices, target waveforms, etc). The flexible framework should enable high-fidelity testing of a variety of control algorithms, thereby reducing the amount of expensive experimental time needed to implement new control algorithms on NSTX-U and other devices.

Sensitivity of magnetic field-line pitch angle measurements to sawtooth events in tokamaks

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

Ko, J., E-mail: jinseok@nfri.re.kr

2016-11-15

The sensitivity of the pitch angle profiles measured by the motional Stark effect (MSE) diagnostic to the evolution of the safety factor, q, profiles during the tokamak sawtooth events has been investigated for Korea Superconducting Tokamak Advanced Research (KSTAR). An analytic relation between the tokamak pitch angle, γ, and q estimates that Δγ ∼ 0.1° is required for detecting Δq ∼ 0.05 near the magnetic axis (not at the magnetic axis, though). The pitch angle becomes less sensitive to the same Δq for the middle and outer regions of the plasma (Δγ ∼ 0.5°). At the magnetic axis, it ismore » not straightforward to directly relate the γ sensitivity to Δq since the gradient of γ(R), where R is the major radius of the tokamak, is involved. Many of the MSE data obtained from the 2015 KSTAR campaign, when calibrated carefully, can meet these requirements with the time integration down to 10 ms. The analysis with the measured data shows that the pitch angle profiles and their gradients near the magnetic axis can resolve the change of the q profiles including the central safety factor, q{sub 0}, during the sawtooth events.« less

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme.

PubMed

Holz, Frank G; Bandello, Francesco; Gillies, Mark; Mitchell, Paul; Osborne, Aaron; Sheidow, Tom; Souied, Eric; Figueroa, Marta S

2013-09-01

Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. The LUMINOUS programme comprises a prospective observational study assessing ranibizumab 'real-world' safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0-0.5%). Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in 'real-life' settings. The 5-year LUMINOUS prospective observational study will address this need.

Safety of ranibizumab in routine clinical practice: 1-year retrospective pooled analysis of four European neovascular AMD registries within the LUMINOUS programme

PubMed Central

Holz, Frank G; Bandello, Francesco; Gillies, Mark; Mitchell, Paul; Osborne, Aaron; Sheidow, Tom; Souied, Eric; Figueroa, Marta S

2013-01-01

Purpose Evaluation of 1-year safety profile of intravitreal ranibizumab 0.5 mg in neovascular age-related macular degeneration (NV-AMD) within routine clinical practice. Methods The LUMINOUS programme comprises a prospective observational study assessing ranibizumab ‘real-world’ safety and clinical effectiveness across licensed indications worldwide and an annual retrospective pooled safety analysis from completed NV-AMD ranibizumab registries. 1-year data from four European registries are available. This retrospective pooled safety analysis assessed 1-year incidence rates for safety events of particular interest (key ocular or systemic events possibly related to the injection procedure or vascular endothelial growth factor inhibition) together with treatment exposure. Patients were treated according to local protocols within the ranibizumab licence. Results Data of 4444 patients from registries in Germany (n=3470), the Netherlands (n=243), Belgium (n=260) and Sweden (n=471) were retrospectively pooled. Between 70.4% and 84.4% of enrolled patients completed 1 year of follow-up. Most frequent overall ocular events of particular interest were retinal pigment epithelial tears (27 patients; <1%) and intraocular pressure-related events (12 patients; <0.3%). Most frequent non-ocular event of particular interest was stroke (19 patients; 0.4%); annual incidence of stroke was low across all registries (0.0–0.5%). Conclusions Ranibizumab demonstrated favourable 1-year safety profile for NV-AMD in this routine clinical practice sample, consistent with previous reported trial data. Additional data from a larger patient population are needed to better describe the long-term safety profile of ranibizumab in routine clinical practice and further evaluate risk for infrequent but serious events in ‘real-life’ settings. The 5-year LUMINOUS prospective observational study will address this need. PMID:23850682

Off-axis current drive and real-time control of current profile in JT-60U

NASA Astrophysics Data System (ADS)

Suzuki, T.; Ide, S.; Oikawa, T.; Fujita, T.; Ishikawa, M.; Seki, M.; Matsunaga, G.; Hatae, T.; Naito, O.; Hamamatsu, K.; Sueoka, M.; Hosoyama, H.; Nakazato, M.; JT-60 Team

2008-04-01

Aiming at optimization of current profile in high-β plasmas for higher confinement and stability, a real-time control system of the minimum of the safety factor (qmin) using the off-axis current drive has been developed. The off-axis current drive can raise the safety factor in the centre and help to avoid instability that limits the performance of the plasma. The system controls the injection power of lower-hybrid waves, and hence its off-axis driven current in order to control qmin. The real-time control of qmin is demonstrated in a high-β plasma, where qmin follows the temporally changing reference qmin,ref from 1.3 to 1.7. Applying the control to another high-β discharge (βN = 1.7, βp = 1.5) with m/n = 2/1 neo-classical tearing mode (NTM), qmin was raised above 2 and the NTM was suppressed. The stored energy increased by 16% with the NTM suppressed, since the resonant rational surface was eliminated. For the future use for current profile control, current density profile for off-axis neutral beam current drive (NBCD) is for the first time measured, using the motional Stark effect diagnostic. Spatially localized NBCD profile was clearly observed at the normalized minor radius ρ of about 0.6-0.8. The location was also confirmed by multi-chordal neutron emission profile measurement. The total amount of the measured beam driven current was consistent with the theoretical calculation using the ACCOME code. The CD location in the calculation was inward shifted than the measurement.

Patient safety climate profiles across time: Strength and level of safety climate associated with a quality improvement program in Switzerland-A cross-sectional survey study.

PubMed

Mascherek, Anna C; Schwappach, David L B

2017-01-01

Safety Climate has been acknowledged as an unspecific factor influencing patient safety. However, studies rarely provide in-depth analysis of climate data. As a helpful approach, the concept of "climate strength" has been proposed. In the present study we tested the hypotheses that even if safety climate remains stable on mean-level across time, differences might be evident in strength or shape. The data of two hospitals participating in a large national quality improvement program were analysed for differences in climate profiles at two measurement occasions. We analysed differences on mean-level, differences in percent problematic response, agreement within groups, and frequency histograms in two large hospitals in Switzerland at two measurement occasions (2013 and 2015) applying the Safety Climate Survey. In total, survey responses of 1193 individuals were included in the analyses. Overall, small but significant differences on mean-level of safety climate emerged for some subgroups. Also, although agreement was strong at both time-points within groups, tendencies of divergence or consensus were present in both hospitals. Depending on subgroup and analyses chosen, differences were more or less pronounced. The present study illustrated that taking several measures into account and describing safety climate from different perspectives is necessary in order to fully understand differences and trends within groups and to develop interventions addressing the needs of different groups more precisely.

Observation of instability-induced current redistribution in a spherical-torus plasma.

PubMed

Menard, J E; Bell, R E; Gates, D A; Kaye, S M; LeBlanc, B P; Levinton, F M; Medley, S S; Sabbagh, S A; Stutman, D; Tritz, K; Yuh, H

2006-09-01

A motional Stark effect diagnostic has been utilized to reconstruct the parallel current density profile in a spherical-torus plasma for the first time. The measured current profile compares favorably with neoclassical theory when no large-scale magnetohydrodynamic instabilities are present in the plasma. However, a current profile anomaly is observed during saturated interchange-type instability activity. This apparent anomaly can be explained by redistribution of neutral beam injection current drive and represents the first observation of interchange-type instabilities causing such redistribution. The associated current profile modifications contribute to sustaining the central safety factor above unity for over five resistive diffusion times, and similar processes may contribute to improved operational scenarios proposed for ITER.

Driver behaviour profiles for road safety analysis.

PubMed

Ellison, Adrian B; Greaves, Stephen P; Bliemer, Michiel C J

2015-03-01

Driver behaviour is a contributing factor in over 90 percent of road crashes. As a consequence, there is significant benefit in identifying drivers who engage in unsafe driving practices. Driver behaviour profiles (DBPs) are introduced here as an approach for evaluating driver behaviour as a function of the risk of a casualty crash. They employ data collected using global positioning system (GPS) devices, supplemented with spatiotemporal information. These profiles are comprised of common risk scores that can be used to compare drivers between each other and across time and space. The paper details the development of these DBPs and demonstrates their use as an input into modelling the factors that influence driver behaviour. The results show that even having controlled for the influence of the road environment, these factors remain the strongest predictors of driver behaviour suggesting different spatiotemporal environments elicit a variety of psychological responses in drivers. The approach and outcomes will be of interest to insurance companies in enhancing the risk-profiling of drivers with on-road driving and government through assessing the impacts of behaviour-change interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Risk Assessment Terminology: Risk Communication Part 2

PubMed Central

Bentley, Stefano; Giacometti, Federica; Piva, Silvia; Serraino, Andrea

2016-01-01

The paper describes the terminology of risk communication in the view of food safety: different aspects of risk perception (perceived risk, media triggers, the psychometric paradigm, fright factors and cultural determinants of risk perception) are described. The risk profile elements are illustrated in the manuscript: hazard-food commodity combination(s) of concern; description of the public health problem; food production, processing, distribution and consumption; needs and questions for the risk assessors; available information and major knowledge gaps and other risk profile elements. PMID:27800443

Topical retinoids in acne vulgaris: update on efficacy and safety.

PubMed

Thielitz, Anja; Gollnick, Harald

2008-01-01

Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe. Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.

Patient safety climate profiles across time: Strength and level of safety climate associated with a quality improvement program in Switzerland—A cross-sectional survey study

PubMed Central

Mascherek, Anna C.

2017-01-01

Safety Climate has been acknowledged as an unspecific factor influencing patient safety. However, studies rarely provide in-depth analysis of climate data. As a helpful approach, the concept of “climate strength” has been proposed. In the present study we tested the hypotheses that even if safety climate remains stable on mean-level across time, differences might be evident in strength or shape. The data of two hospitals participating in a large national quality improvement program were analysed for differences in climate profiles at two measurement occasions. We analysed differences on mean-level, differences in percent problematic response, agreement within groups, and frequency histograms in two large hospitals in Switzerland at two measurement occasions (2013 and 2015) applying the Safety Climate Survey. In total, survey responses of 1193 individuals were included in the analyses. Overall, small but significant differences on mean-level of safety climate emerged for some subgroups. Also, although agreement was strong at both time-points within groups, tendencies of divergence or consensus were present in both hospitals. Depending on subgroup and analyses chosen, differences were more or less pronounced. The present study illustrated that taking several measures into account and describing safety climate from different perspectives is necessary in order to fully understand differences and trends within groups and to develop interventions addressing the needs of different groups more precisely. PMID:28753633

Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

PubMed

Persson, Mikael; Hornberg, Jorrit J

2016-12-19

High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

Evaluation of the in-service safety performance of safety-shape and vertical concrete barriers.

DOT National Transportation Integrated Search

2011-12-16

Roadside concrete barriers have been widely used to protect errant motorists from hitting : roadside hazards or obstacles. Two concrete barrier profiles, vertical and safety-shape, have been used : for this purpose. The safety-shape profile has been ...

Tramadol can selectively manage moderate pain in children following European advice limiting codeine use.

PubMed

Marzuillo, Pierluigi; Calligaris, Lorenzo; Barbi, Egidio

2014-11-01

The European Medicine Agency recommendations limiting codeine use in children have created a void in managing moderate pain. We review the evidence on the pharmacokinetic, pharmacodynamic and safety profile of tramadol, a possible substitute for codeine. Tramadol appears to be safe in both paediatric inpatients and outpatients. It may be appropriate to limit the current use of tramadol to monitored settings in children with risk factors for respiratory depression, subject to further safety evidence. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

A review on adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in nonsmall cell lung cancer patients.

PubMed

Biswas, B; Ghadyalpatil, N; Krishna, M V; Deshmukh, J

2017-12-01

The epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of EGFR-mutant nonsmall cell lung cancer (NSCLC). These EGFR TKIs demonstrate a different adverse event (AE) profile as compared to conventional chemotherapy agents. They are more commonly associated with cutaneous AEs and diarrhea while hematological AEs occurred commonly with chemotherapy agents. These AEs are the extension of pharmacological effect and occur as a result of blockade of EGFR-regulated pathways in the skin and gastrointestinal tract. This review article sheds light on the safety profile of first-, second-, and third-generation EGFR TKIs based on data obtained from several clinical trials conducted in NSCLC patients and highlights trials comparing these agents with the conventional chemotherapy agents. The strategies to manage EGFR TKI-related AEs are also reviewed.

Suppression of MHD fluctuations leading to improved confinement in a gun-driven spheromak.

PubMed

McLean, H S; Woodruff, S; Hooper, E B; Bulmer, R H; Hill, D N; Holcomb, C; Moller, J; Stallard, B W; Wood, R D; Wang, Z

2002-03-25

Magnetic fluctuations have been reduced to approximately 1% during discharges on the Sustained Spheromak Physics Experiment by shaping the spatial distribution of the bias magnetic flux in the device. In the resulting quiescent regime, the safety factor profile is nearly flat in the plasma and the dominant ideal and resistive MHD modes are greatly reduced. During this period, the temperature profile is peaked at the magnetic axis and maps onto magnetic flux contours. Energy confinement time is improved over previous reports in a driven spheromak.

Development of a Quality and Safety Competency Curriculum for Radiation Oncology Residency: An International Delphi Study.

PubMed

Adleman, Jenna; Gillan, Caitlin; Caissie, Amanda; Davis, Carol-Anne; Liszewski, Brian; McNiven, Andrea; Giuliani, Meredith

2017-06-01

To develop an entry-to-practice quality and safety competency profile for radiation oncology residency. A comprehensive list of potential quality and safety competency items was generated from public and professional resources and interprofessional focus groups. Redundant or out-of-scope items were eliminated through investigator consensus. Remaining items were subjected to an international 2-round modified Delphi process involving experts in radiation oncology, radiation therapy, and medical physics. During Round 1, each item was scored independently on a 9-point Likert scale indicating appropriateness for inclusion in the competency profile. Items indistinctly ranked for inclusion or exclusion were re-evaluated through web conference discussion and reranked in Round 2. An initial 1211 items were compiled from 32 international sources and distilled to 105 unique potential quality and safety competency items. Fifteen of the 50 invited experts participated in round 1: 10 radiation oncologists, 4 radiation therapists, and 1 medical physicist from 13 centers in 5 countries. Round 1 rankings resulted in 80 items included, 1 item excluded, and 24 items indeterminate. Two areas emerged more prominently within the latter group: change management and human factors. Web conference with 5 participants resulted in 9 of these 24 items edited for content or clarity. In Round 2, 12 participants rescored all indeterminate items resulting in 10 items ranked for inclusion. The final 90 enabling competency items were organized into thematic groups consisting of 18 key competencies under headings adapted from Deming's System of Profound Knowledge. This quality and safety competency profile may inform minimum training standards for radiation oncology residency programs. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a Quality and Safety Competency Curriculum for Radiation Oncology Residency: An International Delphi Study

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

Adleman, Jenna; Gillan, Caitlin; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario

Purpose: To develop an entry-to-practice quality and safety competency profile for radiation oncology residency. Methods and Materials: A comprehensive list of potential quality and safety competency items was generated from public and professional resources and interprofessional focus groups. Redundant or out-of-scope items were eliminated through investigator consensus. Remaining items were subjected to an international 2-round modified Delphi process involving experts in radiation oncology, radiation therapy, and medical physics. During Round 1, each item was scored independently on a 9-point Likert scale indicating appropriateness for inclusion in the competency profile. Items indistinctly ranked for inclusion or exclusion were re-evaluated through webmore » conference discussion and reranked in Round 2. Results: An initial 1211 items were compiled from 32 international sources and distilled to 105 unique potential quality and safety competency items. Fifteen of the 50 invited experts participated in round 1: 10 radiation oncologists, 4 radiation therapists, and 1 medical physicist from 13 centers in 5 countries. Round 1 rankings resulted in 80 items included, 1 item excluded, and 24 items indeterminate. Two areas emerged more prominently within the latter group: change management and human factors. Web conference with 5 participants resulted in 9 of these 24 items edited for content or clarity. In Round 2, 12 participants rescored all indeterminate items resulting in 10 items ranked for inclusion. The final 90 enabling competency items were organized into thematic groups consisting of 18 key competencies under headings adapted from Deming's System of Profound Knowledge. Conclusions: This quality and safety competency profile may inform minimum training standards for radiation oncology residency programs.« less

Safety of topical minoxidil solution: a one-year, prospective, observational study.

PubMed

Shapiro, Jerry

2003-01-01

Topical minoxidil solution (TMS) is widely used for androgenetic alopecia (AGA), and this is the first report of a large safety trial. The aim of the study was to evaluate the safety profile of TMS by comparing hospitalization and death rates among subjects using TMS with controls. Cardiovascular safety and pregnancy outcomes were evaluated, and usage patterns were described. All subjects were followed at baseline, 3, 6, 9, and 12 months. Usage patterns, pregnancy status, overnight hospital stays, and cardiovascular risk factors were evaluated. Subjects rated effectiveness of TMS in the treatment of AGA. Statistical analyses were conducted to determine if TMS was associated with an increased risk of death or hospitalization. TMS is a safe and effective treatment for AGA. There were no increases in cardiovascular events and no apparent increased risk for adverse pregnancy outcomes. This large, prospective study demonstrated the overall safety of TMS in the treatment of AGA.

Relationship between locked modes and thermal quenches in DIII-D

NASA Astrophysics Data System (ADS)

Sweeney, R.; Choi, W.; Austin, M.; Brookman, M.; Izzo, V.; Knolker, M.; La Haye, R. J.; Leonard, A.; Strait, E.; Volpe, F. A.; The DIII-D Team

2018-05-01

Locked modes are known to be one of the major causes of disruptions, but the physical mechanisms by which locking leads to disruptions are not well understood. Here we analyze the evolution of the temperature profile in the presence of multiple coexisting locked modes during partial and full thermal quenches. Partial quenches are often observed to be an initial, distinct stage in the full thermal quench. Near the onset of partial quenches, locked island O-points are observed to align with each other on the midplane, and their widths are sufficient to overlap each other, as indicated by the Chirikov parameter. Energy conservation analysis of one partial thermal quench shows that the energy lost is both radiated in the divertor region, and conducted or convected to the divertor. Nonlinear resistive magnetohydrodynamic simulations support the interpretation of stochastic fields causing a partial axisymmetric collapse, though the simulated temperature profile exhibits less degradation than the experimental profiles. In discharges with minimum values of the safety factor above  ∼1.2, locked modes are observed to self-stabilize by inducing, possibly via double tearing modes, a minor disruption that removes their neoclassical drive. These high q min discharges often exhibit relatively low ratios of the plasma internal inductance to the safety factor at 95% of the poloidal flux, which might imply classical stability, in agreement with the decay of the mode when the neoclassical drive is removed.

Considerations for management of patients with diabetic macular edema: Optimizing treatment outcomes and minimizing safety concerns through interdisciplinary collaboration.

PubMed

Strain, W David; Cos, Xavier; Prünte, Christian

2017-04-01

Diabetes is a growing worldwide epidemic and a leading cause of blindness in working-age people around the world. Diabetic retinopathy (DR) and diabetic macular edema (DME) are common causes of visual impairment in people with diabetes and often indicate the presence of diabetes-associated preclinical micro- and macrovascular complications. As such, patients with DR and DME often display complex, highly comorbid profiles. Several treatments are currently available for the treatment of DME, including anti-vascular endothelial growth factor (VEGF) agents, which are administered via intravitreal injection. While the safety profiles of approved ocular anti-VEGF therapies have been reassuring, the high-risk nature of the DME patient population means that treatment must be carefully considered and a holistic approach to disease management should be taken. This requires multidisciplinary, collaborative care involving all relevant specialties to ensure that patients not only receive prompt treatment for DME but also appropriate consideration is taken of any systemic comorbidities to evaluate and minimize potentially serious safety issues. Copyright © 2017. Published by Elsevier B.V.

[Safety profile of zolpidem: two studies of 3805 patients by Swiss practitioners].

PubMed

Ganzoni, E; Gugger, M

1999-06-24

Evaluation and treatment of insomnia are frequent procedures in the physician's everyday practice, since many patients seek medical treatment for this condition. Knowledge of pharmacological therapeutical alternatives is therefore decisive, in order to identify the most efficaceous and safe therapy for the patient among the available hypnotics. The short-acting hypnotic zolpidem has been investigated in Switzerland in two multicenter safety studies in ambulatory practice. In the first study 8.9% (n = 125 of 1,972 treated patients), and in the second 7.2% of the patients (n = 175 of 1,833 treated patients) reported an adverse event. The most frequent events were related to the central nervous system (CNS) (somnolence, headache, confusion, vertigo); gastrointestinal and cutaneous symptoms were the most frequent non CNS-dependent effects. New, unknown or serious adverse events were not found and no specific risk factor or population at risk was identified. The safety profile of zolpidem is consistent with its known pharmacological properties, the results of previous clinical trials and the international experience obtained in large patients groups.

Evolution of the central safety factor during stabilized sawtooth instabilities at KSTAR

NASA Astrophysics Data System (ADS)

Messmer, M. C. C.; Ko, J.; Chung, J.; Woo, M. H.; Lee, K.-D.; Jaspers, R. J. E.

2018-01-01

A motional Stark effect (MSE) diagnostic has recently been installed in the KSTAR tokamak. A difficulty faced at KSTAR and common to other MSE diagnostics is calibration of the system for absolute measurements. In this report we present our novel calibration routine and discuss first results, evaluating the evolution of the the central safety factor during sawtooth instabilities. The calibration scheme ensures that the bandpass filters typically used in MSE systems are aligned correctly and identifies and removes systematic offsets present in the measurement. This is verified by comparing the reconstructed safety factor profile against various discharges where the locations of rational q surfaces have been obtained from MHD markers. The calibration is applied to analyse the evolution of q 0 in a shot where the sawteeth are stabilized by neutral beam injection. Within the analysed sawtooth periods q 0 drops below unity during the quiescent phase and relaxes close to or slightly above unity at the sawtooth crash. This finding is in line with the classical Kadomtsev model of full magnetic reconnection and earlier findings at JET.

Opportunities for improved diabetes care among patients of safety net practices: a safety net providers' strategic alliance study.

PubMed

Reichsman, Ann; Werner, James; Cella, Peggi; Bobiak, Sarah; Stange, Kurt C

2009-01-01

To identify barriers and opportunities for quality diabetes care in safety net practices. In 3 federally qualified health centers and 1 free clinic, 19 primary care clinicians profiled patient and visit characteristics and quality of care measures for 181 consecutive visits by adult type 2 diabetic patients. Open-ended questions assessed patient and clinician perception of barriers to diabetes care and patient report of enabling factors. A multidisciplinary team identified themes from open-ended responses. Logistic regression analyses assessed the association of the identified barriers/enablers with 2 measures of quality care: glycosylated hemoglobin and prophylactic aspirin use. Ranked barriers noted by patients included adherence (40%), financial/insurance (23%), and psychosocial (13%) factors. Clinicians ranked systemic factors, including financial/ insurance (32%) and cultural/psychosocial (29%) factors, as important to adherence (29%) in determining quality diabetes care. Patients reported dietary and medical adherence (37%) and family/health care worker support (17%) as helpful factors. Among 175 patients with available data, glycosylated hemoglobin levels were associated with patient report of financial/insurance factors both as a barrier when visits and medications were unaffordable and as an opportunity when free or low-cost medications and services were provided. Patients' adherence with aspirin prophylaxis was strongly associated with African American race, prior prescription of aspirin and distribution of aspirin at the practice site (p<.001). Patients were less likely than clinicians to identify systemic and contextual factors contributing to poor diabetes care. From the front line's perspective, enabling patient self-management and systemic support is a target for improving diabetes care in safety net practices.

Efficacy and safety of a clinically relevant foamy vector design in human hematopoietic repopulating cells.

PubMed

Everson, Elizabeth M; Hocum, Jonah D; Trobridge, Grant D

2018-06-23

Previous studies have shown that foamy viral (FV) vectors are a promising alternative to gammaretroviral and lentiviral vectors and insulators can improve FV vector safety. However, in a previous analysis of insulator effects on FV vector safety, strong viral promoters were used to elicit genotoxic events. Here we developed and analyzed the efficacy and safety of a high-titer, clinically relevant FV vector driven by the housekeeping promoter elongation factor-1α and insulated with an enhancer blocking A1 insulator (FV-EGW-A1). Human CD34 + cord blood cells were exposed to an enhanced green fluorescent protein expressing vector, FV-EGW-A1, at a multiplicity of infection of 10 and then maintained in vitro or transplanted into immunodeficient mice. Flow cytometry was used to measure engraftment and marking in vivo. FV vector integration sites were analyzed to assess safety. FV-EGW-A1 resulted in high-marking, multi-lineage engraftment of human repopulating cells with no evidence of silencing. Engraftment was highly polyclonal with no clonal dominance and a promising safety profile based on integration site analysis. An FV vector with an elongation factor-1α promoter and an A1 insulator is a promising vector design for use in the clinic. This article is protected by copyright. All rights reserved.

Emerging therapies for hemophilia: controversies and unanswered questions

PubMed Central

Arruda, Valder R.; Doshi, Bhavya S.; Samelson-Jones, Benjamin J.

2018-01-01

Several new therapies for hemophilia have emerged in recent years. These strategies range from extended half-life factor replacement products and non-factor options with improved pharmacokinetic profiles to gene therapy aiming for phenotypic cure. While these products have the potential to change hemophilia care dramatically, several challenges and questions remain regarding broader applicability, long-term safety, and which option to pursue for each patient. Here, we review these emerging therapies with a focus on controversies and unanswered questions in each category. PMID:29770199

Safety and Effectiveness of Highly Active Antiretroviral Therapy in Treatment-Naïve HIV Patients: Preliminary Findings of a Cohort Event Monitoring Study in Belarus.

PubMed

Setkina, Svetlana; Dotsenko, Marina; Bondar, Sviatlana; Charnysh, Iryna; Kuchko, Alla; Kaznacheeva, Alena; Kozorez, Elena; Dodaleva, Alena; Rossa, Natalia

2015-04-01

Antiretroviral drugs have well-documented evidence-based favorable benefit-risk ratios. Although various studies have investigated and characterized the safety profile of antiretroviral medicines, there are a limited number of studies evaluating the safety of first-line antiretroviral therapy (ART) in patients with a specific co-morbidity. A cohort event monitoring (CEM) study of the safety and effectiveness of antiretroviral medicines in a target population that has a significant level of co-morbidities (chronic infectious diseases, peripheral blood cytopenias) was implemented. The aim was to evaluate the safety profile of the highly active ART (HAART) in the target population and subpopulations with risk factors, to optimize the monitoring and decision-making procedure for subgroups of patients with specific types of co-morbidity, and to implement a more vigilant approach to therapy management in risk groups of patients. Prospective observational CEM was implemented among HAART-naïve HIV-positive patients at four clinical sites from December 2012. Eligible patients were those starting first-line HAART. Close medical supervision of all enrolled patients, with regular clinical and laboratory monitoring, was provided by healthcare professionals within 1 year after commencement of therapy. Standardized forms were used for data collection on initial and subsequent visits. All objective or subjective deviations in condition (events) were assessed for a causal relationship with ART, and for severity, seriousness, reversibility, preventability, and pre-existing risk factors in the case of adverse drug reactions (ADRs). A total of 518 HAART-naïve HIV-positive patients were enrolled in the CEM study. Of these patients, 65% (337) experienced one or several ADRs related to one or more components of HAART. Most of the ADRs reported were non-serious, expected, common (very common), transient (correctable), or reversible. The most common were hematotoxic, hepatotoxic, and neurotoxic adverse reactions. In several cases, some types of toxicities, associated with zidovudine, efavirenz, and nevirapine, had a high level of severity, necessitating hospitalization and drug regimen or single-agent substitution. Severe cases of hematological, hepatobiliary, and psychiatric toxicities were associated with pre-existing risk factors. CEM is an effective tool for safety and effectiveness monitoring and could be successfully implemented for intensive study of important safety issues and for overcoming knowledge gaps regarding safety. In order to achieve a favorable benefit-risk ratio for HAART in the specific sections of the population with pre-existing risk factors for development of ART toxicities, more vigilant consideration and careful assessment before therapy is commenced and further regular monitoring of key laboratory parameters is required.

Inroads into Equestrian Safety: Rider-Reported Factors Contributing to Horse-Related Accidents and Near Misses on Australian Roads.

PubMed

Thompson, Kirrilly; Matthews, Chelsea

2015-07-22

Horse riding and horse-related interactions are inherently dangerous. When they occur on public roads, the risk profile of equestrian activities is complicated by interactions with other road users. Research has identified speed, proximity, visibility, conspicuity and mutual misunderstanding as factors contributing to accidents and near misses. However, little is known about their significance or incidence in Australia. To explore road safety issues amongst Australian equestrians, we conducted an online survey. More than half of all riders (52%) reported having experienced at least one accident or near miss in the 12 months prior to the survey. Whilst our findings confirm the factors identified overseas, we also identified issues around rider misunderstanding of road rules and driver misunderstanding of rider hand signals. Of particular concern, we also found reports of potentially dangerous rider-directed road rage. We identify several areas for potential safety intervention including (1) identifying equestrians as vulnerable road users and horses as sentient decision-making vehicles (2) harmonising laws regarding passing horses, (3) mandating personal protective equipment, (4) improving road signage, (5) comprehensive data collection, (6) developing mutual understanding amongst road-users, (7) safer road design and alternative riding spaces; and (8) increasing investment in horse-related safety initiatives.

Cardiovascular safety of biologic therapies for the treatment of RA.

PubMed

Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

2011-11-15

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Psychosocial influences on safety climate: evidence from community pharmacies.

PubMed

Phipps, Denham L; Ashcroft, Darren M

2011-12-01

To examine the relationship between psychosocial job characteristics and safety climate. Cross-sectional survey. Community pharmacies in Great Britain. Participants A random sample of community pharmacists registered in Great Britain (n = 860). Survey instruments Effort-reward imbalance (ERI) indicator and Job Content Questionnaire (JCQ). Main outcome measures Pharmacy Safety Climate Questionnaire (PSCQ). The profile of scores from the ERI indicated a relatively high risk of adverse psychological effects. The profile of scores from the JCQ indicated both high demand on pharmacists and a high level of psychological and social resources to meet these demands. Path analysis confirmed a model in which the ERI and JCQ measures, as well as the type of pharmacy and pharmacist role, predicted responses to the PSCQ (χ(2)(36) = 111.38, p < 0.001; Tucker-Lewis index = 0.96; comparative fit index = 0.98; root mean square error of approximation=0.05). Two general factors (effort vs reward and control vs demand) accounted for the effect of job characteristics on safety climate ratings; each had differential effects on the PSCQ scales. The safety climate in community pharmacies is influenced by perceptions of job characteristics, such as the level of job demands and the resources available to meet these demands. Hence, any efforts to improve safety should take into consideration the effect of the psychosocial work environment on safety climate. In addition, there is a need to address the presence of work-related stressors, which have the potential to cause direct or indirect harm to staff and service users. The findings of the current study provide a basis for future research to improve the safety climate and well-being, both in the pharmacy profession and in other healthcare settings.

Analysis of Workplace Accidents in Automotive Repair Workshops in Spain.

PubMed

López-Arquillos, Antonio; Rubio-Romero, Juan Carlos

2016-09-01

To analyze the effects of the factors associated with different types of injury (superficial wounds, dislocations and sprains, bone fractures, concussion and internal injuries, burns scalding and freezing) caused by occupational accidents in automotive repair workshops. Study of a sample consisting of 89,954 industry accidents reported from 2003 to 2008. Odds ratios were calculated with a 95% confidence interval. Belonging to a small company is a risk factor for suffering three of the five types of injury studied. Women are less likely to suffer burns and superficial wounds, and more likely to suffer dislocations or sprains. Foreign workers are more likely to suffer concussion and internal injuries. Health and safety strategies and accident prevention measures should be individualized and adapted to the type of worker most likely to be injured in each type of accident. Occupational health and safety training courses designed according to worker profile, and improving the participation of the workers in small firms creating regional or roving safety representatives would improve working conditions.

Magnetic flux pumping mechanism prevents sawtoothing in 3D nonlinear MHD simulations of tokamak plasmas

NASA Astrophysics Data System (ADS)

Krebs, Isabel; Jardin, Stephen C.; Guenter, Sibylle; Lackner, Karl; Hoelzl, Matthias; Strumberger, Erika; Ferraro, Nate

2017-10-01

3D nonlinear MHD simulations of tokamak plasmas have been performed in toroidal geometry by means of the high-order finite element code M3D-C1. The simulations are set up such that the safety factor on axis (q0) is driven towards values below unity. As reported in and the resulting asymptotic states either exhibit sawtooth-like reconnection cycling or they are sawtooth-free. In the latter cases, a self-regulating magnetic flux pumping mechanism, mainly provided by a saturated quasi-interchange instability via a dynamo effect, redistributes the central current density so that the central safety factor profile is flat and q0 1 . Sawtoothing is prevented if β is sufficiently high to allow for the necessary amount of flux pumping to counterbalance the tendency of the current density profile to centrally peak. We present the results of 3D nonlinear simulations based on specific types of experimental discharges and analyze their asymptotic behavior. A set of cases is presented where aspects of the current ramp-up phase of Hybrid ASDEX Upgrade discharges are mimicked. Another set of simulations is based on low-qedge discharges in DIII-D.

Simulation of the alpha particle heating and the helium ash source in an International Thermonuclear Experimental Reactor-like tokamak with an internal transport barrier

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

Ye, Lei, E-mail: lye@ipp.ac.cn; Guo, Wenfeng; Xiao, Xiaotao

2014-12-15

A guiding center orbit following code, which incorporates a set of non-singular coordinates for orbit integration, was developed and applied to investigate the alpha particle heating in an ITER-like tokamak with an internal transport barrier. It is found that a relatively large q (safety factor) value can significantly broaden the alpha heating profile in comparison with the local heating approximation; this broadening is due to the finite orbit width effects; when the orbit width is much smaller than the scale length of the alpha particle source profile, the heating profile agrees with the source profile, otherwise, the heating profile canmore » be significantly broadened. It is also found that the stagnation particles move to the magnetic axis during the slowing-down process, thus the effect of stagnation orbits is not beneficial to the helium ash removal. The source profile of helium ash is broadened in comparison with the alpha source profile, which is similar to the heating profile.« less

Efficacy and safety profile of xanthines in COPD: a network meta-analysis.

PubMed

Cazzola, Mario; Calzetta, Luigino; Barnes, Peter J; Criner, Gerard J; Martinez, Fernando J; Papi, Alberto; Gabriella Matera, Maria

2018-06-30

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD. Copyright ©ERS 2018.

Drug formulary review process for sargramostim and filgrastim: focus on analysis of adverse drug reactions.

PubMed

Kellihan, M J

1993-01-01

Selection of a drug for formulary inclusion involves evaluation of safety, efficacy, and cost. The colony-stimulating factors (CSFs) sargramostim and filgrastim have a broad range of potential indications and represent a costly formulary addition when acquisition price alone is considered; their comparative safety is unclear. These factors suggest that the CSFs should be closely scrutinized prior to formulary addition. In the absence of direct comparative studies, an assessment of the safety of CSFs involves evaluation of information provided in the product circular, official drug compendia, adverse biologic reports submitted to the United States Food and Drug Administration, and data from key clinical trials. Data in the product circulars report on adverse events in small numbers of patients treated for chemotherapy-induced neutropenia (filgrastim) or neutropenia subsequent to bone marrow transplantation (sargramostim). The official compendia and clinical trials include experience with CSFs produced in a variety of expression systems; these data are not limited to sargramostim and filgrastim. Importantly, there was a similar incidence of adverse events in patients who received sargramostim or filgrastim and in those who took placebo reported in the product circulars and the pivotal trials, suggesting that the underlying disease may have an important role in determining the side-effect profile of these agents. Adverse biologic reports represent experience with sargramostim and filgrastim obtained under actual clinical conditions and suggest that the same types of adverse events are seen with sargramostim as with filgrastim. This analysis suggests that a decision to select filgrastim over sargramostim for formulary inclusion based on the safety profile is not appropriate because currently available data are equivocal and that such decisions would more appropriately be based on efficacy and cost.

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

PubMed Central

2017-01-01

Introduction Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. Methods A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. Results The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Conclusion Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors. PMID:29077727

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

PubMed

Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

2017-01-01

Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk factors.

Risk-based Strategy to Determine Testing Requirement for the Removal of Residual Process Reagents as Process-related Impurities in Bioprocesses.

PubMed

Qiu, Jinshu; Li, Kim; Miller, Karen; Raghani, Anil

2015-01-01

The purpose of this article is to recommend a risk-based strategy for determining clearance testing requirements of the process reagents used in manufacturing biopharmaceutical products. The strategy takes account of four risk factors. Firstly, the process reagents are classified into two categories according to their safety profile and history of use: generally recognized as safe (GRAS) and potential safety concern (PSC) reagents. The clearance testing of GRAS reagents can be eliminated because of their safe use historically and process capability to remove these reagents. An estimated safety margin (Se) value, a ratio of the exposure limit to the estimated maximum reagent amount, is then used to evaluate the necessity for testing the PSC reagents at an early development stage. The Se value is calculated from two risk factors, the starting PSC reagent amount per maximum product dose (Me), and the exposure limit (Le). A worst-case scenario is assumed to estimate the Me value, that is common. The PSC reagent of interest is co-purified with the product and no clearance occurs throughout the entire purification process. No clearance testing is required for this PSC reagent if its Se value is ≥1; otherwise clearance testing is needed. Finally, the point of the process reagent introduction to the process is also considered in determining the necessity of the clearance testing for process reagents. How to use the measured safety margin as a criterion for determining PSC reagent testing at process characterization, process validation, and commercial production stages are also described. A large number of process reagents are used in the biopharmaceutical manufacturing to control the process performance. Clearance testing for all of the process reagents will be an enormous analytical task. In this article, a risk-based strategy is described to eliminate unnecessary clearance testing for majority of the process reagents using four risk factors. The risk factors included in the strategy are (i) safety profile of the reagents, (ii) the starting amount of the process reagents used in the manufacturing process, (iii) the maximum dose of the product, and (iv) the point of introduction of the process reagents in the process. The implementation of the risk-based strategy can eliminate clearance testing for approximately 90% of the process reagents used in the manufacturing processes. This science-based strategy allows us to ensure patient safety and meet regulatory agency expectations throughout the product development life cycle. © PDA, Inc. 2015.

Steady state scenario development with elevated minimum safety factor on DIII-D

DOE PAGES

Holcomb, Christopher T.; Ferron, John R.; Luce, Timothy C.; ...

2014-08-15

On DIII-D, a high β scenario with minimum safety factor (q min) near 1.4 has been optimized with new tools and shown to be a favourable candidate for long pulse or steady state operation in future devices. Furthermore, the new capability to redirect up to 5 MW of neutral beam injection (NBI) from on- to off-axis improves the ability to sustain elevated q min with a less peaked pressure profile. The observed changes increase the ideal magnetohydrodynamics (MHD) n = 1 mode β N limit thus providing a path forward for increasing the noninductive current drive fraction by operating atmore » high β N. Quasi-stationary discharges free of tearing modes have been sustained at βN = 3.5 and β T = 3.6% for two current profile diffusion timescales (about 3 s) limited by neutral beam duration. The discharge performance has normalized fusion performance expected to give fusion gain Q ≈ 5 in a device the size of ITER. Analysis of the poloidal flux evolution and current drive balance show that the loop voltage profile is almost relaxed even with 25% of the current driven inductively, and q min remains elevated near 1.4. Our observations increase confidence that the current profile will not evolve to one unstable to a tearing mode. In preliminary tests a divertor heat flux reduction technique based on producing a radiating mantle with neon injection appears compatible with this operating scenario. 0D model extrapolations suggest it may be possible to push this scenario up to 100% noninductive current drive by raising β N. Similar discharges with q min = 1.5–2 were susceptible to tearing modes and off-axis fishbones, and with q min > 2 lower normalized global energy confinement time is observed.« less

Relationship between locked modes and thermal quenches in DIII-D

DOE PAGES

Sweeney, R.; Choi, W.; Austin, M.; ...

2018-03-28

Locked modes are known to be one of the major causes of disruptions, but the physical mechanisms by which locking leads to disruptions are not well understood. For this study, we analyze the evolution of the temperature profile in the presence of multiple coexisting locked modes during partial and full thermal quenches. Partial quenches are often observed to be an initial, distinct stage in the full thermal quench. Near the onset of partial quenches, locked island O-points are observed to align with each other on the midplane, and their widths are sufficient to overlap each other, as indicated by themore » Chirikov parameter. Energy conservation analysis of one partial thermal quench shows that the energy lost is both radiated in the divertor region, and conducted or convected to the divertor. Nonlinear resistive magnetohydrodynamic simulations support the interpretation of stochastic fields causing a partial axisymmetric collapse, though the simulated temperature profile exhibits less degradation than the experimental profiles. In discharges with minimum values of the safety factor above ~1.2, locked modes are observed to self-stabilize by inducing, possibly via double tearing modes, a minor disruption that removes their neoclassical drive. These high q min discharges often exhibit relatively low ratios of the plasma internal inductance to the safety factor at 95% of the poloidal flux, which might imply classical stability, in agreement with the decay of the mode when the neoclassical drive is removed.« less

Feasibility of a far infrared laser based polarimeter diagnostic system for the JT-60SA fusion experiment

NASA Astrophysics Data System (ADS)

Boboc, A.; Gil, C.; Terranova, D.; Orsitto, F. P.; Soare, S.; Lotte, P.; Sozzi, C.; Imazawa, R.; Kubo, H.

2018-07-01

JT-60SA is the large Tokamak device that is being built in Japan under the Broader Approach Satellite Tokamak Programme and the Japanese National Programme and will operate as a satellite machine for ITER. The main goal of the JT-60SA Programme is to provide valuable information for the ITER steady-state scenario and for the design of DEMO, where the real-time control of the safety factor profile is very important, in connection with both MHD stability and plasma confinement. It has been demonstrated in this work that to this end polarimetry measurements are necessary, in particular in order to reconstruct the safety factor profile in reversed shear scenarios. In this paper we present the main steps of a conceptual feasibility study of a multi-channel polarimeter diagnostic and the resulting optimised geometry. In this study, magnetic scenario modelling, a realistic CAD-driven design and long-term operation requirements, rarely even considered at this stage, have been considered. It is shown that a far infrared polarimeter system, with a laser operating at a wavelength of 194.7 μm and up to twelve channels can be envisaged for JT-60SA. The top requirements can be attained, i.e., that the polarimeter, together with other diagnostic measurements, should provide q-profile reconstruction with an accuracy of 10% for the entire plasma cycle and suitable time resolution for real-time applications, in particular in high density and ITER-relevant plasma scenarios.

Relationship between locked modes and thermal quenches in DIII-D

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

Sweeney, R.; Choi, W.; Austin, M.

Locked modes are known to be one of the major causes of disruptions, but the physical mechanisms by which locking leads to disruptions are not well understood. For this study, we analyze the evolution of the temperature profile in the presence of multiple coexisting locked modes during partial and full thermal quenches. Partial quenches are often observed to be an initial, distinct stage in the full thermal quench. Near the onset of partial quenches, locked island O-points are observed to align with each other on the midplane, and their widths are sufficient to overlap each other, as indicated by themore » Chirikov parameter. Energy conservation analysis of one partial thermal quench shows that the energy lost is both radiated in the divertor region, and conducted or convected to the divertor. Nonlinear resistive magnetohydrodynamic simulations support the interpretation of stochastic fields causing a partial axisymmetric collapse, though the simulated temperature profile exhibits less degradation than the experimental profiles. In discharges with minimum values of the safety factor above ~1.2, locked modes are observed to self-stabilize by inducing, possibly via double tearing modes, a minor disruption that removes their neoclassical drive. These high q min discharges often exhibit relatively low ratios of the plasma internal inductance to the safety factor at 95% of the poloidal flux, which might imply classical stability, in agreement with the decay of the mode when the neoclassical drive is removed.« less

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

PubMed

Gavin, Paul D; Simon, Lee S; Schlagheck, Thomas; Smith, Alisha J; Shakib, Sepehr

2017-07-01

To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM). Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h. Oxycodone was detected 8.0 ± 2.7-h postpatch administration, reaching a mean maximum plasma concentration of 3.41 ± 1.34 ng/ml at 49.3 ± 21.2 h. The safety profile was consistent with the application method and known side-effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation was observed. A 3-day application of the TPM/oxycodone patch demonstrated an acceptable safety profile and was well tolerated by healthy subjects, with limited dermal irritation following application.

The Kaiser Permanente implant registries: effect on patient safety, quality improvement, cost effectiveness, and research opportunities.

PubMed

Paxton, Elizabeth W; Inacio, Maria Cs; Kiley, Mary-Lou

2012-01-01

Considering the high cost, volume, and patient safety issues associated with medical devices, monitoring of medical device performance is critical to ensure patient safety and quality of care. The purpose of this article is to describe the Kaiser Permanente (KP) implant registries and to highlight the benefits of these implant registries on patient safety, quality, cost effectiveness, and research. Eight KP implant registries leverage the integrated health care system's administrative databases and electronic health records system. Registry data collected undergo quality control and validation as well as statistical analysis. Patient safety has been enhanced through identification of affected patients during major recalls, identification of risk factors associated with outcomes of interest, development of risk calculators, and surveillance programs for infections and adverse events. Effective quality improvement activities included medical center- and surgeon-specific profiles for use in benchmarking reports, and changes in practice related to registry information output. Among the cost-effectiveness strategies employed were collaborations with sourcing and contracting groups, and assistance in adherence to formulary device guidelines. Research studies using registry data included postoperative complications, resource utilization, infection risk factors, thromboembolic prophylaxis, effects of surgical delay on concurrent injuries, and sports injury patterns. The unique KP implant registries provide important information and affect several areas of our organization, including patient safety, quality improvement, cost-effectiveness, and research.

Central Safety Factor and Normalized Beta Control Under Near-Zero Input Torque Constraints in DIII-D

NASA Astrophysics Data System (ADS)

Pajares, Andres; Wehner, William; Schuster, Eugenio; Burrell, Keith; Ferron, John; Walker, Michael; Humphreys, David; Lehigh University Team; Atomics Team, General

2017-10-01

DIII-D experiments have assessed the capability of combined central safety factor (q0) and normalized beta (βN) control under near-zero net torque to facilitate access to QH-mode with reverse Ip and normal Bt. Regulation of q0 and βN can prevent magneto-hydrodynamic instabilities that deteriorate plasma performance in discharges with a monotonically increasing safety-factor profile. Zero-input-torque scenarios are of special interest because future burning plasma tokamaks such as ITER will most likely operate with very low input torque, which makes these scenarios more susceptible to locked modes. To support studies of such scenarios, a controller for simultaneous regulation of q0 and βN has been developed using near-zero net input torque actuators including balanced neutral beam injection (NBI) and electron-cyclotron heating & current drive (ECH/ECCD). Experimental results show that in spite of the presence of locked modes the use of feedback control resulted in good tracking of the commanded q0 and βN when both ECCD/ECH and NBI were available. Supported by the US DOE under DE-SC0010661 and DE-FC02-04ER54698.

An update on the safety of nutraceuticals and effects on lipid parameters.

PubMed

Cicero, Arrigo F G; Colletti, Alessandro

2018-03-01

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability in developed countries, whereas a large portion of patients in primary prevention have uncontrolled level of CVD risk factors. Dietary supplementation with bioactive natural compounds with demonstrated lipid-lowering effects is currently supported by the international guidelines for CVD prevention and some international expert panels. Areas covered: This review provides insights on issues concerning the tolerability and safety of the most commonly used nutraceuticals with demonstrated lipid-lowering effect in humans. They will be then divided into three main categories according to their mechanism of action (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors, and LDL-C excretion stimulants) and their pharmacological profile will be discussed. Expert opinion: A growing body of preclinical, epidemiological and clinical evidence has defined the tolerability and safety profile of the most commonly used lipid-lowering nutraceuticals. In the most part of cases, the side effects are mild and reversible. However, detailed knowledge of specific health risks and pharmacological interactions for each individual compound is needed for the management of frail patients, such as children, elderly, patients with liver or renal failure, and patients consuming numerous drugs.

From ontology selection and semantic web to an integrated information system for food-borne diseases and food safety.

PubMed

Yan, Xianghe; Peng, Yun; Meng, Jianghong; Ruzante, Juliana; Fratamico, Pina M; Huang, Lihan; Juneja, Vijay; Needleman, David S

2011-01-01

Several factors have hindered effective use of information and resources related to food safety due to inconsistency among semantically heterogeneous data resources, lack of knowledge on profiling of food-borne pathogens, and knowledge gaps among research communities, government risk assessors/managers, and end-users of the information. This paper discusses technical aspects in the establishment of a comprehensive food safety information system consisting of the following steps: (a) computational collection and compiling publicly available information, including published pathogen genomic, proteomic, and metabolomic data; (b) development of ontology libraries on food-borne pathogens and design automatic algorithms with formal inference and fuzzy and probabilistic reasoning to address the consistency and accuracy of distributed information resources (e.g., PulseNet, FoodNet, OutbreakNet, PubMed, NCBI, EMBL, and other online genetic databases and information); (c) integration of collected pathogen profiling data, Foodrisk.org ( http://www.foodrisk.org ), PMP, Combase, and other relevant information into a user-friendly, searchable, "homogeneous" information system available to scientists in academia, the food industry, and government agencies; and (d) development of a computational model in semantic web for greater adaptability and robustness.

Evaluation of liquefaction potential for building code

NASA Astrophysics Data System (ADS)

Nunziata, C.; De Nisco, G.; Panza, G. F.

2008-07-01

The standard approach for the evaluation of the liquefaction susceptibility is based on the estimation of a safety factor between the cyclic shear resistance to liquefaction and the earthquake induced shear stress. Recently, an updated procedure based on shear-wave velocities (Vs) has been proposed which could be more easily applied. These methods have been applied at La Plaja beach of Catania, that experienced liquefaction because of the 1693 earthquake. The detailed geotechnical and Vs information and the realistic ground motion computed for the 1693 event let us compare the two approaches. The successful application of the Vs procedure, slightly modified to fit historical and safety factor information, even if additional field performances are needed, encourages the development of a guide for liquefaction potential analysis, based on well defined Vs profiles to be included in the italian seismic code.

Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

PubMed Central

2013-01-01

Background This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. Methods We included 71 critical incidents in primary midwifery care and subsequent hospital care in case of referral after 36 weeks of pregnancy that were related to substandard care and for that reason were reported to the Health Care Inspectorate in The Netherlands in 36 months (n = 357). We performed a case-by-case analysis, using a previously validated instrument which covered five broad domains: healthcare organization, communication between healthcare providers, patient risk factors, clinical management, and clinical outcomes. Results Determinants that were associated with risk concerned healthcare organization (n = 20 incidents), communication about treatment procedures (n = 39), referral processes (n = 19), risk assessment by telephone triage (n = 10), and clinical management in an out of hours setting (n = 19). The 71 critical incidents included three cases of maternal death, eight cases of severe maternal morbidity, 42 perinatal deaths and 12 critical incidents with severe morbidity for the child. Suboptimal prenatal risk assessment, a delay in availability of health care providers in urgent situations, miscommunication about treatment between care providers, and miscommunication with patients in situations with a language barrier were associated with safety risks. Conclusions Systematic analysis of critical incidents improves insight in determinants of safety risk. The wide variety of determinants of risk of critical incidents implies that there is no single intervention to improve patient safety in the care for pregnant women with initially a low risk profile. PMID:24286376

Psychophysiology and posttraumatic stress disorder symptom profile in pregnant African-American women with trauma exposure.

PubMed

Michopoulos, Vasiliki; Rothbaum, Alex O; Corwin, Elizabeth; Bradley, Bekh; Ressler, Kerry J; Jovanovic, Tanja

2015-08-01

While female sex is a robust risk factor for posttraumatic stress disorder (PTSD), pregnant women are an understudied population in regards to PTSD symptom expression profiles. Because circulating hormones during pregnancy affect emotionality, we assessed whether pregnant women would have increased expression of the intermediate phenotypes of hyperarousal and fear-potentiated startle (FPS) compared to non-pregnant women. We examined PTSD symptom profiles in pregnant (n = 207) and non-pregnant women (n = 370). In a second study, FPS responses were assessed in 15 pregnant and 24 non-pregnant women. All participants were recruited from the obstetrics and gynecology clinic at a public hospital serving a primarily African-American, low socioeconomic status, inner-city population. Our results indicate that overall PTSD symptoms were not different between the groups of women. However, pregnant women reported being more hypervigilant (p = 0.036) than non-pregnant women. In addition, pregnant women showed increased FPS to a safety signal compared to non-pregnant women (p = 0.024). FPS to a safety signal in pregnant women was significantly correlated with PTSD hyperarousal symptoms (r = 0.731, p < 0.001). Furthermore, discrimination between danger and safety signals was present in non-pregnant women (p = 0.008), but not in pregnant women (p = 0.895). Together, these data suggest that pregnant women show clinical and psychophysiological hyperarousal compared to non-pregnant women, and support screening for PTSD and assessment of PTSD risk in pregnant women.

Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

PubMed

Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

2013-11-01

Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data.

PubMed

Endrikat, J; Schwenke, C; Prince, M R

2015-07-01

To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18-64 years. Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. Copyright © 2015 The Royal College of Radiologists. All rights reserved.

Second Annual Clinical Diabetes Technology Meeting

DTIC Science & Technology

2006-05-01

glucose levels in Type 2 diabetes. He emphasized the excellent safety profile of this drug and its potential to promote weight loss in obese patients...monitoring of blood glucose (SMBG) is intended to: 1) educate patients about diet and exercise effects on glycemia; 2) protect patients by allowing...glucocentric. To reduce the risk of cardiovascular disease the comorbid risk factors, obesity , hypertension, dyslipidemia and the prothrombotic state need to be

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

Passive MHD Spectroscopy for Enabling Magnetic Reconstructions on Spherical Tokamak Plasmas at General Fusion Inc

NASA Astrophysics Data System (ADS)

O'Shea, Peter; Laberge, Michel; Mossman, Alex; Reynolds, Meritt

2017-10-01

Magnetic reconstructions on lab based plasma injectors at General Fusion relies heavily on edge magnetic (``Bdot'') probes. On plasma experiments built for field compression (PCS) tests, the number and locations of Bdot probes is limited by mechanical constraints. Additional information about the q profiles near the core in our Spector plasmas is obtained using passive MHD spectroscopy. The coaxial helicity injection (CHI) formation process naturally generates hollow current profiles and reversed shear early in each discharge. Central Ohmic heating naturally peaks the current profiles as our plasmas evolve in time, simultaneously reducing the core safety factor, q(0), and reverse shear. As the central, non-monotonic q-profile crosses rational flux surfaces, we observe transient magnetic reconnection events (MRE's) due to the double tearing mode. Modal analysis allows us to infer the q surfaces involved in each burst. The parametric dependence of the timing of MRE's allows us to estimate the continuous time evolution of the core q profile. Combining core MHD spectroscopy with edge magnetic probe measurements greatly enhances our certainty of the overall q profile.

[Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014].

PubMed

Prisco, Vincenzo; Iannaccone, Teresa; Tusciano, Adriano; Boccardi, Mariangela; Perris, Francesco; Capuano, Annalisa; Catapano, Francesco; Fabrazzo, Michele

2016-01-01

Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and comorbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in adverse drug reactions (ADRs). This study performes an analysis of Italian Medicine Agency data, in the section "signal analysis", to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (antiepileptics), N05 (antipsychotics), N06 (psycho-analectic drugs). Then we analysed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal. In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to antipsychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical antispychotics. Other correlations (6 above all) were found among antiepileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription. The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs' signaling is a classical system to provide the required attention in relation to a potential risk. The clinician in charge must report this because he is the key figure in the drugs' safety process. In psychiatry, in which a long-term pharmachological therapy is frequent, clinicians are requested to find and signal ADRs to the competent authority.

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

Investigating the radial structure of axisymmetric fluctuations in the TCV tokamak with local and global gyrokinetic GENE simulations

NASA Astrophysics Data System (ADS)

Merlo, G.; Brunner, S.; Huang, Z.; Coda, S.; Görler, T.; Villard, L.; Bañón Navarro, A.; Dominski, J.; Fontana, M.; Jenko, F.; Porte, L.; Told, D.

2018-03-01

Axisymmetric (n = 0) density fluctuations measured in the TCV tokamak are observed to possess a frequency f 0 which is either varying (radially dispersive oscillations) or a constant over a large fraction of the plasma minor radius (radially global oscillations) as reported in a companion paper (Z Huang et al, this issue). Given that f 0 scales with the sound speed and given the poloidal structure of density fluctuations, these oscillations were interpreted as Geodesic Acoustic Modes, even though f 0 is in fact smaller than the local linear GAM frequency {f}{GAM}. In this work we employ the Eulerian gyrokinetic code GENE to simulate TCV relevant conditions and investigate the nature and properties of these oscillations, in particular their relation to the safety factor profile. Local and global simulations are carried out and a good qualitative agreement is observed between experiments and simulations. By varying also the plasma temperature and density profiles, we conclude that a variation of the edge safety factor alone is not sufficient to induce a transition from global to radially inhomogeneous oscillations, as was initially suggested by experimental results. This transition appears instead to be the combined result of variations in the different plasma profiles, collisionality and finite machine size effects. Simulations also show that radially global GAM-like oscillations can be observed in all fluxes and fluctuation fields, suggesting that they are the result of a complex nonlinear process involving also finite toroidal mode numbers and not just linear global GAM eigenmodes.

Evaluation of bioavailability, efficacy, and safety profile of doxorubicin-loaded solid lipid nanoparticles

NASA Astrophysics Data System (ADS)

Patro, Nagaraju M.; Devi, Kshama; Pai, Roopa S.; Suresh, Sarasija

2013-12-01

We investigated the bioavailability, efficacy, and toxicity of doxorubicin-loaded solid lipid nanoparticles (DOX-SLNs) prepared by a simple modified double-emulsification method. A 3-factor, 3-level Box-Behnken statistical design was adopted in the optimization of DOX-SLN formulation considering dependent factors particle size and entrapment efficiency. Optimized SLN formulation composed of lipid (2 %) consisting of soya lecithin and Precirol ATO 5 (1:3) with Pluronic F68 (0.3 %) resulted in 217.36 ± 3.31 nm particle size and 59.45 ± 1.75 % entrapment efficiency. DOX-SLN exhibited significant enhancement ( p < 0.05) in bioavailability as compared with free DOX in Sprague-Dawley (SD) rats. DOX-SLN exhibited higher peak plasma concentration (6.761 ± 0.08 vs. 2.412 ± 0.04 μg/ml), increased AUC (61.368 ± 3.54 vs. 5.812 ± 0.49 μg/ml h), decreased clearance (36 ± 0.01 vs. 619 ± 0.005 mL/h kg), and volume of distribution (733 ± 0.092 vs. 2,064 ± 0.061 mL/kg) when compared to free DOX. The collective results of cardiac and kidney enzyme assay, antioxidant enzyme levels, hematological parameters, effect on body weight and tumor volume, tumor necrosis factor-α level, histopathological examination, and survival analysis confirmed the improved efficacy and safety profile of DOX-SLN in 7,12-dimethyl benzanthracene-induced breast cancer in SD rats.

Inroads into Equestrian Safety: Rider-Reported Factors Contributing to Horse-Related Accidents and Near Misses on Australian Roads

PubMed Central

Thompson, Kirrilly; Matthews, Chelsea

2015-01-01

Simple Summary Riding horses on roads can be dangerous, but little is known about accidents and near misses. To explore road safety issues amongst Australian equestrians, we conducted an online survey. More than half of all riders (52%) reported having experienced at least one accident or near miss in the 12 months prior to the survey, mostly attributed to speed. Whilst our findings confirmed factors identified overseas, we also identified issues around road rules, hand signals and road rage. This paper suggests strategies for improving the safety of horses, riders and other road users. Abstract Horse riding and horse-related interactions are inherently dangerous. When they occur on public roads, the risk profile of equestrian activities is complicated by interactions with other road users. Research has identified speed, proximity, visibility, conspicuity and mutual misunderstanding as factors contributing to accidents and near misses. However, little is known about their significance or incidence in Australia. To explore road safety issues amongst Australian equestrians, we conducted an online survey. More than half of all riders (52%) reported having experienced at least one accident or near miss in the 12 months prior to the survey. Whilst our findings confirm the factors identified overseas, we also identified issues around rider misunderstanding of road rules and driver misunderstanding of rider hand signals. Of particular concern, we also found reports of potentially dangerous rider-directed road rage. We identify several areas for potential safety intervention including (1) identifying equestrians as vulnerable road users and horses as sentient decision-making vehicles; (2) harmonising laws regarding passing horses; (3) mandating personal protective equipment; (4) improving road signage; (5) comprehensive data collection; (6) developing mutual understanding amongst road-users; (7) safer road design and alternative riding spaces; and (8) increasing investment in horse-related safety initiatives. PMID:26479376

A qualitative assessment of factors influencing acceptance of a new rotavirus vaccine among health care providers and consumers.

PubMed

Patel, Manish M; Janssen, Alan P; Tardif, Richard R; Herring, Mark; Parashar, Umesh D

2007-10-18

In 2006, a new rotavirus vaccine (RotaTeq) was licensed in the US and recommended for routine immunization of all US infants. Because a previously licensed vaccine (Rotashield) was withdrawn from the US for safety concerns, identifying barriers to uptake of RotaTeq will help develop strategies to broaden vaccine coverage. We explored beliefs and attitudes of parents (n = 57) and providers (n = 10) towards rotavirus disease and vaccines through a qualitative assessment using focus groups and in-depth interviews. All physicians were familiar with safety concerns about rotavirus vaccines, but felt reassured by RotaTeq's safety profile. When asked about likelihood of using RotaTeq on a scale of one to seven (1 = "absolutely not;" 7 = "absolutely yes") the mean score was 5 (range = 3-6). Physicians expressed a high likelihood of adopting RotaTeq, particularly if recommended by their professional organizations and expressed specific interest in post-marketing safety data. Similarly, consumers found the RotaTeq safety profile to be favorable and would rely on their physician's recommendation for vaccination. However, when asked to rank likelihood of having their child vaccinated against rotavirus (1 = "definitely not get;" 7 = "definitely get"), 29% ranked 1 or 2, 36% 3 or 4, and 35% 5 to 7. Our qualitative assessment provides complementary data to recent quantitative surveys and suggests that physicians and parents are likely to adopt the newly licensed rotavirus vaccine. Increasing parental awareness of the rotavirus disease burden and providing physicians with timely post-marketing surveillance data will be integral to a successful vaccination program.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

PubMed

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada.

PubMed

Reid, Robert L; Fortier, Michel P; Smith, Lynne; Mirkin, Sebastian; Grubb, Gary S; Constantine, Ginger D

2010-12-01

The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg. Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events. Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively. Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting. Copyright © 2010 Elsevier Inc. All rights reserved.

Visualizing variations in organizational safety culture across an inter-hospital multifaceted workforce.

PubMed

Kobuse, Hiroe; Morishima, Toshitaka; Tanaka, Masayuki; Murakami, Genki; Hirose, Masahiro; Imanaka, Yuichi

2014-06-01

To develop a reliable and valid questionnaire that can distinguish features of organizational culture for patient safety across subgroups such as hospitals, professions, management/non-management positions and units/wards. We developed a Hospital Organizational Culture Questionnaire based on a conceptual framework incorporating items from a review of existing literature. The questionnaire was administered to hospital staff including doctors, nurses, allied health personnel, and administrative staff at six public hospitals in Japan. Reliability and validity were assessed through exploratory factor analysis, multitrait scaling analysis, Cronbach's alpha coefficient and multiple regression analysis using staff-perceived achievement of safety as the response variable. Discriminative power across subgroups was assessed with radar chart profiling. Of the 3304 hospital staff surveyed, 2924 (88.5%) responded. After exploratory factor analysis and multitrait analysis, the finalized questionnaire was composed of 24 items in the following eight dimensions: improvement orientation, passion for mission, professional growth, resource allocation prioritization, inter-sectional collaboration, responsibility and authority, teamwork, and information sharing. Construct validity and internal consistency of dimensions were confirmed with multitrait analysis and Cronbach's alpha coefficients, respectively. Multiple regression analysis showed that improvement orientation, passion for mission, resource allocation prioritization and information sharing were significantly associated with higher achievement in safety practices. Our questionnaire tool was able to distinguish features of safety culture among different subgroups. Our questionnaire demonstrated excellent validity and reliability, and revealed distinct cultural patterns among different subgroups. Quantitative assessment of organizational safety culture with this tool may further the understanding of associated characteristics of each subgroup and provide insight into organizational readiness for patient safety improvement. © 2014 John Wiley & Sons, Ltd.

Nonsteroidal antagonists of the mineralocorticoid receptor.

PubMed

Kolkhof, Peter; Nowack, Christina; Eitner, Frank

2015-09-01

The broad clinical use of steroidal mineralocorticoid receptor antagonists (MRAs) is limited by the potential risk of inducing hyperkalemia when given on top of renin-angiotensin system blockade. Drug discovery campaigns have been launched aiming for the identification of nonsteroidal MRAs with an improved safety profile. This review analyses the evidence for the potential of improved safety profiles of nonsteroidal MRAs and the current landscape of clinical trials with nonsteroidal MRAs. At least three novel nonsteroidal MRAs have reportedly demonstrated an improved therapeutic index (i.e. less risk for hyperkalemia) in comparison to steroidal antagonists in preclinical models. Five pharmaceutical companies have nonsteroidal MRAs in clinical development with a clear focus on the treatment of chronic kidney diseases. No clinical data have been published so far for MT-3995 (Mitsubishi), SC-3150 (Daiichi-Sankyo), LY2623091 (Eli Lilly) and PF-03882845 (Pfizer). In contrast, data from two clinical phase II trials are available for finerenone (Bayer) which demonstrated safety and efficacy in patients with heart failure and additional chronic kidney diseases, and significantly reduced albuminuria in patients with diabetic nephropathy. Neither hyperkalemia nor reductions in kidney function were limiting factors to its use. Novel, nonsteroidal MRAs are currently tested in clinical trials. Based on preclinical and first clinical data, these nonsteroidal MRAs might overcome the limitations of today's steroidal antagonists.

Analytic study on low- external ideal infernal modes in tokamaks with large edge pressure gradients

NASA Astrophysics Data System (ADS)

Brunetti, Daniele; Graves, J. P.; Lazzaro, E.; Mariani, A.; Nowak, S.; Cooper, W. A.; Wahlberg, C.

2018-04-01

The problem of pressure driven infernal type perturbations near the plasma edge is addressed analytically for a circular limited tokamak configuration which presents an edge flattened safety factor. The plasma is separated from a metallic wall, either ideally conducting or resistive, by a vacuum region. The dispersion relation for such types of instabilities is derived and discussed for two classes of equilibrium profiles for pressure and mass density.

Cardiovascular Safety of Biologics and JAK Inhibitors in Patients with Rheumatoid Arthritis.

PubMed

Kang, Eun Ha; Liao, Katherine P; Kim, Seoyoung C

2018-05-30

Increased cardiovascular (CV) risk and associated mortality in rheumatoid arthritis (RA) are not fully explained by traditional CV risk factors. This review discusses the epidemiology and mechanisms of increased CV risk in RA and treatment effects on CV risk focusing on biologic disease-modifying anti-rheumatic drugs (DMARDs) and JAK inhibitors. Intermediary metabolic changes by inflammatory cytokines are observed in body composition, lipid profile, and insulin sensitivity of RA patients, leading to accelerated atherosclerosis and increased CV risk. Successful treatment with DMARDs has shown beneficial effects on these metabolic changes and ultimately CV outcomes, in proportion to the treatment efficacy in general but also with drug-specific mechanisms. Recent data provide further information on comparative CV safety between biologic DMARDs or JAK inhibitors as well as their safety signals for non-atherosclerotic CV events. CV benefits or safety signals associated with DMARD treatments can differ despite similar drug efficacy against RA, suggesting that both anti-inflammatory and drug-specific mechanisms are involved in altering CV risk.

Explosively driven air blast in a conical shock tube

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

Stewart, Joel B., E-mail: joel.b.stewart2.civ@mail.mil; Pecora, Collin, E-mail: collin.r.pecora.civ@mail.mil

2015-03-15

Explosively driven shock tubes present challenges in terms of safety concerns and expensive upkeep of test facilities but provide more realistic approximations to the air blast resulting from free-field detonations than those provided by gas-driven shock tubes. Likewise, the geometry of conical shock tubes can naturally approximate a sector cut from a spherically symmetric blast, leading to a better agreement with the blast profiles of free-field detonations when compared to those provided by shock tubes employing constant cross sections. The work presented in this article documents the design, fabrication, and testing of an explosively driven conical shock tube whose goalmore » was to closely replicate the blast profile seen from a larger, free-field detonation. By constraining the blast through a finite area, large blasts (which can add significant damage and safety constraints) can be simulated using smaller explosive charges. The experimental data presented herein show that a close approximation to the free-field air blast profile due to a 1.5 lb charge of C4 at 76 in. can be achieved by using a 0.032 lb charge in a 76-in.-long conical shock tube (which translates to an amplification factor of nearly 50). Modeling and simulation tools were used extensively in designing this shock tube to minimize expensive fabrication costs.« less

An Airborne Millimeter-Wave FM-CW Radar for Thickness Profiling of Freshwater Ice

DTIC Science & Technology

1992-11-01

commercial and recreational application, including safety and trafficability surveys. A proto- type broadband millimeter wave (26.5 to 40 GHz) Frequency...and utility for ice safety and traffica- appropriate antenna for transmission. Morey (1974) bility studies. Other important applications include...resolution and a 2.7- which can provide reliable safety survey profiling for GHz center frequency, that is capable of airborne pro- the entire practical

21 CFR 601.35 - Evaluation of safety.

Code of Federal Regulations, 2010 CFR

2010-04-01

... established, low-risk profile). Upon reviewing the relevant product characteristics and safety information..., carrier, or ligand; (3) The risks of an incorrect diagnostic determination; (4) The adverse reaction profile of the drug; (5) Results of human experience with the radiopharmaceutical for other uses; and (6...

Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

PubMed

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

2017-01-01

Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.

Exploitation of molecular profiling techniques for GM food safety assessment.

PubMed

Kuiper, Harry A; Kok, Esther J; Engel, Karl-Heinz

2003-04-01

Several strategies have been developed to identify unintended alterations in the composition of genetically modified (GM) food crops that may occur as a result of the genetic modification process. These include comparative chemical analysis of single compounds in GM food crops and their conventional non-GM counterparts, and profiling methods such as DNA/RNA microarray technologies, proteomics and metabolite profiling. The potential of profiling methods is obvious, but further exploration of specificity, sensitivity and validation is needed. Moreover, the successful application of profiling techniques to the safety evaluation of GM foods will require linked databases to be built that contain information on variations in profiles associated with differences in developmental stages and environmental conditions.

Architecture Synthesis and Reduced-Cost Architectures for Human Exploration Missions

NASA Technical Reports Server (NTRS)

Woodcock, Gordon

2004-01-01

Development of architectures for human exploration missions has been pursued in the international aerospace community for a long time. This paper attempts a different approach and way of looking at architectures. Most of the emphasis is on lunar architectures with a brief look at Mars. The first step is to set forth overarching gods in order to understand origins of requirements. Then, principles and guidelines are developed for architecture formulation. It is argued that safety and cost are the primary factors. Alternative mission profiles are examined for adherence to the principles, and specific architectures formulated according to the guidelines. The guidelines themselves indicate preferred evolution paths from lunar to Mars architectures. Results of example calculations are given to illustrate the process, and an evolution path is recommended. Safety and cost criteria tend to conflict, but it is shown that cost-efficient architectures can be enhanced for good safety ratings at modest cost.

[Guidelines in RA treatment: concepts on safety and recommendations using anti-TNF-alpha inhibitors. Grupo de Estudio de Nuevas Terapias de Enfermedades reumáticas (GENTE)].

PubMed

Díaz-Jouanen, Efraín; Abud-Mendoza, Carlos; Garza-Elizondo, Mario Alberto; Medrano-Ramírez, Gabriel; Burgos-Vargas, Rubén; Orozco-Alcalá, José Javier; Pacheco-Tena, César Francisco; Pineda, Carlos; Pozos-Espíndola, Juan Carlos; Ramos-Niembro, Francisco; Robles-San-Román, Manuel; Santana-Sahagún, Jesús Ernesto

2009-01-01

Recommendations for the use of Disease-Modifying Antirheumatic Drugs (DMARD) with both conventional and biological agents in Rheumatoid Arthritis (RA) must be based on their safety profile, adverse effects, risks, and advantages. With the purpose of presenting the most updated information about the safety of tumor necrosis factor alpha (TNFalpha) antagonists, in this article we summarize the literature published during the last three years about this sort of biological agents in specific clinical situations, such as risk of developing infections, cancer, cardiovascular diseases, and autoimmunity; as well as their administration to patients who will undergo surgical procedures, pregnant and/or breast-feeding women, and patients who need immunizations. Likewise, in this analysis we offer specific recommendations, based on evidence, for the best anti-TNF-alfa management.

Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis.

PubMed

Borba, Helena Hiemisch Lobo; Wiens, Astrid; de Souza, Thais Teles; Correr, Cassyano Januário; Pontarolo, Roberto

2014-04-01

The objectives of this study were to evaluate the efficacy, safety, and tolerability of biologic drugs compared with placebo for systemic lupus erythematosus (SLE) treatment. A systematic review evaluating the efficacy and safety of biologic therapies compared with placebo in adult SLE patients treatment was performed. Data from studies performed before September 2013 were collected from several databases (MEDLINE, Cochrane Library, SCIELO, Scopus, and International Pharmaceutical Abstracts). Study eligibility criteria included randomized, double-blind, placebo-controlled trials; regarding treatment with biologic agents in SLE adult patients; and published in English, German, Portuguese, and Spanish. Extracted data were statistically analyzed in a meta-analysis using the Review Manager (RevMan) 5.1 software. Efficacy outcomes included the SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index) score, the SRI (Systemic Lupus Erythematosus Responder Index), normalization of low C3 (<90 mg/dL), anti-double-stranded DNA positive to negative, and no new BILAG (British Isles Lupus Assessment Group index) 1A or 2B flares. Data on safety profile included adverse events, serious and severe adverse events, death, malignancy, infections, and infusion reactions. We also evaluated withdrawals from treatment due to lack of efficacy or adverse events. Thirteen randomized placebo-controlled trials met the criteria for data extraction for systematic review. A meta-analysis regarding the efficacy and safety of belimumab compared with placebo involving four of these trials was undertaken and the remainder contributed to a meta-analysis of the safety of biologic agents. In addition, two trials allowed the performance of a meta-analysis regarding the efficacy and safety of rituximab compared with placebo. Belimumab was more effective than placebo in most evaluated outcomes. No significant differences in the safety and tolerability data were observed between the belimumab and placebo groups. No differences were observed between the rituximab and placebo groups for the efficacy outcomes or safety parameters. Extracted data from the 13 studies were pooled, allowing assessment of the safety of biologic drugs. The meta-analysis revealed a satisfactory safety profile of these agents when used for SLE treatment, as there were no significant differences between the two evaluated groups (biologic agents and placebo) for all outcomes analyzed. Belimumab exhibited a satisfactory profile regarding efficacy, safety, and tolerability. Rituximab showed no superiority over placebo in terms of efficacy, despite its suitable safety profile. Biologic agents exhibited a good safety profile for SLE treatment, indicating that these agents are promising therapies and should be further investigated.

Selective estrogen receptor modulators in clinical practice: a safety overview.

PubMed

Ellis, Amanda J; Hendrick, Vicky M; Williams, Robert; Komm, Barry S

2015-06-01

Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks. This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies. Tamoxifen, a first-generation SERM, is indicated for breast cancer prevention and treatment but is associated with serious safety concerns including endometrial cancer, venous thromboembolic events (VTE), and stroke. Toremifene, raloxifene, bazedoxifene, lasofoxifene, and ospemifene present generally improved, though distinctly different, safety profiles compared with tamoxifen, especially with endometrial cancer and stroke. However, the risk of VTE remains a concern for most SERMs. Each SERM presents a unique risk/benefit profile based on varying indications and tissue-specific ER agonist and antagonist effects, making careful patient selection and ongoing patient monitoring crucial aspects of treatment. Future research may focus on identifying new SERMs for endocrine-resistant and endocrine-responsive cancers and post-menopausal symptoms.

Pharmacodynamic analysis of eribulin safety in breast cancer patients using real-world post-marketing surveillance data.

PubMed

Kawamura, Takahisa; Kasai, Hidefumi; Fermanelli, Valentina; Takahashi, Toshiaki; Sakata, Yukinori; Matsuoka, Toshiyuki; Ishii, Mika; Tanigawara, Yusuke

2018-06-22

Post-marketing surveillance is useful to collect safety data in real-world clinical settings. In this study, we firstly applied the post-marketing real-world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer (RBC/MBC). Demographic and safety data were collected using an active surveillance method from eribulin-treated RBC/MBC patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that may affect the severity of neutropenia were investigated and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were: mean transit time = 104.5 h, neutrophil proliferation rate constant = 0.0377 h -1 , neutrophil elimination rate constant = 0.0295 h -1 , and linear coefficient of drug effect = 0.0413 mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of post-marketing surveillance data to a model-based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Biological Surface Adsorption Index of Nanomaterials: Modelling Surface Interactions of Nanomaterials with Biomolecules.

PubMed

Chen, Ran; Riviere, Jim E

2017-01-01

Quantitative analysis of the interactions between nanomaterials and their surrounding environment is crucial for safety evaluation in the application of nanotechnology as well as its development and standardization. In this chapter, we demonstrate the importance of the adsorption of surrounding molecules onto the surface of nanomaterials by forming biocorona and thus impact the bio-identity and fate of those materials. We illustrate the key factors including various physical forces in determining the interaction happening at bio-nano interfaces. We further discuss the mathematical endeavors in explaining and predicting the adsorption phenomena, and propose a new statistics-based surface adsorption model, the Biological Surface Adsorption Index (BSAI), to quantitatively analyze the interaction profile of surface adsorption of a large group of small organic molecules onto nanomaterials with varying surface physicochemical properties, first employing five descriptors representing the surface energy profile of the nanomaterials, then further incorporating traditional semi-empirical adsorption models to address concentration effects of solutes. These Advancements in surface adsorption modelling showed a promising development in the application of quantitative predictive models in biological applications, nanomedicine, and environmental safety assessment of nanomaterials.

Nonclinical Safety Assessment of Anti-Factor D: Key Strategies and Challenges for the Nonclinical Development of Intravitreal Biologics.

PubMed

Bantseev, Vladimir; Erickson, Rebecca; Leipold, Douglas; Amaya, Caroline; Miller, Paul E; Booler, Helen; Thackaberry, Evan A

The nonclinical toxicology program described here was designed to characterize the safety profile of anti-factor D (AFD; FCFD4514S, lampalizumab) to support intravitreal (ITV) administration in patients with geographic atrophy (GA). The toxicity of AFD was assessed in a single-dose and 6-month repeat-dose study in monkeys at doses up to 10 mg/eye. Toxicity was assessed by clinical ophthalmic examinations, intraocular pressure measurements, ocular photography, electroretinography, fluorescein angiography, optical coherence tomography, and anatomic pathology. Systemic exposure to AFD generally increased with the increase in dose level. The increases in mean maximal concentration and area under the curve values were roughly dose proportional. No accumulation of AFD was observed following 10 doses, and drug exposures were not affected by anti-drug antibodies. AFD was locally and systemically well tolerated in monkeys following ITV doses of up to 10 mg/eye. Ocular effects associated with AFD were limited to transient, reversible, dose-related, aqueous cell responses and injection-related, mild, vitreal cell responses. In the 6-month repeat-dose study, 2 monkeys had a nonspecific immune response to AFD that resulted in severe ocular inflammation, attributed to administration of a heterologous (humanized) protein. The comprehensive toxicology program in monkeys described here was designed to evaluate the safety profile of AFD and to support multiple ITV injections in the clinic. Administration of a heterologous (humanized) protein presents a challenge, and immunogenicity in nonclinical species is not predictive of immunogenicity in humans. Taken together, the results of the nonclinical program described here support the use of AFD in patients with GA.

Bioequivalence between two serum-free recombinant factor VIII preparations (N8 and ADVATE®)--an open-label, sequential dosing pharmacokinetic study in patients with severe haemophilia A.

PubMed

Martinowitz, U; Bjerre, J; Brand, B; Klamroth, R; Misgav, M; Morfini, M; Santagostino, E; Tiede, A; Viuff, D

2011-11-01

Recombinant coagulation factor VIII (rFVIII) concentrates provide a safe and efficacious replacement therapy for treatment and prevention of bleeding in patients with severe haemophilia A. The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of two serum-free rFVIII products: N8, a new rFVIII manufactured by Novo Nordisk and Advate(®), a marketed product. Patients with severe haemophilia A with >150 exposure days to FVIII, without current or past inhibitors, were enrolled in an open-label, first human dose (FHD), multicentre trial. Twenty-three patients first received a single dose of 50 IU kg(-1) body weight Advate(®) followed by 50 IU kg(-1) body weight N8 at the next visit. A 4-day washout period was required prior to each dosing. Blood samples for PK and safety analyses were drawn prior to dosing and at intervals up until 48 h postdosing. The PK parameters were based on FVIII clotting activity (FVIII:C) measurements. Occurrence of adverse events was closely monitored. The mean profiles of FVIII:C and all primary and secondary parameters for Advate(®) and N8 were comparable. The 90% CI for the treatment ratio (Advate(®)/N8) for all primary endpoints (incremental recovery, t(1/2), AUC and Cl), and the secondary endpoints (AUC(last) and C(max)) were within the bioequivalence interval of 0.8-1.25. There were no safety concerns in the study and no reports of inhibitor formation in the 72-h period following exposure to a single N8 dose. In conclusion, N8 is bioequivalent to Advate(®). Furthermore, N8 is well tolerated in the FHD trial. © 2011 Blackwell Publishing Ltd.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

PubMed

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Saturated internal instabilities in advanced-tokamak plasmas

NASA Astrophysics Data System (ADS)

Hua, M.-D.; Chapman, I. T.; Pinches, S. D.; Hastie, R. J.; MAST Team

2010-06-01

"Advanced tokamak" (AT) scenarios were developed with the aim of reaching steady-state operation in future potential tokamak fusion power plants. AT scenarios exhibit non-monotonic to flat safety factor profiles (q, a measure of the magnetic field line pitch), with the minimum q (qmin) slightly above an integer value (qs). However, it has been predicted that these q profiles are unstable to ideal magnetohydrodynamic instabilities as qmin approaches qs. These ideal instabilities, observed and diagnosed as such for the first time in MAST plasmas with AT-like q profiles, have far-reaching consequences like confinement degradation, flattening of the toroidal core rotation or enhanced fast ion losses. These observations motivate the stability analysis of advanced-tokamak plasmas, with a view to provide guidance for stability thresholds in AT scenarios. Additionally, the measured rotation damping is compared to the self-consistently calculated predictions from neoclassical toroidal viscosity theory.

Profile of drowning victims in a coastal community.

PubMed

Nichter, M A; Everett, P B

1989-02-01

Accidental drowning accounts for 15% of all accidental deaths in Pinellas County, Florida, and this study was conducted to better understand the epidemiologic profile of the victim. The medical examiner's records of 230 drownings in Pinellas County from January 1, 1983, through December 31, 1987, were reviewed for demographic and epidemiologic data. Bodies of salt water were the most common drowning site (47%), followed by swimming pools (22%), lakes (11%), baths (7%), and canals (6%). The drowning incidence for males was more than three times that for females. Drowning was endemic among boys less than five years of age (30/100,000/year). Fifty-nine percent of young adult victims had detectable postmortem blood alcohol levels. Drowning rates were highest among children less than five years and adults more than 80 years. Epidemiologic profiles of populations at risk and contributing factors are described and public safety measures are suggested.

Investigating the radial structure of axisymmetric fluctuations in the TCV tokamak with local and global gyrokinetic GENE simulations

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

Merlo, Gabriele; Brunner, Stephan; Huang, Zhouji

Axisymmetric (n=0) density fluctuations measured in the TCV tokamak are observed to possess a frequency f₀ which is either varying (radially dispersive oscillations) or a constant over a large fraction of the plasma minor radius (radially global oscillations) as reported in a companion paper [Z. Huang et al., this issue]. Given that f₀ scales with the sound speed and given the poloidal structure of density fluctuations, these oscillations were interpreted as Geodesic Acoustic Modes, even though f₀ is in fact smaller than the local linear GAM frequency f_GAM . In this work we employ the Eulerian gyrokinetic code GENE tomore » simulate TCV relevant conditions and investigate the nature properties of these oscillations, in particular their relation to the safety factor profile. Local and global simulations are carried out and a good qualitative agreement is observed between experiments and simulations. By varying also the plasma temperature and density profiles, we conclude that a variation of the edge safety factor alone is not sufficient to induce a transition from global to radially inhomogeneous oscillations, as was initially suggested by experimental results. This transition appears instead to be the combined result of variations in the different plasma profiles, collisionality and finite machine size effects. In conclusion, simulations also show that radially global GAM-like oscillations can be observed in all fluxes and fluctuation fields, suggesting that they are the result of a complex nonlinear process involving also finite toroidal mode numbers and not just linear global GAM eigenmodes.« less

Investigating the radial structure of axisymmetric fluctuations in the TCV tokamak with local and global gyrokinetic GENE simulations

DOE PAGES

Merlo, Gabriele; Brunner, Stephan; Huang, Zhouji; ...

2017-12-19

Axisymmetric (n=0) density fluctuations measured in the TCV tokamak are observed to possess a frequency f₀ which is either varying (radially dispersive oscillations) or a constant over a large fraction of the plasma minor radius (radially global oscillations) as reported in a companion paper [Z. Huang et al., this issue]. Given that f₀ scales with the sound speed and given the poloidal structure of density fluctuations, these oscillations were interpreted as Geodesic Acoustic Modes, even though f₀ is in fact smaller than the local linear GAM frequency f_GAM . In this work we employ the Eulerian gyrokinetic code GENE tomore » simulate TCV relevant conditions and investigate the nature properties of these oscillations, in particular their relation to the safety factor profile. Local and global simulations are carried out and a good qualitative agreement is observed between experiments and simulations. By varying also the plasma temperature and density profiles, we conclude that a variation of the edge safety factor alone is not sufficient to induce a transition from global to radially inhomogeneous oscillations, as was initially suggested by experimental results. This transition appears instead to be the combined result of variations in the different plasma profiles, collisionality and finite machine size effects. In conclusion, simulations also show that radially global GAM-like oscillations can be observed in all fluxes and fluctuation fields, suggesting that they are the result of a complex nonlinear process involving also finite toroidal mode numbers and not just linear global GAM eigenmodes.« less

Establishment of a New Quality Control and Vaccine Safety Test for Influenza Vaccines and Adjuvants Using Gene Expression Profiling

PubMed Central

Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

2015-01-01

We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. PMID:25909814

Safety of Abiraterone Acetate in Castration-resistant Prostate Cancer Patients With Concomitant Cardiovascular Risk Factors.

PubMed

Procopio, Giuseppe; Grassi, Paolo; Testa, Isabella; Verzoni, Elena; Torri, Valter; Salvioni, Roberto; Valdagni, Riccardo; de Braud, Filippo

2015-10-01

The aim of this study was to evaluate the safety profile of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) men with cardiovascular comorbidity, as little conclusive safety data are available in this patient subset. A retrospective analysis of mCRPC patients with controlled cardiovascular comorbidities, receiving AA 1000 mg administered orally once daily and prednisone 5 mg twice daily, between April 2011 and July 2012, was performed. All clinical and instrumental variables and toxicity data were analyzed by descriptive statistics: mean, standard deviation, minimum and maximum values for continuous variables, and absolute and relative frequencies for categorical variables. A total of 51 mCRPC patients were evaluated. Metastatic sites included the bone (74%), lungs, and liver (26%). All patients were previously treated with at least 2 lines of hormone and 1 docetaxel-based chemotherapy. Preexisting cardiac risk factors included hypertension (41%), cardiac ischemia (12%), arrhythmias (6%), dislipidemia (18%), and hyperglycemia (30%). No grade 3-4 adverse events were observed. Grade 1-2 adverse events included fluid retention (18%), asthenia (15%), and hypertension (16%). Median progression-free survival was 5.1 months (95% confidence interval, 0.5-12). Prostate specific antigen assessment revealed a good overall disease control rate (64%). AA appears to be safe and well tolerated even in patients with cardiovascular comorbidities or with increased risk factors for cardiovascular diseases.

Development of a new virtual diagnostic for V3FIT

NASA Astrophysics Data System (ADS)

Trevisan, G. L.; Cianciosa, M. R.; Terranova, D.; Hanson, J. D.

2014-12-01

The determination of plasma equilibria from diagnostic information is a fundamental issue. V3FIT is a fully three-dimensional reconstruction code capable of solving the inverse problem using both magnetic and kinetic measurements. It uses VMEC as core equilibrium solver and supports both free- and fixed-boundary reconstruction approaches. In fixed-boundary mode VMEC does not use explicit information about currents in external coils, even though it has important effects on the shape of the safety factor profile. Indeed, the edge safety factor influences the reversal position in RFP plasmas, which then determines the position of the m = 0 island chain and the edge transport properties. In order to exploit such information a new virtual diagnostic has been developed, that thanks to Ampère's law relates the external current through the center of the torus to the circulation of the toroidal magnetic field on the outermost flux surface. The reconstructions that exploit the new diagnostic are indeed found to better interpret the experimental data with respect to edge physics.

Assessment of liquefaction potential index for Mumbai city

NASA Astrophysics Data System (ADS)

Dixit, J.; Dewaikar, D. M.; Jangid, R. S.

2012-09-01

Mumbai city is the financial capital of India and is fifth most densely populated city in the world. Seismic soil liquefaction is evaluated for Mumbai city in terms of the factors of safety against liquefaction (FS) along the depths of soil profiles for different earthquakes with 2% probability of exceedance in 50 yr using standard penetration test (SPT)-based simplified empirical procedure. This liquefaction potential is evaluated at 142 representative sites in the city using the borehole records from standard penetration tests. Liquefaction potential index (LPI) is evaluated at each borehole location from the obtained factors of safety (FS) to predict the potential of liquefaction to cause damage at the surface level at the site of interest. Spatial distribution of soil liquefaction potential is presented in the form of contour maps of LPI values. As the majority of the sites in the city are of reclaimed land, the vulnerability of liquefaction is observed to be very high at many places.

European consumer response to packaging technologies for improved beef safety.

PubMed

Van Wezemael, Lynn; Ueland, Øydis; Verbeke, Wim

2011-09-01

Beef packaging can influence consumer perceptions of beef. Although consumer perceptions and acceptance are considered to be among the most limiting factors in the application of new technologies, there is a lack of knowledge about the acceptability to consumers of beef packaging systems aimed at improved safety. This paper explores European consumers' acceptance levels of different beef packaging technologies. An online consumer survey was conducted in five European countries (n=2520). Acceptance levels among the sample ranged between 23% for packaging releasing preservative additives up to 73% for vacuum packaging. Factor analysis revealed that familiar packaging technologies were clearly preferred over non-familiar technologies. Four consumer segments were identified: the negative (31% of the sample), cautious (30%), conservative (17%) and enthusiast (22%) consumers, which were profiled based on their attitudes and beef consumption behaviour. Differences between consumer acceptance levels should be taken into account while optimising beef packaging and communicating its benefits. Copyright © 2011 Elsevier Ltd. All rights reserved.

Safety profile: fifteen years of clinical experience with ibuprofen.

PubMed

Royer, G L; Seckman, C E; Welshman, I R

1984-07-13

Since its introduction in the United States in 1974, ibuprofen (Motrin, Upjohn) has been shown to be safe and effective for the treatment of pain, dysmenorrhea, inflammation, and fever. A careful review of pre-registration and postmarketing data from both patients and normal subjects clearly indicates ibuprofen's remarkable safety profile compared with that of aspirin and other commonly prescribed nonsteroidal anti-inflammatory agents. Continued safety can be anticipated on the basis of the past 15 years of review experience.

Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis

PubMed Central

Inomata, Minoru; Nishioka, Yasuhiko; Azuma, Arata

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis. The molecular mechanisms involved in the progression of IPF are not fully understood; however, the platelet-derived growth factor (PDGF)/PDGF receptor pathway is thought to play a critical role in fibrogenesis of the lungs. Other growth factors, including fibroblast growth factor and vascular endothelial growth factor, are also thought to contribute to the pathogenesis of pulmonary fibrosis. Nintedanib is an inhibitor of multiple tyrosine kinases, including receptors for PDGF, fibroblast growth factor, and vascular endothelial growth factor. In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily. Pirfenidone, another antifibrotic drug, was shown to limit the decline in pulmonary function in patients with IPF in the ASCEND trial. Combination therapy with nintedanib and pirfenidone is anticipated, although further evaluation of its long-term safety is needed. There is limited evidence for the safety of the combination therapy although a Phase II trial conducted in Japan demonstrated that combination therapy with nintedanib and pirfenidone was tolerable for 1 month. Available antifibrotic agents (ie, pirfenidone and N-acetylcysteine) have limited efficacy as single therapies for IPF; therefore, further study of combination therapy with antifibrotic agents is needed. PMID:26346347

Analysis of the Japanese subgroup in LEOPOLD II: a phase 2/3 study of BAY 81-8973, a new recombinant factor VIII product.

PubMed

Fujii, Teruhisa; Hanabusa, Hideji; Shima, Midori; Morinaga, Takeshi; Fukutake, Katsuyuki

2017-03-01

BAY 81-8973, a new full length recombinant FVIII product, has been developed for prophylaxis and on-demand therapy in patients with hemophilia A. LEOPOLD II was a phase 2/3 study comparing prophylaxis versus on-demand treatment with BAY 81-8973. The analysis herein evaluated the clinical profile in Japanese subjects enrolled in LEOPOLD II. The LEOPOLD II was an open-label randomized crossover study. Our analysis evaluated the efficacy using the annualized bleeding rate, safety, and pharmacokinetics in Japanese subjects with severe hemophilia A enrolled in LEOPOLD II. The median annualized bleeding rate was 59.9/year in the on-demand group and 1.9/year in the prophylaxis group for Japanese subjects. There were no study drug-related adverse events in the Japanese subjects. None of the subjects developed FVIII inhibitors. There were no apparent clinical differences in efficacy, safety, and pharmacokinetics between the Japanese and the non-Japanese subjects. Data for the Japanese subjects showed annualized bleeding rates to be remarkably lower in the prophylaxis group compared to the on-demand group and that BAY 81-8973 exhibited a good safety profile and tolerability. These results were similar for the non-Japanese subjects. The results support adoption of BAY 81-8973 for treatment of Japanese subjects with severe hemophilia A.

Methods to Prepare Aluminum Salt-Adjuvanted Vaccines.

PubMed

Thakkar, Sachin G; Cui, Zhengrong

2017-01-01

Many human vaccines contain certain insoluble aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate as vaccine adjuvants to boost the immunogenicity of the vaccines. Aluminum salts have been used as vaccine adjuvants for decades and have an established, favorable safety profile. However, preparing aluminum salts and aluminum salt-adjuvanted vaccines in a consistent manner remains challenging. This chapter discusses methods to prepare aluminum salts and aluminum salt-adjuvanted vaccines, factors to consider during preparation, and methods to characterize the vaccines after preparation.

The effect of internal magnetic structure on the fishbone instability

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

Roberts, D.W.; Powell, E.; Kaita, R.

1992-01-01

Plasmas exhibiting the ``fishbone`` instability studied on the PBX-M tokamak show a distinct relationship between the plasma shape, the internal magnetic structure, and the presence or absence of fast ion losses associated with the fishbone mode. We have, for the first time, carried out measurements of the magnetic safety factor profile in fishbone-unstable plasmas, and used the knowledge of the associated experimental equilibria to compare the stability and fast ion loss properties of these plasmas with experimental observations.

The effect of internal magnetic structure on the fishbone instability

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

Roberts, D.W.; Powell, E.; Kaita, R.

1992-01-01

Plasmas exhibiting the fishbone'' instability studied on the PBX-M tokamak show a distinct relationship between the plasma shape, the internal magnetic structure, and the presence or absence of fast ion losses associated with the fishbone mode. We have, for the first time, carried out measurements of the magnetic safety factor profile in fishbone-unstable plasmas, and used the knowledge of the associated experimental equilibria to compare the stability and fast ion loss properties of these plasmas with experimental observations.

Cardiac rehabilitation: a comprehensive review

PubMed Central

Lear, Scott A; Ignaszewski, Andrew

2001-01-01

Cardiac rehabilitation (CR) is a commonly used treatment for men and women with cardiovascular disease. To date, no single study has conclusively demonstrated a comprehensive benefit of CR. Numerous individual studies, however, have demonstrated beneficial effects such as improved risk-factor profile, slower disease progression, decreased morbidity, and decreased mortality. This paper will review the evidence for the use of CR and discuss the implications and limitations of these studies. The safety, relevance to special populations, challenges, and future directions of CR will also be reviewed. PMID:11806801

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach.

PubMed

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg(-1) day(-1) or 250 mg kg(-1) day(-1) for a period of 7 days (n=4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers. Copyright 2009 Elsevier B.V. All rights reserved.

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-08-01

We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. Seven RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics. © 2016 Pharmacotherapy Publications, Inc.

Stereotactic body radiotherapy (SBRT) for multiple pulmonary oligometastases: Analysis of number and timing of repeat SBRT as impact factors on treatment safety and efficacy.

PubMed

Klement, R J; Hoerner-Rieber, J; Adebahr, S; Andratschke, N; Blanck, O; Boda-Heggemann, J; Duma, M; Eble, M J; Eich, H C; Flentje, M; Gerum, S; Hass, P; Henkenberens, C; Hildebrandt, G; Imhoff, D; Kahl, K H; Klass, N D; Krempien, R; Lohaus, F; Petersen, C; Schrade, E; Wendt, T G; Wittig, A; Guckenberger, M

2018-03-03

Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Final quality of life and safety data for patients with metastatic castration-resistant prostate cancer treated with cabazitaxel in the UK Early Access Programme (EAP) (NCT01254279).

PubMed

Bahl, Amit; Masson, Susan; Malik, Zafar; Birtle, Alison J; Sundar, Santhanam; Jones, Rob J; James, Nicholas D; Mason, Malcolm D; Kumar, Satish; Bottomley, David; Lydon, Anna; Chowdhury, Simon; Wylie, James; de Bono, Johann S

2015-12-01

To compile the safety profile and quality of life (QoL) data for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel in the UK Early Access Programme (UK EAP). A total of 112 patients participated at 12 UK cancer centres. All had mCRPC with disease progression during or after docetaxel. Patients received cabazitaxel 25 mg/m(2) every 3 weeks with prednisolone 10 mg daily for up to 10 cycles. Safety assessments were performed before each cycle and QoL was recorded at alternate cycles using the EQ-5D-3L questionnaire and visual analogue scale (VAS). The safety profile was compiled after completion of the UK EAP and QoL measures were analysed to record trends. No formal statistical analysis was carried out. The incidences of neutropenic sepsis (6.3%), grade 3 and 4 diarrhoea (4.5%) and grade 3 and 4 cardiac toxicity (0%) were low. Neutropenic sepsis episodes, though low, occurred only in patients who did not receive prophylactic granulocyte-colony stimulating factor. There were trends towards improved VAS and EQ-5D-3L pain scores during treatment. The UK EAP experience indicates that cabazitaxel might improve QoL in mCRPC and represents an advance and a useful addition to the armamentarium of treatment for patients whose disease has progressed during or after docetaxel. In view of the potential toxicity, careful patient selection is important. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Differential Adjustment Among Rural Adolescents Exposed to Family Violence

PubMed Central

Sianko, Natallia; Hedge, Jasmine M.; McDonell, James R.

2016-01-01

This study examines differences in psychological adjustment in a sample of rural adolescents who have been exposed to family violence. Self-report questionnaires were administered to 580 adolescents and their primary caregivers. The results revealed that over two thirds of the study participants (68.8%) had been exposed to violence in their families. As hypothesized, cluster analysis identified several profiles among adolescents, distinguished by their psychological and emotional functioning: well adjusted (46.2%), moderately adjusted (44.3%), and struggling (9.5%). Discriminant function analysis confirmed the groupings and revealed that family functioning was among the most influential factors explaining adjustment differences. Multivariate analyses of variance (MANOVAs) further showed that adolescents from each of the three adjustment profiles reported significantly different levels of family social support, parental involvement, and perceived neighborhood safety. Overall, the results confirm heterogeneity of adolescent adaptation in the aftermath of family violence and provide insights into family and neighborhood factors that account for variability in adolescents’ reactions to violence. Implications for future research and practical interventions are discussed. PMID:27106255

History of safe use as applied to the safety assessment of novel foods and foods derived from genetically modified organisms.

PubMed

Constable, A; Jonas, D; Cockburn, A; Davi, A; Edwards, G; Hepburn, P; Herouet-Guicheney, C; Knowles, M; Moseley, B; Oberdörfer, R; Samuels, F

2007-12-01

Very few traditional foods that are consumed have been subjected to systematic toxicological and nutritional assessment, yet because of their long history and customary preparation and use and absence of evidence of harm, they are generally regarded as safe to eat. This 'history of safe use' of traditional foods forms the benchmark for the comparative safety assessment of novel foods, and of foods derived from genetically modified organisms. However, the concept is hard to define, since it relates to an existing body of information which describes the safety profile of a food, rather than a precise checklist of criteria. The term should be regarded as a working concept used to assist the safety assessment of a food product. Important factors in establishing a history of safe use include: the period over which the traditional food has been consumed; the way in which it has been prepared and used and at what intake levels; its composition and the results of animal studies and observations from human exposure. This paper is aimed to assist food safety professionals in the safety evaluation and regulation of novel foods and foods derived from genetically modified organisms, by describing the practical application and use of the concept of 'history of safe use'.

Profile control simulations and experiments on TCV: a controller test environment and results using a model-based predictive controller

NASA Astrophysics Data System (ADS)

Maljaars, E.; Felici, F.; Blanken, T. C.; Galperti, C.; Sauter, O.; de Baar, M. R.; Carpanese, F.; Goodman, T. P.; Kim, D.; Kim, S. H.; Kong, M.; Mavkov, B.; Merle, A.; Moret, J. M.; Nouailletas, R.; Scheffer, M.; Teplukhina, A. A.; Vu, N. M. T.; The EUROfusion MST1-team; The TCV-team

2017-12-01

The successful performance of a model predictive profile controller is demonstrated in simulations and experiments on the TCV tokamak, employing a profile controller test environment. Stable high-performance tokamak operation in hybrid and advanced plasma scenarios requires control over the safety factor profile (q-profile) and kinetic plasma parameters such as the plasma beta. This demands to establish reliable profile control routines in presently operational tokamaks. We present a model predictive profile controller that controls the q-profile and plasma beta using power requests to two clusters of gyrotrons and the plasma current request. The performance of the controller is analyzed in both simulation and TCV L-mode discharges where successful tracking of the estimated inverse q-profile as well as plasma beta is demonstrated under uncertain plasma conditions and the presence of disturbances. The controller exploits the knowledge of the time-varying actuator limits in the actuator input calculation itself such that fast transitions between targets are achieved without overshoot. A software environment is employed to prepare and test this and three other profile controllers in parallel in simulations and experiments on TCV. This set of tools includes the rapid plasma transport simulator RAPTOR and various algorithms to reconstruct the plasma equilibrium and plasma profiles by merging the available measurements with model-based predictions. In this work the estimated q-profile is merely based on RAPTOR model predictions due to the absence of internal current density measurements in TCV. These results encourage to further exploit model predictive profile control in experiments on TCV and other (future) tokamaks.

Practical aspects of instrumentation system installation, volume 13

NASA Technical Reports Server (NTRS)

Borek, R. W.; Pool, A. (Editor); Sanderson, K. C. (Editor)

1981-01-01

A review of factors influencing installation of aircraft flight test instrumentation is presented. Requirements, including such factors as environment, reliability, maintainability, and system safety are discussed. The assessment of the mission profile is followed by an overview of electrical and mechanical installation factors with emphasis on shock/vibration isolation systems and standardization of the electric wiring installation, two factors often overlooked by instrumentation engineers. A discussion of installation hardware reviews the performance capabilities of wiring, connectors, fuses and circuit breakers, and a guide to proper selections is provided. The discussion of the installation is primarily concerned with the electrical wire routing, shield terminations and grounding. Also inclued are some examples of installation mistakes that could affect system accuracy. System verification procedures and special considerations such as sneak circuits, pyrotechnics, aircraft antenna patterns, and lightning strikes are discussed.

Model equations for the Eiffel Tower profile: historical perspective and new results

NASA Astrophysics Data System (ADS)

Weidman, Patrick; Pinelis, Iosif

2004-07-01

Model equations for the shape of the Eiffel Tower are investigated. One model purported to be based on Eiffel's writing does not give a tower with the correct curvature. A second popular model not connected with Eiffel's writings provides a fair approximation to the tower's skyline profile of 29 contiguous panels. Reported here is a third model derived from Eiffel's concern about wind loads on the tower, as documented in his communication to the French Civil Engineering Society on 30 March 1885. The result is a nonlinear, integro-differential equation which is solved to yield an exponential tower profile. It is further verified that, as Eiffel wrote, "in reality the curve exterior of the tower reproduces, at a determined scale, the same curve of the moments produced by the wind". An analysis of the actual tower profile shows that it is composed of two piecewise continuous exponentials with different growth rates. This is explained by specific safety factors for wind loading that Eiffel & Company incorporated in the design of the free-standing tower. To cite this article: P. Weidman, I. Pinelis, C. R. Mecanique 332 (2004).

Identification of an essential virulence gene of cyprinid herpesvirus 3.

PubMed

Boutier, Maxime; Gao, Yuan; Vancsok, Catherine; Suárez, Nicolás M; Davison, Andrew J; Vanderplasschen, Alain

2017-09-01

The genus Cyprinivirus consists of a growing list of phylogenetically related viruses, some of which cause severe economic losses to the aquaculture industry. The archetypal member, cyprinid herpesvirus 3 (CyHV-3) causes mass mortalities worldwide in koi and common carp. A CyHV-3 mutant was described previously that is attenuated in vivo by a deletion affecting two genes (ORF56 and ORF57). The relative contributions of ORF56 and ORF57 to the safety and efficacy profile of this vaccine candidate have now been assessed by analysing viruses individually deleted for ORF56 or ORF57. Inoculation of these viruses into carp demonstrated that the absence of ORF56 did not affect virulence, whereas the absence of ORF57 led to an attenuation comparable to, though slightly less than, that of the doubly deleted virus. To demonstrate further the role of ORF57 as a key virulence factor, a mutant retaining the ORF57 region but unable to express the ORF57 protein was produced by inserting multiple in-frame stop codons into the coding region. Analysis of this virus in vivo revealed a safety and efficacy profile comparable to that of the doubly deleted virus. These findings show that ORF57 encodes an essential CyHV-3 virulence factor. They also indicate that ORF57 orthologues in other cypriniviruses may offer promising targets for the rational design of attenuated recombinant vaccines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Astronaut Risk Levels During Crew Module (CM) Land Landing

NASA Technical Reports Server (NTRS)

Lawrence, Charles; Carney, Kelly S.; Littell, Justin

2007-01-01

The NASA Engineering Safety Center (NESC) is investigating the merits of water and land landings for the crew exploration vehicle (CEV). The merits of these two options are being studied in terms of cost and risk to the astronauts, vehicle, support personnel, and general public. The objective of the present work is to determine the astronaut dynamic response index (DRI), which measures injury risks. Risks are determined for a range of vertical and horizontal landing velocities. A structural model of the crew module (CM) is developed and computational simulations are performed using a transient dynamic simulation analysis code (LS-DYNA) to determine acceleration profiles. Landing acceleration profiles are input in a human factors model that determines astronaut risk levels. Details of the modeling approach, the resulting accelerations, and astronaut risk levels are provided.

Dimensions of driving anger and their relationships with aberrant driving.

PubMed

Zhang, Tingru; Chan, Alan H S; Zhang, Wei

2015-08-01

The purpose of this study was to investigate the relationship between driving anger and aberrant driving behaviours. An internet-based questionnaire survey was administered to a sample of Chinese drivers, with driving anger measured by a 14-item short Driving Anger Scale (DAS) and the aberrant driving behaviours measured by a 23-item Driver Behaviour Questionnaire (DBQ). The results of Confirmatory Factor Analysis demonstrated that the three-factor model (hostile gesture, arrival-blocking and safety-blocking) of the DAS fitted the driving anger data well. The Exploratory Factor Analysis on DBQ data differentiated four types of aberrant driving, viz. emotional violation, error, deliberate violation and maintaining progress violation. For the anger-aberration relation, it was found that only "arrival-blocking" anger was a significant positive predictor for all four types of aberrant driving behaviours. The "safety-blocking" anger revealed a negative impact on deliberate violations, a finding different from previously established positive anger-aberration relation. These results suggest that drivers with different patterns of driving anger would show different behavioural tendencies and as a result intervention strategies may be differentially effective for drivers of different profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

States Respond to School Safety Concerns with 2013 Legislation. School Safety: 2013 Legislative Session

ERIC Educational Resources Information Center

Wixom, Micah Ann

2014-01-01

School safety policies are constantly evolving, often in response to fatal events. After several high-profile and tragic shootings over the past 15 years, school safety has become a major focus for parents, school officials, policymakers and the public nationwide. ECS [Education Commission of the States] conducted a scan of school safety-related…

An evaluation of two conducted electrical weapons and two probe designs using a swine comparative cardiac safety model.

PubMed

Dawes, Donald Murray; Ho, Jeffrey D; Moore, Johanna C; Miner, James R

2013-09-01

Despite human laboratory and field studies that have demonstrated a reasonable safety profile for TASER brand conducted electrical weapons (CEW), the results of some swine studies and arrest related deaths temporal to the use of the CEWs continue to raise questions regarding cardiac safety. TASER International, Inc., has released a new CEW, the TASER X2, touted to have a better safety profile than its long-standing predecessor, the TASER X26. We have developed a model to assess the relative cardiac safety of CEWs and used it to compare the TASER X2 and the TASER X26. This safety model was also used to assess the relative safety of an experimental probe design as compared to the standard steel probe. Our results suggest that the TASER X2 has an improved safety margin over the TASER X26. The new probe design also has promise for enhanced cardiac safety, although may have some disadvantages when compared to the existing design which would make field use impractical.

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers

PubMed Central

Anderlini, Paolo

2015-01-01

Purpose of Review Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. Recent Findings In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. G-CSF receptors were identified in a variety of non-myeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for PBPCs, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. Summary rhG-CSF effects in healthy volunteers, while normally transient and self-limiting, are now believed to be more complex and heterogeneous that previously thought. While rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals. PMID:19057203

Safety profile of levetiracetam.

PubMed

Arroyo, Santiago; Crawford, Pamela

2003-05-01

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

Denosumab for the Treatment of Osteoporosis

PubMed Central

Zaheer, Sarah; LeBoff, Meryl; Lewiecki, E. Michael

2015-01-01

Introduction Low trauma fractures due to osteoporosis are a major health concern worldwide. Despite the availability of many therapeutic compounds to reduce fracture risk, osteoporosis remains undertreated and the burden of osteoporotic fractures remains high. Denosumab is a novel agent that acts to reduce bone turnover, improve bone mineral density, and reduce fracture risk, offering a favorable efficacy and safety profile. Areas covered This review covers the pharmacology and major clinical trials with extension/post-marketing follow-up, including trials for all FDA-approved indications of denosumab to date. Expert Opinion Denosumab is an efficacious and safe osteoporosis treatment option, with current data up to 8 years of continued use showing continued improvement in bone density with sustained fracture risk reduction. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Future considerations include safety of prolonged treatment beyond 8 years, and efficacy/fracture risk after discontinuation or with non-adherence, given the characteristic pharmacodynamic profile of denosumab. PMID:25614274

Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method] demonstrates efficacy, safety and low-risk for immunogenicity in routine clinical practice.

PubMed

Oldenburg, J; Goudemand, J; Valentino, L; Richards, M; Luu, H; Kriukov, A; Gajek, H; Spotts, G; Ewenstein, B

2010-11-01

  Postauthorization safety surveillance of factor VIII (FVIII) concentrates is essential for assessing rare adverse event incidence. We determined safety and efficacy of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method, (rAHF-PFM)] during routine clinical practice. Subjects with differing haemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. Among 408 evaluable subjects, 386 (95%) received excellent/good efficacy ratings for all on-demand assessments; the corresponding number for subjects with previous FVIII inhibitors was 36/41 (88%). Among 276 evaluable subjects receiving prophylaxis continuously in the study, 255 (92%) had excellent/good ratings for all prophylactic assessments; the corresponding number for subjects with previous FVIII inhibitors was 41/46 (89%). Efficacy of surgical prophylaxis was excellent/good in 16/16 evaluable procedures. Among previously treated patients (PTPs) with >50 exposure days (EDs) and FVIII≤2%, three (0.75%) developed low-titre inhibitors. Two of these subjects had a positive inhibitor history; thus, the incidence of de novo inhibitor formation in PTPs with FVIII≤2% and no inhibitor history was 1/348 (0.29%; 95% CI, 0.01-1.59%). A PTP with moderate haemophilia developed a low-titre inhibitor. High-titre inhibitors were reported in a PTP with mild disease (following surgery), a previously untreated patient (PUP) with moderate disease (following surgery) and a PUP with severe disease. The favourable benefit/risk profile of rAHF-PFM previously documented in prospective clinical trials has been extended to include a broader range of haemophilia patients, many of whom would have been ineligible for registration studies. © 2010 Blackwell Publishing Ltd.

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes

PubMed Central

Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

2016-01-01

Objective. Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. Methods. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. Results. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. Conclusion. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. Trial registration: ClincialTrials.gov, clinicaltrials.gov, NCT00069329 PMID:27143789

Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma.

PubMed

Courtney, Kevin D; Infante, Jeffrey R; Lam, Elaine T; Figlin, Robert A; Rini, Brian I; Brugarolas, James; Zojwalla, Naseem J; Lowe, Ann M; Wang, Keshi; Wallace, Eli M; Josey, John A; Choueiri, Toni K

2018-03-20

Purpose The von Hippel-Lindau tumor suppressor is inactivated in the majority of clear cell renal cell carcinomas (ccRCCs), leading to inappropriate stabilization of hypoxia-inducible factor-2α (HIF-2α). PT2385 is a first-in-class HIF-2α antagonist. Objectives of this first-in-human study were to characterize the safety, pharmacokinetics, pharmacodynamics, and efficacy, and to identify the recommended phase II dose (RP2D) of PT2385. Patients and Methods Eligible patients had locally advanced or metastatic ccRCC that had progressed during one or more prior regimens that included a vascular endothelial growth factor inhibitor. PT2385 was administered orally at twice-per-day doses of 100 to 1,800 mg, according to a 3 + 3 dose-escalation design, followed by an expansion phase at the RP2D. Results The dose-escalation and expansion phases enrolled 26 and 25 patients, respectively. Patients were heavily pretreated, with a median of four (range, one to seven) prior therapies. No dose-limiting toxicity was observed at any dose. On the basis of safety, pharmacokinetic, and pharmacodynamic profiling, the RP2D was defined as 800 mg twice per day. PT2385 was well tolerated, with anemia (grade 1 to 2, 35%; grade 3, 10%), peripheral edema (grade 1 to 2, 37%; grade 3, 2%), and fatigue (grade 1 to 2, 37%; no grade 3 or 4) being the most common treatment-emergent adverse events. No patients discontinued treatment because of adverse events. Complete response, partial response, and stable disease as best response were achieved by 2%, 12%, and 52% of patients, respectively. At data cutoff, eight patients remained in the study, with 13 patients in the study for ≥ 1 year. Conclusion PT2385 has a favorable safety profile and is active in patients with heavily pretreated ccRCC, validating direct HIF-2α antagonism for the treatment of patients with ccRCC.

Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516.

PubMed

Lagu, Bharat; Kluge, Arthur F; Goddeeris, Matthew M; Tozzo, Effie; Fredenburg, Ross A; Chellur, Shekar; Senaiar, Ramesh S; Jaleel, Mahaboobi; Babu, D Ravi Krishna; Tiwari, Nirbhay K; Takahashi, Taisuke; Patane, Michael A

2017-11-04

Compound 1 regulates significantly fewer genes than the PPARδ modulator, GW501516. Both compounds are efficacious in a thermal injury model of muscle regeneration. The restricted gene profile of 1 relative to GW501516 suggests that 1 may be pharmacoequivalent to GW501516 with fewer PPAR-related safety concerns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

PubMed Central

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. PMID:28721057

Apatinib for the treatment of gastric cancer.

PubMed

Roviello, Giandomenico; Ravelli, Andrea; Fiaschi, Anna Ida; Cappelletti, Maria Rosa; Gobbi, Angela; Senti, Chiara; Zanotti, Laura; Polom, Karol; Reynolds, Andrew R; Fox, Stephen B; Generali, Daniele

2016-08-01

Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cancer.

A risk microbiological profile of the Australian red meat industry: risk ratings of hazard-product pairings.

PubMed

Sumner, John; Ross, Tom; Jenson, Ian; Pointon, Andrew

2005-11-25

A risk profile of microbial hazards across the supply continuum for the beef, sheep and goat meat industries was developed using both a qualitative tool and a semi-quantitative, spreadsheet tool, Risk Ranger. The latter is useful for highlighting factors contributing to food safety risk and for ranking the risk of various product/pathogen combinations. In the present profile the qualitative tool was used as a preliminary screen for a wide range of hazard-product pairings while Risk Ranger was used to rank in order of population health risk pairings for which quantitative data were available and for assessing the effect of hypothetical scenarios. 'High' risk hazard-product pairings identified were meals contaminated with Clostridium perfringens provided by caterers which have not implemented HACCP; kebabs cross-contaminated by Salmonella present in drip trays or served undercooked; meals served in the home cross-contaminated with Salmonella. 'Medium' risk hazard-product pairings identified were ready-to-eat meats contaminated with Listeria monocytogenes and which have extended shelf life; Uncooked Comminuted Fermented Meat (UCFM)/Salami contaminated with Enterohaemorrhagic E. coli (EHEC) and Salmonella; undercooked hamburgers contaminated with EHEC; kebabs contaminated by Salmonella under normal production or following final "flash" heating. Identified 'low' risk hazard-product pairings included cooked, ready-to-eat sausages contaminated with Salmonella; UCFM/Salami contaminated with L. monocytogenes; well-cooked hamburgers contaminated with EHEC. The risk profile provides information of value to Australia's risk managers in the regulatory, processing and R&D sectors of the meat and meat processing industry for the purposes of identifying food safety risks in the industry and for prioritising risk management actions.

Factors discriminating among profiles of resilience and psychopathology in children exposed to intimate partner violence (IPV).

PubMed

Graham-Bermann, Sandra A; Gruber, Gabrielle; Howell, Kathryn H; Girz, Laura

2009-09-01

To evaluate the social and emotional adjustment of 219 children in families with varying levels of intimate partner violence (IPV) using a model of risk and protection. To explore factors that differentiate children with poor adjustment from those with resilience. Mothers who experienced IPV in the past year and their children ages 6-12 were interviewed. Standardized measures assessed family violence, parenting, family functioning, maternal mental health, and children's adjustment and beliefs. Using cluster analysis, all cases with valid data on the Child Behavior Checklist, Child Depression Inventory, General Self-Worth and Social Self-Competence measures were described by four profiles of children's adjustment: Severe Adjustment Problems (24%); children who were Struggling (45%); those with Depression Only (11%); and Resilient (20%) with high competence and low adjustment problems. Multinomial logistic regression analyses showed children in the Severe Problems cluster witnessed more family violence and had mothers higher in depression and trauma symptoms than other children. Resilient and Struggling children had mothers with better parenting, more family strengths and no past violent partner. Parents of children with Severe Problems were lacking these attributes. The Depressed profile children witnessed less violence but had greater fears and worries about mother's safety. Factors related to the child, to the mother and to the family distinguish different profiles of adjustment for children exposed to IPV who are living in the community. Resilient children have less violence exposure, fewer fears and worries, and mothers with better mental health and parenting skills, suggesting avenues for intervention with this population. Findings suggest that child adjustment is largely influenced by parent functioning. Thus, services should be targeted at both the child and the parent. Clinical interventions shaped to the unique needs of the child might also be tested with this population.

Evaluation of pedestrian safety at intersections: A theoretical framework based on pedestrian-vehicle interaction patterns.

PubMed

Ni, Ying; Wang, Menglong; Sun, Jian; Li, Keping

2016-11-01

Pedestrians are the most vulnerable road users, and pedestrian safety has become a major research focus in recent years. Regarding the quality and quantity issues with collision data, conflict analysis using surrogate safety measures has become a useful method to study pedestrian safety. However, given the inequality between pedestrians and vehicles in encounters and the multiple interactions between pedestrians and vehicles, it is insufficient to simply use the same indicator(s) or the same way to aggregate indicators for all conditions. In addition, behavioral factors cannot be neglected. To better use information extracted from trajectories for safety evaluation and pay more attention on effects of behavioral factors, this paper develops a more sophisticated framework for pedestrian conflict analysis that takes pedestrian-vehicle interactions into consideration. A concept of three interaction patterns has been proposed for the first time, namely "hard interaction," "no interaction," and "soft-interaction." Interactions have been categorized under one of these patterns by analyzing profiles of speed and conflict indicators during the whole interactive processes. In this paper, a support vector machine (SVM) approach has been adopted to classify severity levels for a dataset including 1144 events extracted from three intersections in Shanghai, China, followed by an analysis of variable importance. The results revealed that different conflict indicators have different contributions to indicating the severity level under various interaction patterns. Therefore, it is recommended either to use specific conflict indicators or to use weighted indicator aggregation for each interaction pattern when evaluating pedestrian safety. The implementation has been carried out at the fourth crosswalk, and the results indicate that the proposed method can achieve a higher accuracy and better robustness than conventional methods. Furthermore, the method is helpful for better understanding underlying levels of safety from the behavioral perspective, which can also provide evidence for targeted traffic education on proper behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cross-modal work helps OMC improve the safety of commercial transportation

DOT National Transportation Integrated Search

1997-01-01

This article describes the Commercial Vehicle Information System (CVIS), designed to deploy a national safety program for the U.S. commercial trucking fleet. CVIS is built around a safety analysis algorithm called SafeStat which constructs a profile ...

Exploring Typical and Atypical Safety Climate Perceptions of Practitioners in the Repair, Maintenance, Minor Alteration and Addition (RMAA) Sector in Hong Kong.

PubMed

Hon, Carol K H; Liu, Yulin

2016-09-22

The safety of repair, maintenance, minor alteration and addition (RMAA) work is an under-explored area. This study explored the typical and atypical safety climate perceptions of practitioners in the RMAA sector in Hong Kong, based on a self-administered questionnaire survey of 662 local practitioners in the industry. Profile analysis, via multidimensional scaling of the respondents' scores of three safety climate scales, identified one typical perception: high in management commitment to occupational health and safety (OHS) and employee involvement, low in applicability for safety rules and regulations, and low in responsibility for OHS. The respondents were clustered into typical and atypical perception groups according to their safety climate scores' match to the typical perception. A comparison of demographics between the two groups with logistic regression found that work level and direct employer significantly affect their classification. A multivariate analysis of variance of safety performance measures between the two groups indicated that the typical group had a significantly higher level of safety compliance than the atypical group, with no significant difference in safety participation or injury. The significance of this study lies in revealing the typical safety climate perception profile pattern of RMAA works and offering a new perspective of safety climate research.

Exploring Typical and Atypical Safety Climate Perceptions of Practitioners in the Repair, Maintenance, Minor Alteration and Addition (RMAA) Sector in Hong Kong

PubMed Central

Hon, Carol K.H.; Liu, Yulin

2016-01-01

The safety of repair, maintenance, minor alteration and addition (RMAA) work is an under-explored area. This study explored the typical and atypical safety climate perceptions of practitioners in the RMAA sector in Hong Kong, based on a self-administered questionnaire survey of 662 local practitioners in the industry. Profile analysis, via multidimensional scaling of the respondents’ scores of three safety climate scales, identified one typical perception: high in management commitment to occupational health and safety (OHS) and employee involvement, low in applicability for safety rules and regulations, and low in responsibility for OHS. The respondents were clustered into typical and atypical perception groups according to their safety climate scores’ match to the typical perception. A comparison of demographics between the two groups with logistic regression found that work level and direct employer significantly affect their classification. A multivariate analysis of variance of safety performance measures between the two groups indicated that the typical group had a significantly higher level of safety compliance than the atypical group, with no significant difference in safety participation or injury. The significance of this study lies in revealing the typical safety climate perception profile pattern of RMAA works and offering a new perspective of safety climate research. PMID:27669269

Mortality associated with administration of high-dose tranexamic acid and aprotinin in primary open-heart procedures: a retrospective analysis.

PubMed

Sander, Michael; Spies, Claudia D; Martiny, Viktoria; Rosenthal, Christoph; Wernecke, Klaus-Dieter; von Heymann, Christian

2010-01-01

Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding. Because of safety concerns, aprotinin was withdrawn from the market in 2007. Since then, tranexamic acid (TXA) has become the antifibrinolytic treatment of choice in many heart centers. The safety profile of TXA has not been extensively studied. Therefore, the aim of this study was to evaluate safety and efficiency of TXA compared with aprotinin in cardiac surgery. Since July 1, 2006, TXA has been administered at a dose of 50 mg/kg tranexamic acid before cardiopulmonary bypass (CPB) and 50 mg/kg into the priming fluid of the CPB. Prior to this, all patients were treated with aprotinin at a dose of 50,000 KIU per kilogram body weight. Safety was evaluated with mortality, biomarkers, and the diagnosis of myocardial infarction, ischemic stroke, convulsive seizures, and acute renal failure in the intensive care unit (ICU), intermediate care unit (IMCU), and hospital stay. Efficiency was evaluated by the need for transfusion of blood products and total postoperative blood loss. After informed consent, 893 patients were included in our database (557 consecutive patients receiving aprotinin and 336 patients receiving TXA). A subgroup of 320 patients undergoing open-heart procedures (105 receiving TXA and 215 receiving aprotinin) was analyzed separately. In the aprotinin group, a higher rate of late events of ischemic stroke (3.4% versus 0.9%; P = 0.02) and neurologic disability (5.8% versus 2.4%; P = 0.02) was found. The rate of postoperative convulsive seizures was increased in tendency in patients receiving TXA (2.7% versus 0.9%; P = 0.05). The use of TXA was associated with higher cumulative drainage losses (PANOVA < 0.01; Ptime < 0.01) and a higher rate of repeated thoracotomy for bleeding (6.9% versus 2.4%; P < 0.01). In the subgroup of patients with open-chamber procedures, mortality was higher in the TXA group (16.2% TXA versus 7.5% aprotinin; P = 0.02). Multivariate logistic regression identified EURO score II and CPB time as additional risk factors for this increased mortality. The use of high-dose TXA is questioned, as our data suggest an association between higher mortality and minor efficiency while the safety profile of this drug is not consistently improved. Further confirmatory prospective studies evaluating the efficacy and safety profile of TXA are urgently needed to find a safe dosage for this antifibrinolytic drug.

Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile.

PubMed

Kumar, Nagendra; Chaurasia, Sundeep; Patel, Ravi R; Khan, Gayasuddin; Kumar, Vikas; Mishra, Brahmeshwar

2017-03-01

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Safety of vedolizumab in the treatment of Crohn's disease and ulcerative colitis.

PubMed

Hagan, Matilda; Cross, Raymond K

2015-01-01

Vedolizumab is the latest FDA-approved anti-integrin therapy for treatment of moderate-to-severe inflammatory bowel disease (IBD). The safety and efficacy of vedolizumab have been studied in short-term clinical trials. This paper reviews the safety profile of vedolizumab compared with other biologics. It also highlights the mechanism of action of the medication. We discuss the current position of vedolizumab in our current algorithm for IBD management and comment on future prospects of the drug. Vedolizumab appears to be a safe and effective option in the treatment of moderate-to-severe IBD in the short term. Long-term observational studies and post-marketing safety data are needed to ascertain the long-term efficacy and side effect profile.

Safety and efficacy of rivaroxaban compared with warfarin in patients undergoing peripheral arterial procedures.

PubMed

Talukdar, Anjan; Wang, S Keisin; Czosnowski, Lauren; Mokraoui, Nassim; Gupta, Alok; Fajardo, Andres; Dalsing, Michael; Motaganahalli, Raghu

2017-10-01

Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions. This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ 2 test to compare demographics, readmissions because of bleeding, and the need for secondary interventions. Logistic regression models were used for analysis of variables associated with bleeding complications and secondary interventions. The Fisher exact test was used for power analysis. There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban. Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65 years) but an increased risk for secondary interventions. Further studies with a larger cohort are required to validate our results. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

RhIG for the treatment of immune thrombocytopenia: consensus and controversy

PubMed Central

Despotovic, Jenny M.; Lambert, Michele P.; Herman, Jay H.; Gernsheimer, Terry B.; McCrae, Keith R.; Tarantino, Michael D.; Bussel, James B.

2012-01-01

Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection. PMID:21981825

Examining the safety of PPAR agonists - current trends and future prospects.

PubMed

Bortolini, Michele; Wright, Matthew B; Bopst, Martin; Balas, Bogdana

2013-01-01

The peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists, fibrates and glitazones, are effective treatments for dyslipidemia and type 2 diabetes mellitus, respectively, but exhibit class-related, as well as compound-specific safety characteristics. This article reviews the profiles of PPAR-α, PPAR-γ, and dual PPAR-α/γ agonists with regard to class-related and compound-specific efficacy and adverse effects. We explore how learnings from first-generation drugs are being applied to develop safer PPAR-targeted therapies. The finding that rosiglitazone may increase risk for cardiovascular events has led to regulatory guidelines requiring demonstration of cardiovascular safety in appropriate outcome trials for new type 2 diabetes mellitus drugs. The emerging data on the possibly increased risk of bladder cancer with pioglitazone may prompt the need for post-approval safety studies for new drugs. Since PPAR-α and -γ affect key cardiometabolic risk factors (diabetic dyslipidemia, insulin resistance, hyperglycemia, and inflammation) in a complementary fashion, combining their benefits has emerged as a particularly attractive option. New PPAR-targeted therapies that balance the relative potency and/or activity toward PPAR-α and -γ have shown promise in retaining efficacy while reducing potential side effects.

Non-axisymmetric equilibrium reconstruction of a current-carrying stellarator using external magnetic and soft x-ray inversion radius measurements

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

Ma, X., E-mail: xzm0005@auburn.edu; Maurer, D. A.; Knowlton, S. F.

2015-12-15

Non-axisymmetric free-boundary equilibrium reconstructions of stellarator plasmas are performed for discharges in which the magnetic configuration is strongly modified by ohmically driven plasma current. These studies were performed on the compact toroidal hybrid device using the V3FIT reconstruction code with a set of 50 magnetic diagnostics external to the plasma. With the assumption of closed magnetic flux surfaces, the reconstructions using external magnetic measurements allow accurate estimates of the net toroidal flux within the last closed flux surface, the edge safety factor, and the plasma shape of these highly non-axisymmetric plasmas. The inversion radius of standard sawteeth is used tomore » infer the current profile near the magnetic axis; with external magnetic diagnostics alone, the current density profile is imprecisely reconstructed.« less

Non-axisymmetric equilibrium reconstruction of a current-carrying stellarator using external magnetic and soft x-ray inversion radius measurements

NASA Astrophysics Data System (ADS)

Ma, X.; Maurer, D. A.; Knowlton, S. F.; ArchMiller, M. C.; Cianciosa, M. R.; Ennis, D. A.; Hanson, J. D.; Hartwell, G. J.; Hebert, J. D.; Herfindal, J. L.; Pandya, M. D.; Roberds, N. A.; Traverso, P. J.

2015-12-01

Non-axisymmetric free-boundary equilibrium reconstructions of stellarator plasmas are performed for discharges in which the magnetic configuration is strongly modified by ohmically driven plasma current. These studies were performed on the compact toroidal hybrid device using the V3FIT reconstruction code with a set of 50 magnetic diagnostics external to the plasma. With the assumption of closed magnetic flux surfaces, the reconstructions using external magnetic measurements allow accurate estimates of the net toroidal flux within the last closed flux surface, the edge safety factor, and the plasma shape of these highly non-axisymmetric plasmas. The inversion radius of standard sawteeth is used to infer the current profile near the magnetic axis; with external magnetic diagnostics alone, the current density profile is imprecisely reconstructed.

Non-axisymmetric equilibrium reconstruction of a current-carrying stellarator using external magnetic and soft x-ray inversion radius measurements

DOE PAGES

Ma, X.; Maurer, D. A.; Knowlton, Stephen F.; ...

2015-12-22

Non-axisymmetric free-boundary equilibrium reconstructions of stellarator plasmas are performed for discharges in which the magnetic configuration is strongly modified by ohmically driven plasma current. These studies were performed on the compact toroidal hybrid device using the V3FIT reconstruction code with a set of 50 magnetic diagnostics external to the plasma. With the assumption of closed magnetic flux surfaces, the reconstructions using external magnetic measurements allow accurate estimates of the net toroidal flux within the last closed flux surface, the edge safety factor, and the plasma shape of these highly non-axisymmetric plasmas. Lastly, the inversion radius of standard saw-teeth is usedmore » to infer the current profile near the magnetic axis; with external magnetic diagnostics alone, the current density profile is imprecisely reconstructed.« less

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes.

PubMed

Kullenberg, Torbjörn; Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

2016-08-01

Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. ClincialTrials.gov, clinicaltrials.gov, NCT00069329. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Modeling for influenza vaccines and adjuvants profile for safety prediction system using gene expression profiling and statistical tools

PubMed Central

Sasaki, Eita; Momose, Haruka; Hiradate, Yuki; Furuhata, Keiko; Takai, Mamiko; Asanuma, Hideki; Ishii, Ken J.

2018-01-01

Historically, vaccine safety assessments have been conducted by animal testing (e.g., quality control tests and adjuvant development). However, classical evaluation methods do not provide sufficient information to make treatment decisions. We previously identified biomarker genes as novel safety markers. Here, we developed a practical safety assessment system used to evaluate the intramuscular, intraperitoneal, and nasal inoculation routes to provide robust and comprehensive safety data. Influenza vaccines were used as model vaccines. A toxicity reference vaccine (RE) and poly I:C-adjuvanted hemagglutinin split vaccine were used as toxicity controls, while a non-adjuvanted hemagglutinin split vaccine and AddaVax (squalene-based oil-in-water nano-emulsion with a formulation similar to MF59)-adjuvanted hemagglutinin split vaccine were used as safety controls. Body weight changes, number of white blood cells, and lung biomarker gene expression profiles were determined in mice. In addition, vaccines were inoculated into mice by three different administration routes. Logistic regression analyses were carried out to determine the expression changes of each biomarker. The results showed that the regression equations clearly classified each vaccine according to its toxic potential and inoculation amount by biomarker expression levels. Interestingly, lung biomarker expression was nearly equivalent for the various inoculation routes. The results of the present safety evaluation were confirmed by the approximation rate for the toxicity control. This method may contribute to toxicity evaluation such as quality control tests and adjuvant development. PMID:29408882

Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials.

PubMed

Lee, Young Ho; Bae, Sang-Cheol

2016-11-01

This study aimed to assess the relative efficacy and safety of biologics and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate response to tumor necrosis factor (TNF) inhibitors. We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with RA that inadequately responds to TNF inhibitors. Four RCTs including 1796 patients met the inclusion criteria. The tocilizumab 8 mg group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA = 0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415) and placebo (SUCRA = 0). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the treatment options. Tocilizumab 8 mg was the second-line non-TNF biologic with the highest performance regarding an early good response based on ACR20 response rate and acceptable safety profile, followed by rituximab, abatacept and tofacitinib in patients with RA and an inadequate response to anti-TNF therapy, and none of these treatments were associated with a significant risk of withdrawal due to adverse events. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

The Expected Net Present Value of Developing Weight Management Drugs in the Context of Drug Safety Litigation.

PubMed

Chawla, Anita; Carls, Ginger; Deng, Edmund; Tuttle, Edward

2015-07-01

Following withdrawals, failures, and significant litigation settlements, drug product launches in the anti-obesity category slowed despite a large and growing unmet need. Litigation concerns, a more risk-averse regulatory policy, and the difficulty of developing a product with a compelling risk-benefit profile in this category may have limited innovators' expected return on investment and restricted investment in this therapeutic area. The objective of the study was to estimate perceived manufacturer risk associated with product safety litigation and increased development costs vs. revenue expectations on anticipated return on investment and to determine which scenarios might change a manufacturer's investment decision. Expected net present value of a weight-management drug entering pre-clinical trials was calculated for a range of scenarios representing evolving expectations of development costs, revenue, and litigation risk over the past 25 years. These three factors were based on published estimates, historical data, and analogs from other therapeutic areas. The main driver in expected net present value calculations is expected revenue, particularly if one assumes that litigation risk and demand are positively correlated. Changes in development costs associated with increased regulatory concern with potential safety issues for the past 25 years likely did not impact investment decisions. Regulatory policy and litigation risk both played a role in anti-obesity drug development; however, product revenue-reflecting efficacy at acceptable levels of safety-was by far the most important factor. To date, relatively modest sales associated with recent product introductions suggest that developing a product that is sufficiently efficacious with an acceptable level of safety continues to be the primary challenge in this market.

Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism

PubMed Central

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

2016-01-01

The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors’ expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers’ caring and communication (CCC) and coworkers’ role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry. PMID:27834823

Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism.

PubMed

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

2016-11-08

The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors' expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers' caring and communication (CCC) and coworkers' role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry.

Differential Adjustment Among Rural Adolescents Exposed to Family Violence.

PubMed

Sianko, Natallia; Hedge, Jasmine M; McDonell, James R

2016-04-22

This study examines differences in psychological adjustment in a sample of rural adolescents who have been exposed to family violence. Self-report questionnaires were administered to 580 adolescents and their primary caregivers. The results revealed that over two thirds of the study participants (68.8%) had been exposed to violence in their families. As hypothesized, cluster analysis identified several profiles among adolescents, distinguished by their psychological and emotional functioning: well adjusted (46.2%), moderately adjusted (44.3%), and struggling (9.5%). Discriminant function analysis confirmed the groupings and revealed that family functioning was among the most influential factors explaining adjustment differences. Multivariate analyses of variance (MANOVAs) further showed that adolescents from each of the three adjustment profiles reported significantly different levels of family social support, parental involvement, and perceived neighborhood safety. Overall, the results confirm heterogeneity of adolescent adaptation in the aftermath of family violence and provide insights into family and neighborhood factors that account for variability in adolescents' reactions to violence. Implications for future research and practical interventions are discussed. © The Author(s) 2016.

A hierarchical factor analysis of a safety culture survey.

PubMed

Frazier, Christopher B; Ludwig, Timothy D; Whitaker, Brian; Roberts, D Steve

2013-06-01

Recent reviews of safety culture measures have revealed a host of potential factors that could make up a safety culture (Flin, Mearns, O'Connor, & Bryden, 2000; Guldenmund, 2000). However, there is still little consensus regarding what the core factors of safety culture are. The purpose of the current research was to determine the core factors, as well as the structure of those factors that make up a safety culture, and establish which factors add meaningful value by factor analyzing a widely used safety culture survey. A 92-item survey was constructed by subject matter experts and was administered to 25,574 workers across five multi-national organizations in five different industries. Exploratory and hierarchical confirmatory factor analyses were conducted revealing four second-order factors of a Safety Culture consisting of Management Concern, Personal Responsibility for Safety, Peer Support for Safety, and Safety Management Systems. Additionally, a total of 12 first-order factors were found: three on Management Concern, three on Personal Responsibility, two on Peer Support, and four on Safety Management Systems. The resulting safety culture model addresses gaps in the literature by indentifying the core constructs which make up a safety culture. This clarification of the major factors emerging in the measurement of safety cultures should impact the industry through a more accurate description, measurement, and tracking of safety cultures to reduce loss due to injury. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Targeted therapies in non-small cell lung carcinoma: what have we achieved so far?

PubMed Central

Houhou, Wissam

2013-01-01

The search for innovative therapeutic agents in non-small cell lung cancer (NSCLC) has witnessed a swift evolution. The number of targeted drugs that can improve patient outcomes with an acceptable safety profile is steadily increasing. In this review, we highlight current drugs that have already been approved or are under evaluation for the treatment of patients with NSCLC, either in monotherapy or combined therapy for both the first- and second-line settings. Experience with drugs targeting the vascular endothelial growth factor and its receptor, as well as the epidermal growth factor receptor is summarized. Moreover, we provide an overview of more novel targets in NSCLC and initial experience with the respective therapeutic agents. PMID:23858333

Safety and tolerability of new-generation anti-obesity medications: a narrative review.

PubMed

Patel, Dhiren K; Stanford, Fatima Cody

2018-03-01

The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk-benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk-benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk-benefit.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Electron critical gradient scale length measurements of ICRF heated L-mode plasmas at Alcator C-Mod tokamak

NASA Astrophysics Data System (ADS)

Houshmandyar, S.; Hatch, D. R.; Horton, C. W.; Liao, K. T.; Phillips, P. E.; Rowan, W. L.; Zhao, B.; Cao, N. M.; Ernst, D. R.; Greenwald, M.; Howard, N. T.; Hubbard, A. E.; Hughes, J. W.; Rice, J. E.

2018-04-01

A profile for the critical gradient scale length (Lc) has been measured in L-mode discharges at the Alcator C-Mod tokamak, where electrons were heated by an ion cyclotron range of frequency through minority heating with the intention of simultaneously varying the heat flux and changing the local gradient. The electron temperature gradient scale length (LTe-1 = |∇Te|/Te) profile was measured via the BT-jog technique [Houshmandyar et al., Rev. Sci. Instrum. 87, 11E101 (2016)] and it was compared with electron heat flux from power balance (TRANSP) analysis. The Te profiles were found to be very stiff and already above the critical values, however, the stiffness was found to be reduced near the q = 3/2 surface. The measured Lc profile is in agreement with electron temperature gradient (ETG) models which predict the dependence of Lc-1 on local Zeff, Te/Ti, and the ratio of the magnetic shear to the safety factor. The results from linear Gene gyrokinetic simulations suggest ETG to be the dominant mode of turbulence in the electron scale (k⊥ρs > 1), and ion temperature gradient/trapped electron mode modes in the ion scale (k⊥ρs < 1). The measured Lc profile is in agreement with the profile of ETG critical gradients deduced from Gene simulations.

Dual Inhibition of the Epidermal Growth Factor Receptor Pathway with Cetuximab and Erlotinib: A Phase I Study in Patients with Advanced Solid Malignancies

PubMed Central

Guarino, Michael J.; Schneider, Charles J.; Hosford, Martha A.; Brahmer, Julie R.; Rudin, Charles M.; Finckenstein, Friedrich Graf; Philip-Norton, Robyn E.; Lu, Haolan; Weber, Martin R.; Ettinger, David S.

2017-01-01

Purpose To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies. Patients and Methods Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m2 i.v. weekly) in combination with a fixed dose of erlotinib (150 mg daily orally) until disease progression or unacceptable toxicity. Results Twenty-two patients were treated, including 14 patients (64%) with non-small cell lung cancer. Twenty patients received combination treatment at the highest dose level for a median of 5.5 weeks (range, 1–31 weeks). One dose-limiting toxicity was observed: grade 3 skin rash. Overall, the most common adverse events (any grade, grade 3/4) were consistent with the safety profiles of the individual drugs: acneform rash (100%, 9%), diarrhea (77%, 5%), and hypomagnesemia (59%, 12%). Seven of 18 evaluable patients (38.9%) had stable disease lasting for a median of 16.6 weeks (range, 6.1–25.1 weeks). Conclusion Dual EGFR inhibition with cetuximab and erlotinib is feasible; the observed toxicities were manageable and consistent with the safety profiles of the individual drugs. The recommended doses for phase II studies are 250 mg/m2 i.v. weekly for cetuximab and 150 mg daily orally for erlotinib. PMID:19182243

Environmental Assessment: T-6 Aircraft Basing and Operation

DTIC Science & Technology

2004-06-01

The operating characteristics of the T -6 are similar to the T-37. Thus, the T-6 traffic pattern aircraft ground tracks, profiles , and airspeeds are...low-income populations.” Adverse is defined by the Federal Interagency Working Group on Environmental Justice as “having a deleterious effect on...types of aircraft (i.e., large and trainer) was considered a significant safety issue. Safety concerns include mixing the flight profiles of two

Determination of current and rotational transform profiles in a current-carrying stellarator using soft x-ray emissivity measurements

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

Ma, X.; Cianciosa, M. R.; Ennis, D. A.

In this research, collimated soft X-ray (SXR) emissivity measurements from multi-channel cameras on the Compact Toroidal Hybrid (CTH) tokamak/torsatron device are incorporated in the 3D equilibrium reconstruction code V3FIT to reconstruct the shape of flux surfaces and infer the current distribution within the plasma. Equilibrium reconstructions of sawtoothing plasmas that use data from both SXR and external magnetic diagnostics show the central safety factor to be near unity under the assumption that SXR iso-emissivity contours lie on magnetic flux surfaces. The reconstruction results are consistent with those using the external magnetic data and a constraint on the location of qmore » = 1 surfaces determined from the sawtooth inversion surface extracted from SXR brightness profiles. The agreement justifies the use of approximating SXR emission as a flux function in CTH, at least within the core of the plasma, subject to the spatial resolution of the SXR diagnostics. Lastly, this improved reconstruction of the central current density indicates that the current profile peakedness decreases with increasing external transform and that the internal inductance is not a relevant measure of how peaked the current profile is in hybrid discharges.« less

A Mapping Model for Magnetic Fields with q-profile Variations Typical of Internal Transport Barrier Experiments

NASA Astrophysics Data System (ADS)

Rapoport, B. I.; Pavlenko, I.; Weyssow, B.; Carati, D.

2002-11-01

Recent studies of ion and electron transport indicate that the safety factor profile, q(r), affects internal transport barrier (ITB) formation in magnetic confinement devices [1, 2]. These studies are consistent with experimental observations that low shear suppresses magnetic island interaction and associated stochasticity when the ITB is formed [3]. In this sense the position and quality of the ITB depend on the stochasticity of the magnetic field, and can be controlled by q(r). This study explores effects of the q-profile on magnetic field stochasticity using two-dimensional mapping techniques. Q-profiles typical of ITB experiments are incorporated into Hamiltonian maps to investigate the relation between magnetic field stochasticity and ITB parameters predicted by other models. It is shown that the mapping technique generates results consistent with these predictions, and suggested that Hamiltonian mappings can be useful as simple and computationally inexpensive approximation methods for describing the magnetic field in ITB experiments. 1. I. Voitsekhovitch et al. 29th EPS Conference on Plasma Physics and Controlled Fusion (2002). O-4.04. 2. G.M.D. Hogeweij et al. Nucl. Fusion. 38 (1998): 1881. 3. K.A. Razumova et al. Plasma Phys. Contr. Fusion. 42 (2000): 973.

Determination of current and rotational transform profiles in a current-carrying stellarator using soft x-ray emissivity measurements

NASA Astrophysics Data System (ADS)

Ma, X.; Cianciosa, M. R.; Ennis, D. A.; Hanson, J. D.; Hartwell, G. J.; Herfindal, J. L.; Howell, E. C.; Knowlton, S. F.; Maurer, D. A.; Traverso, P. J.

2018-01-01

Collimated soft X-ray (SXR) emissivity measurements from multi-channel cameras on the Compact Toroidal Hybrid (CTH) tokamak/torsatron device are incorporated in the 3D equilibrium reconstruction code V3FIT to reconstruct the shape of flux surfaces and infer the current distribution within the plasma. Equilibrium reconstructions of sawtoothing plasmas that use data from both SXR and external magnetic diagnostics show the central safety factor to be near unity under the assumption that SXR iso-emissivity contours lie on magnetic flux surfaces. The reconstruction results are consistent with those using the external magnetic data and a constraint on the location of q = 1 surfaces determined from the sawtooth inversion surface extracted from SXR brightness profiles. The agreement justifies the use of approximating SXR emission as a flux function in CTH, at least within the core of the plasma, subject to the spatial resolution of the SXR diagnostics. This improved reconstruction of the central current density indicates that the current profile peakedness decreases with increasing external transform and that the internal inductance is not a relevant measure of how peaked the current profile is in hybrid discharges.

Determination of current and rotational transform profiles in a current-carrying stellarator using soft x-ray emissivity measurements

DOE PAGES

Ma, X.; Cianciosa, M. R.; Ennis, D. A.; ...

2018-01-31

In this research, collimated soft X-ray (SXR) emissivity measurements from multi-channel cameras on the Compact Toroidal Hybrid (CTH) tokamak/torsatron device are incorporated in the 3D equilibrium reconstruction code V3FIT to reconstruct the shape of flux surfaces and infer the current distribution within the plasma. Equilibrium reconstructions of sawtoothing plasmas that use data from both SXR and external magnetic diagnostics show the central safety factor to be near unity under the assumption that SXR iso-emissivity contours lie on magnetic flux surfaces. The reconstruction results are consistent with those using the external magnetic data and a constraint on the location of qmore » = 1 surfaces determined from the sawtooth inversion surface extracted from SXR brightness profiles. The agreement justifies the use of approximating SXR emission as a flux function in CTH, at least within the core of the plasma, subject to the spatial resolution of the SXR diagnostics. Lastly, this improved reconstruction of the central current density indicates that the current profile peakedness decreases with increasing external transform and that the internal inductance is not a relevant measure of how peaked the current profile is in hybrid discharges.« less

Efficacy and safety of two doses of Norditropin® (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients.

PubMed

Ozono, Keiichi; Ogata, Tsutomu; Horikawa, Reiko; Matsubara, Yoichi; Ogawa, Yoshihisa; Nishijima, Keiji; Yokoya, Susumu

2018-02-26

This randomized double-blind multicenter trial (NCT01927861) evaluated the growth-promoting effect and safety of Norditropin ® (NN220; somatropin) in Japanese children with short stature due to Noonan syndrome. Prepubertal children aged 3-<11 years (boys) or 3-<10 years (girls) with Noonan syndrome were randomized to receive GH 0.033 mg/kg/day (n = 25, mean age 6.57 years, 11 females) or 0.066 mg/kg/day (n = 26, mean age 6.06 years, eight females) for 104 weeks. Change in height standard deviation score (HSDS) from baseline was analyzed based on an ANCOVA model. Baseline HSDS was -3.24. Estimated change in HSDS [95% CI] after 104 weeks' treatment was 0.84 [0.66, 1.02] and 1.47 [1.29, 1.64] for the lower and higher doses, respectively; estimated mean difference 0.63 [0.38, 0.88], p < 0.0001. Rates and patterns of adverse events (AEs) were similar between groups. Most were mild and reported as unlikely to be related to Norditropin ® . There were no withdrawals due to AEs. Insulin-like growth factor-I SDS increased from -1.71 to -0.64 (0.033 mg/kg/day) and to 0.63 (0.066 mg/kg/day). HbA 1c increased slightly (0.033 mg/kg/day: +0.14%; 0.066 mg/kg/day: +0.13%); glucose profiles were almost unchanged; insulin profiles increased in both groups in the oral glucose tolerance test. There were no clinically significant abnormal electrocardiogram or echocardiography findings. We conclude that Norditropin ® at doses of 0.033 mg/kg/day or 0.066 mg/kg/day for 104 weeks increases height in Japanese children with short stature due to Noonan syndrome, with a favorable safety profile. The effect was greater with 0.066 mg/kg/day compared with 0.033 mg/kg/day.

Nonbibliographic Databases in a Corporate Health, Safety, and Environment Organization.

ERIC Educational Resources Information Center

Cubillas, Mary M.

1981-01-01

Summarizes the characteristics of TOXIN, CHEMFILE, and the Product Profile Information System (PPIS), nonbibliographic databases used by Shell Oil Company's Health, Safety, and Environment Organization. (FM)

New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim.

PubMed

Ghidini, Michele; Hahne, Jens Claus; Trevisani, Francesco; Panni, Stefano; Ratti, Margherita; Toppo, Laura; Tomasello, Gianluca

2016-01-01

Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2) and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim's efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the currently available literature data on balugrastim.

Safety of anti-tumor necrosis factor therapy during pregnancy in patients with inflammatory bowel disease.

PubMed

Androulakis, Ioannis; Zavos, Christos; Christopoulos, Panagiotis; Mastorakos, George; Gazouli, Maria

2015-12-21

Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor (TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that anti-TNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of anti-TNF therapeutic agents on pregnancy outcomes.

Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

PubMed

Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

2016-01-01

Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Evaluation of safety and efficacy of a fixed olmesartan/amlodipine combination therapy compared to single monotherapies.

PubMed

Derosa, Giuseppe; Cicero, Arrigo Francesco Giuseppe; Carbone, Anna; Querci, Fabrizio; Fogari, Elena; D'Angelo, Angela; Maffioli, Pamela

2013-09-01

Hypertension is known to be one of the main risk factors for cardiovascular disease. To evaluate the safety and efficacy of a fixed olmesartan/amlodipine (Olme/Amlo) combination in improving blood pressure control, lipid profile, insulin sensitivity and some inflammatory and insulin resistance markers. Two hundred and seventy-six hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or a single pill containing an Olme/Amlo combination 20/5 mg for 12 months. We evaluated after 6 and 12 months: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, vaspin, visfatin, interleukins 8 and 10 (IL-8 and IL-10, respectively). Patients also underwent an euglycemic, hyperinsulinemic clamp. Olme/Amlo combination was more effective in decreasing SBP, and DPB compared to single monotherapies after 12 months. Olme/Amlo combination, but not amlodipine, decreased FPG after 12 months. FPI and HOMA index were decreased, and M value increased by Olme/Amlo combination compared to olmesartan monotherapy, and to amlodipine monotherapy. Olme/Amlo significantly decreased IL-8 and IL-10 better than each monotherapy. Olme/Amlo single pill combination can be a safe and effective option to reduce blood pressure, improve insulin sensitivity and decrease inflammatory markers.

Attention-deficit hyperactivity disorder medication use: factors involved in prescribing, safety aspects and outcomes.

PubMed

Martinez-Raga, Jose; Ferreros, Amparo; Knecht, Carlos; de Alvaro, Raquel; Carabal, Eloisa

2017-03-01

While treatment of patients with attention-deficit hyperactivity disorder (ADHD) is based on a multimodal approach that combines medication with specific psychological interventions, pharmacotherapy alone is generally considered an essential and cost-effective element. This paper aims to comprehensively and critically review factors involved in prescribing and medication use in individuals diagnosed with ADHD, focusing on the difficulties facing patients with ADHD seeking treatment, as well as the safety and tolerability aspects of ADHD pharmacotherapies, with particular attention on the cardiovascular adverse events and the potential risk of misuse or diversion of ADHD medications. A comprehensive and systematic literature search of PubMed/MEDLINE database was conducted to identify studies published in peer-reviewed journals until 1 August 2016. Children, adolescents and adults often encounter significant difficulties in the process of accessing specialist assessment and treatment for ADHD as a consequence of disparities in service organization and available treatment provision. Despite the well-established efficacy and overall safety profile, ADHD medications are not exempt from adverse events. The cardiovascular safety of pharmacotherapies used for treating individuals with ADHD has raised particular concerns; however there is little evidence of serious cardiovascular adverse events, including no serious corrected QT (QTc) abnormalities associated with stimulants, atomoxetine or α2-adrenergic receptor agonists. Although the abuse of prescription stimulant drugs, particularly, short-acting stimulants is a prevalent and growing problem, nonmedical use of prescription stimulants within the clinical context is very limited. In addition, nonstimulant ADHD medications lack any reinforcing effects and consequently any abuse potential.

Educating the ambulance technician, paramedic, and clinical supervisor: using factor analysis to inform the curriculum

PubMed Central

Kilner, T

2004-01-01

Methods: Data generated by a Delphi study investigating the desirable attributes of ambulance technician, paramedic, and clinical supervisor were subject to factor analysis to explore inter-relations between the variables or desirable attributes. Variables that loaded onto any factor at a correlation level of >0.3 were included in the analysis. Results: Three factors emerged in each of the occupational groups. In respect of the ambulance technician these factors may be described as; core professional skills, individual and collaborative approaches to health and safety, and the management of self and clinical situations. For the paramedic the themes are; core professional skills, management of self and clinical situations, and approaches to health and safety. For the clinical supervisor there is again a theme described as core professional skills, with a further two themes described as role model and lifelong learning. Conclusions: The profile of desirable attributes emerging from this study are remarkably similar to the generic benchmark statements for health care programmes outlined by the Quality Assurance Agency for Higher Education. It seems that a case is emerging for a revision of the curriculum currently used for the education and training of ambulance staff, which is more suited to a consumer led health service and which reflects the broader professional base seen in programmes associated with other healthcare professions. This study has suggested outline content, and module structure for the education of the technician, paramedic, and clinical supervisor, based on empirical evidence. PMID:15107389

Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

PubMed

Montalescot, Gilles; Walenga, Jeanine M

2009-01-01

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Safety Profile of Cough and Cold Medication Use in Pediatrics.

PubMed

Green, Jody L; Wang, George Sam; Reynolds, Kate M; Banner, William; Bond, G Randall; Kauffman, Ralph E; Palmer, Robert B; Paul, Ian M; Dart, Richard C

2017-06-01

The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program. Cases with adverse events (AEs) after ingestion of at least 1 index CCM ingredient (brompheniramine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, and pseudoephedrine) in children <12 years of age were collected from 5 data sources. An expert panel determined relatedness, dose, intent, and risk factors. Case characteristics and AEs are described. Of the 4202 cases reviewed, 3251 (77.4%) were determined to be at least potentially related to a CCM, with accidental unsupervised ingestions (67.1%) and medication errors (13.0%) the most common exposure types. Liquid (67.3%), pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children <2 years of age (70.0%) and none involved a therapeutic dose. The overall reported AE rate was 0.573 cases per 1 million units (ie, tablets, gelatin capsules, or liquid equivalent) sold (95% confidence interval, 0.553-0.593) or 1 case per 1.75 million units. The rate of AEs associated with CCMs in children was low. Fatalities occurred even less frequently. No fatality involved a therapeutic dose. Accidental unsupervised ingestions were the most common exposure types and single-ingredient, pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts. Copyright © 2017 by the American Academy of Pediatrics.

The role of ferric carboxymaltose in the treatment of iron deficiency anemia in patients with gastrointestinal disease.

PubMed

Koduru, Pramoda; Abraham, Bincy P

2016-01-01

Iron deficiency anemia (IDA) is the most common form of nutritional anemia worldwide. Iron plays a pivotal role in vital functioning of almost every organ system. IDA affects both physical and psychological functioning of humans. Oral iron is considered as first-line therapy for the treatment of IDA due to low cost, good safety profile and ease of administration. However, the absorption of oral iron is affected by several factors and incidence of gastrointestinal side effects can lead to lack of adherence to therapy as well as poor efficacy. This has led to the emergence of intravenous iron therapy which is clearly superior to oral iron with higher increment of hemoglobin levels and rapid replenishment of iron stores. Ferric carboxymaltose (FCM) is a novel non-dextran intravenous iron form which has been approved for use in patients with iron deficiency who have had inadequate response to oral iron therapy, intolerance to oral iron, or nondialysis-dependent chronic kidney disease. The safety and efficacy of using FCM for the treatment of IDA has been demonstrated in several clinical trials. One dose can provide a large amount of iron and has a very short infusion time. It should be considered as first-line therapy in patients with active inflammation like inflammatory bowel disease when gastrointestinal absorption of oral iron may be compromised. It should also be given to patients who have inadequate response to oral iron therapy. It has been shown to be noninferior to other intravenous iron formulations with a good safety profile and produced fewer anaphylactic reactions.

Cardiovascular risk-benefit profile of sibutramine.

PubMed

Scheen, A J

2010-01-01

Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of these complex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular outcomes might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT (Sibutramine Cardiovascular and Diabetes Outcome Study) was designed to prospectively evaluate the efficacy/safety ratio of sibutramine in a high-risk population. The efficacy/safety results of the first 6-week lead-in open period of treatment with sibutramine 10 mg/day were reassuring in 10 742 overweight/obese high-risk subjects (97% had cardiovascular disease, 88% had hypertension, and 84% had type 2 diabetes mellitus). However, the final results of SCOUT showed that long-term (5 years') treatment with sibutramine (10-15 mg/day) exposed subjects with pre-existing cardiovascular disease to a significantly increased risk for nonfatal myocardial infarction and nonfatal stroke, but not cardiovascular death or all-cause mortality. Because the benefit of sibutramine as a weight-loss aid seems not to outweigh the cardiovascular risks, the European Medicines Agency recommended the suspension of marketing authorizations for sibutramine across the EU. The US FDA stated that the drug should carry a 'black box' warning due to an increased risk of stroke and heart attack in patients with a history of cardiovascular disease. In conclusion, concern still persists about the safety profile of sibutramine regarding cardiovascular outcomes, and the drug should not be prescribed for overweight/obese patients with a high cardiovascular risk profile.

Multiple Sclerosis: Epidemiologic, Clinical, and Therapeutic Aspects.

PubMed

Vidal-Jordana, Angela; Montalban, Xavier

2017-05-01

Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system that affects young people. MS develops in genetically susceptible individuals exposed to different unknown triggering factors. Different phenotypes are described. About 15% of patients present with a primary progressive course and 85% with a relapsing-remitting course. An increasing number of disease-modifying treatments has emerged. Although encouraging, the number of drugs challenges the neurologist because each treatment has its own risk-benefit profile. Patients should be involved in the decision-making process to ensure good treatment and safety monitoring adherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Motor carrier industry profile study : financial and operating performance profiles by industry segment, 2001-2002.

DOT National Transportation Integrated Search

2004-09-01

This report profiles the motor carrier industry and its significant operating segments. It is one of a series of reports analyzing various aspects of the motor carrier industry. Other reports in the series focus on the safety performance of the indus...

Magnetic flux pumping in 3D nonlinear magnetohydrodynamic simulations

NASA Astrophysics Data System (ADS)

Krebs, I.; Jardin, S. C.; Günter, S.; Lackner, K.; Hoelzl, M.; Strumberger, E.; Ferraro, N.

2017-10-01

A self-regulating magnetic flux pumping mechanism in tokamaks that maintains the core safety factor at q ≈1 , thus preventing sawteeth, is analyzed in nonlinear 3D magnetohydrodynamic simulations using the M3D-C1 code. In these simulations, the most important mechanism responsible for the flux pumping is that a saturated (m =1 ,n =1 ) quasi-interchange instability generates an effective negative loop voltage in the plasma center via a dynamo effect. It is shown that sawtoothing is prevented in the simulations if β is sufficiently high to provide the necessary drive for the (m =1 ,n =1 ) instability that generates the dynamo loop voltage. The necessary amount of dynamo loop voltage is determined by the tendency of the current density profile to centrally peak which, in our simulations, is controlled by the peakedness of the applied heat source profile.

Influence of ICRF heating on the stability of TAEs

NASA Astrophysics Data System (ADS)

Sears, J.; Burke, W.; Parker, R. R.; Snipes, J. A.; Wolfe, S.

2007-11-01

Unstable toroidicity-induced Alfv'en eigenmodes (TAEs) can appear spontaneously due to resonant interaction with fast particles such as fusion alphas, raising concern that TAEs may threaten ITER performance. This work investigates the progression of stable TAE damping rates toward instability during a scan of ICRF heating power up to 3.1 MW. Stable eigenmodes are identified in Alcator C-Mod by the Active MHD diagnostic. Unstable TAEs are observed to appear spontaneously in C-Mod limited L-mode plasmas at sufficient tail energies generated by >3 MW of ICRF heating. However preliminary analysis of experiments with moderate ICRF heating power show that TAE stability may not simply degrade with overall fast particle content. There are hints that the stability of some TAEs may be enhanced in the presence of fast particle distribution tails. Furthermore, the radial profile of the energetic particle distribution relative to the safety factor profile affects the ICRF power influence on TAE stability.

Magnetic flux pumping in 3D nonlinear magnetohydrodynamic simulations

DOE PAGES

Krebs, I.; Jardin, S. C.; Gunter, S.; ...

2017-09-27

A self-regulating magnetic flux pumping mechanism in tokamaks that maintains the core safety factor at q≈1, thus preventing sawteeth, is analyzed in nonlinear 3D magnetohydrodynamic simulations using the M3D-C1 code. In these simulations, the most important mechanism responsible for the flux pumping is that a saturated (m=1,n=1) quasi-interchange instability generates an effective negative loop voltage in the plasma center via a dynamo effect. It is shown that sawtoothing is prevented in the simulations if β is sufficiently high to provide the necessary drive for the (m=1,n=1) instability that generates the dynamo loop voltage. In conclusion, the necessary amount of dynamomore » loop voltage is determined by the tendency of the current density profile to centrally peak which, in our simulations, is controlled by the peakedness of the applied heat source profile.« less

Patient Safety Culture in Mutual Insurance Companies in Spain.

PubMed

Manzanera, Rafael; Mira, José Joaquín; Plana, Manel; Moya, Daniel; Guilabert, Mercedes; Ortner, Jordi

2017-02-22

The aim of the study was to assess the safety culture in a mutual insurance sector, searching for improvement opportunities. This sector offers health insurance for work-related injuries and occupational illnesses and represents an annual volume of patients corresponding to approximately 10% of the working population in Europe. A cross-sectional study was conducted to assess the safety culture in the mutual insurance sector in Spain. All physicians, nurses, and physiotherapists (N = 816) working in the organization in hospitals, outpatient clinics, and managerial settings were invited to reply to an online survey. A total of 499 professionals completed the questionnaire (response rate, 61%). Two dimensions were assessed: attitudinal (5 items) and instrumental (5 items). There were no differences between professional profiles or centers in the attitudinal (7.8; standard deviation, 1.3; 95% confidence interval, 7.6-7.9) or instrumental (8.5; standard deviation, 1.0; 95% confidence interval, 8.5-8.6) factors. The lowest level of implementation (<9 points) was related to the following: open disclosure after an adverse event (73%), having a quality and safety plan (75%), prioritizing the improvement of patient care (75%), and involving patients when making decisions on potential treatments (63%). Managers showed lower scores than the rest of professionals' groups (P < 0.05). This intent is to introduce a patient safety culture assessment in the mutual insurance companies. These results may encourage the implementation of quality and safety plans in this sector by paying more attention to attitudinal aspects.

Construction fatality due to electrical contact in Ontario, Canada, 1997-2007.

PubMed

Kim, Hwan; Lewko, John; Garritano, Enzo; Sharma, Bhanu; Moody, Joel; Colantonio, Angela

2016-06-27

Electrical contact is a leading cause of occupational fatality in the construction industry. However, research on the factors that contribute to electricity-related fatality in construction is limited. To characterize, using an adapted Haddon's Matrix, the factors that contribute to electricity-related occupational fatalities in the construction industry in Ontario, Canada. Coroner's data on occupational electricity-related fatalities between 1997-2007 in the construction industry were acquired from the Ontario Ministry of Labour. Using an adapted Haddon's Matrix, we characterized worker, agent, and environmental characteristics of electricity-related occupational fatalities in the province through a narrative text analysis. Electrical contact was responsible for 15% of all occupational fatalities among construction workers in Ontario. Factors associated with said occupational fatalities included direct contact with electrical sources, lower voltage sources, and working outdoors. This study provides a profile of electricity-related occupational fatalities among construction workers in Ontario, and can be used to inform safety regulations.

Evaluation and Synthesis of Polar Aryl- and Heteroaryl Spiroazetidine-Piperidine Acetamides as Ghrelin Inverse Agonists

PubMed Central

2014-01-01

Several polar heteroaromatic acetic acids and their piperidine amides were synthesized and evaluated as ghrelin or type 1a growth hormone secretagogue receptor (GHS-R1a) inverse agonists. Efforts to improve pharmacokinetic and safety profile was achieved by modulating physicochemical properties and, more specifically, emphasizing increased polarity of our chemical series. ortho-Carboxamide containing compounds provided optimal physicochemical, pharmacologic, and safety profile. pH-dependent chemical stability was also assessed with our series. PMID:25699143

A review of inherent safety characteristics of metal alloy sodium-cooled fast reactor fuel against postulated accidents

DOE PAGES

Sofu, Tanju

2015-04-01

The thermal, mechanical, and neutronic performance of the metal alloy fast reactor fuel design complements the safety advantages of the liquid metal cooling and the pool-type primary system. Together, these features provide large safety margins in both normal operating modes and for a wide range of postulated accidents. In particular, they maximize the measures of safety associated with inherent reactor response to unprotected, double-fault accidents, and to minimize risk to the public and plant investment. High thermal conductivity and high gap conductance play the most significant role in safety advantages of the metallic fuel, resulting in a flatter radial temperaturemore » profile within the pin and much lower normal operation and transient temperatures in comparison to oxide fuel. Despite the big difference in melting point, both oxide and metal fuels have a relatively similar margin to melting during postulated accidents. When the metal fuel cladding fails, it typically occurs below the coolant boiling point and the damaged fuel pins remain coolable. Metal fuel is compatible with sodium coolant, eliminating the potential of energetic fuel--coolant reactions and flow blockages. All these, and the low retained heat leading to a longer grace period for operator action, are significant contributing factors to the inherently benign response of metallic fuel to postulated accidents. This paper summarizes the past analytical and experimental results obtained in past sodium-cooled fast reactor safety programs in the United States, and presents an overview of fuel safety performance as observed in laboratory and in-pile tests.« less

A review of inherent safety characteristics of metal alloy sodium-cooled fast reactor fuel against postulated accidents

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

Sofu, Tanju

2015-04-01

The thermal, mechanical, and neutronic performance of the metal alloy fast reactor fuel design complements the safety advantages of the liquid metal cooling and the pool-type primary system. Together, these features provide large safety margins in both normal operating modes and for a wide range of postulated accidents. In particular, they maximize the measures of safety associated with inherent reactor response to unprotected, double-fault accidents, and to minimize risk to the public and plant investment. High thermal conductivity and high gap conductance play the most significant role in safety advantages of the metallic fuel, resulting in a flatter radial temperaturemore » profile within the pin and much lower normal operation and transient temperatures in comparison to oxide fuel. Despite the big difference in melting point, both oxide and metal fuels have a relatively similar margin to melting during postulated accidents. When the metal fuel cladding fails, it typically occurs below the coolant boiling point and the damaged fuel pins remain cool-able. Metal fuel is compatible with sodium coolant, eliminating the potential of energetic fuel coolant reactions and flow blockages. All these, and the low retained heat leading to a longer grace period for operator action, are significant contributing factors to the inherently benign response of metallic fuel to postulated accidents. This paper summarizes the past analytical and experimental results obtained in past sodium-cooled fast reactor safety programs in the United States, and presents an overview of fuel safety performance as observed in laboratory and in-pile tests.« less

Sun safety knowledge and practice in UK postal delivery workers.

PubMed

Houdmont, J; Davis, S; Griffiths, A

2016-06-01

Postal delivery workers spend a large proportion of their work time outdoors, placing them at increased risk of skin cancer. To date, no studies have examined occupational sun safety knowledge and practice within this group in the UK. To describe the occupational sun safety knowledge and practice of UK postal delivery workers and to investigate the association of demographic, personal and occupational factors with knowledge and practice in order to identify potential strategies for improving sun safety in this occupational group. Postal delivery workers completed a questionnaire that collected data on occupational sun safety knowledge and practice in addition to demographic, personal and workplace characteristics. One-way analysis of variances were applied to assess differences in knowledge and practice by these characteristics. A total of 1153 postal delivery workers completed the questionnaire, a 60% response rate. Thirty-three per cent reported receiving sun safety training within the previous 12 months. The majority of respondents reported correct knowledge on three of the six domains and good practice on four of the six behavioural domains. However, only one-fifth of respondents reported wearing sunglasses and ensuring a plentiful intake of water. Knowledge and practice differed significantly according to demographic, personal and workplace characteristics. There is a need to raise the profile of occupational skin cancer in this occupational group and to increase the priority given to occupational sun safety policies alongside targeted and tailored interventions, the effect of which can be evaluated. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine.

Safety assessment of adjuvanted vaccines: Methodological considerations

PubMed Central

Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

2015-01-01

Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

PubMed

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-12-01

Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS ® software. The PROSPERO registration number was CRD42016032606. Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Open-label safety assessment of bilastine in elderly patients with allergic rhinoconjunctivitis and/or urticaria.

PubMed

Sologuren, Ander; Vinas, Rosa; Cordon, Esther; Riesgo, Susana E; Del Mar Fores, Maria; Senan, Maria Rosa; Fernandez, Sonia; Labeaga, Luis; Ruiz-Mijan, Manuel

2018-03-20

Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safetyprofile of bilastine 20 mg in patients aged greater than or equal to 65 years with allergic rhinoconjunctivitis and/or urticaria. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. Theincidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88(95% CI, 0.688 -1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95%CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003- 0.048) and0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged greater than or equal to 65 years.The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma.

PubMed

Woodcock, Ashley; Bakerly, Nawar Diar; New, John P; Gibson, J Martin; Wu, Wei; Vestbo, Jørgen; Leather, David

2015-12-10

Novel therapies need to be evaluated in normal clinical practice to allow a true representation of the treatment effectiveness in real-world settings. The Salford Lung Study is a pragmatic randomised controlled trial in adult asthma, evaluating the clinical effectiveness and safety of once-daily fluticasone furoate (100 μg or 200 μg)/vilanterol 25 μg in a novel dry-powder inhaler, versus existing asthma maintenance therapy. The study was initiated before this investigational treatment was licensed and conducted in real-world clinical practice to consider adherence, co-morbidities, polypharmacy, and real-world factors. Asthma Control Test at week 24; safety endpoints include the incidence of serious pneumonias. The study utilises the Salford electronic medical record, which allows near to real-time collection and monitoring of safety data. The Salford Lung Study is the world's first pragmatic randomised controlled trial of a pre-licensed medication in asthma. Use of patients' linked electronic health records to collect clinical endpoints offers minimal disruption to patients and investigators, and also ensures patient safety. This highly innovative study will complement standard double-blind randomised controlled trials in order to improve our understanding of the risk/benefit profile of fluticasone furoate/vilanterol in patients with asthma in real-world settings. Clinicaltrials.gov, NCT01706198; 04 October 2012.

Clinician perceptions of personal safety and confidence to manage inpatient aggression in a forensic psychiatric setting.

PubMed

Martin, T; Daffern, M

2006-02-01

Inpatient mental health clinicians need to feel safe in the workplace. They also require confidence in their ability to work with aggressive patients, allowing the provision of therapeutic care while protecting themselves and other patients from psychological and physical harm. The authors initiated this study with the predetermined belief that a comprehensive and integrated organizational approach to inpatient aggression was required to support clinicians and that this approach increased confidence and staff perceptions of personal safety. To assess perceptions of personal safety and confidence, clinicians in a forensic psychiatric hospital were surveyed using an adapted version of the Confidence in Coping With Patient Aggression Instrument. In this study clinicians reported the hospital as safe. They reported confidence in their work with aggressive patients. The factors that most impacted on clinicians' confidence to manage aggression were colleagues' knowledge, experience and skill, management of aggression training, use of prevention and intervention strategies, teamwork and the staff profile. These results are considered with reference to an expanding literature on inpatient aggression. It is concluded that organizational resources, policies and frameworks support clinician perceptions of safety and confidence to manage inpatient aggression. However, how these are valued by clinicians and translated into practice at unit level needs ongoing attention.

The safety of vedolizumab for the treatment of ulcerative colitis.

PubMed

Novak, Gregor; Hindryckx, Pieter; Khanna, Reena; Jairath, Vipul; Feagan, Brian G

2017-04-01

Vedolizumab is a humanized monoclonal antibody to the α4β7-integrin that blocks lymphocyte trafficking to the gut and is approved for treatment of patients with moderate-to-severe ulcerative colitis (UC). The gut-selective mechanism of action has the potential to improve vedolizumab's safety profile compared to other approved biologic drugs. Areas covered: We review the mechanism of action, efficacy and safety of vedolizumab treatment for UC. The positioning of vedolizumab in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of vedolizumab restricts immunosuppressive effects to the gut. Vedolizumab is efficacious as induction and maintenance therapy in UC patients who are naïve or refractory to tumor necrosis factor antagonists. No clinically important safety signals have been identified. Infusion reactions are reported in <5% of cases. The rates of adverse events (AE), serious AEs, and serious infections were not different between patients treated with placebo and those who received vedolizumab in a pooled analysis of six randomized controlled trials. Rates of malignancy and mortality in vedolizumab-exposed patients are similar to those of the general UC patient population. Progressive multifocal leukoencephalopathy has not been observed. Vedolizumab is a safe and effective therapy for UC with a unique mechanism of action.

Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies

PubMed Central

Sinaci, A. Anil; Laleci Erturkmen, Gokce B.; Gonul, Suat; Yuksel, Mustafa; Invernizzi, Paolo; Thakrar, Bharat; Pacaci, Anil; Cinar, H. Alper; Cicekli, Nihan Kesim

2015-01-01

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. PMID:26543873

Once-Monthly Continuous Erythropoietin Receptor Activator (C.E.R.A.) in Patients with Hemodialysis-Dependent Chronic Kidney Disease: Pooled Data from Phase III Trials.

PubMed

Locatelli, Francesco; Choukroun, Gabriel; Truman, Matt; Wiggenhauser, Alfons; Fliser, Danilo

2016-04-01

Erythropoiesis-stimulating agents and iron are commonly used in patients with chronic kidney disease with the aim of correcting anemia and maintaining stable hemoglobin levels. We analyzed pooled data from 13 studies with similar designs included in the Umbrella Continuous Erythropoietin Receptor Activator (C.E.R.A.) program to investigate the effects of continuous erythropoiesis receptor activator in clinically relevant subgroups of patients with chronic kidney disease and to determine whether the efficacy and safety outcomes demonstrated in the overall chronic kidney disease population are maintained in specific subgroups. Data from 13 Phase III trials set up with similar design were retrospectively pooled for this analysis. Patients with chronic kidney disease who had previously been receiving epoetin or darbepoetin were switched to continuous erythropoiesis receptor activator once-monthly after a 4- to 8-week screening period. Patients entered a 16-week continuous erythropoiesis receptor activator dose-titration period followed by an 8-week evaluation period. In total, 2060 patients were included in the analysis. Subgroups were defined based on: hemoglobin target range [lower (10.0-12.0 g/dL)/upper (10.5-13.0 g/dL)], gender (female/male), age (<65/≥65), baseline N-terminal pro-B-type natriuretic peptide levels (<5000/≥5000), cardiovascular risk factors (diabetes/cardiac/vascular/none). Across all subgroups analyzed, switching from shorter-acting erythropoiesis-stimulating agents to continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin concentrations in a high proportion of patients (78%), with only moderate hemoglobin fluctuations and a low number of dose changes. The safety profile across subgroups was as expected based on pre-existing risk factors; observed increases in adverse events were attributable to underlying risk factors rather than study drug. This retrospective analysis of 13 trials showed that continuous erythropoiesis receptor activator once-monthly maintained stable hemoglobin levels across a number of clinically relevant patient subgroups, including those with higher inherent cardiovascular risk. The safety profile was consistent with that previously established in the chronic kidney disease population. CLINICALTRIALS. NCT00413894/NCT00545571/NCT00517413/NCT00560404/NCT00882713/NCT00550680/NCT00576303/NCT00660023/NCT00717821/NCT00642850/NCT00605293/NCT00661505/NCT00699348. F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study.

PubMed

Nogova, Lucia; Sequist, Lecia V; Perez Garcia, Jose Manuel; Andre, Fabrice; Delord, Jean-Pierre; Hidalgo, Manuel; Schellens, Jan H M; Cassier, Philippe A; Camidge, D Ross; Schuler, Martin; Vaishampayan, Ulka; Burris, Howard; Tian, G Gary; Campone, Mario; Wainberg, Zev A; Lim, Wan-Teck; LoRusso, Patricia; Shapiro, Geoffrey I; Parker, Katie; Chen, Xueying; Choudhury, Somesh; Ringeisen, Francois; Graus-Porta, Diana; Porter, Dale; Isaacs, Randi; Buettner, Reinhard; Wolf, Jürgen

2017-01-10

Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1-amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other solid tumors with FGFR genetic alterations (mutations/amplifications/fusions) received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week-off schedule (arm 3). Results Data in 132 patients from the escalation and expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was determined on the basis of dose-limiting toxicities in four patients (100 mg, grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1]; 150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1-week-off schedule (RP2D). However, adverse event-related dose adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial responses [six confirmed]) was demonstrated with BGJ398 doses ≥ 100 mg in patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer. Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile and showed antitumor activity in several tumor types, including FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancers.

Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

PubMed

McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

2015-01-01

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment.

PubMed

Consoli, Agostino; Formoso, Gloria; Baldassarre, Maria Pompea Antonia; Febo, Fabrizio

2018-03-01

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile. Area Covered: adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes. Expert opinion: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a 'similar' safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.

A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases.

PubMed

Verstockt, Bram; Deleenheer, Barbara; Van Assche, Gert; Vermeire, Séverine; Ferrante, Marc

2017-07-01

Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies. Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD. Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects.

PubMed

Franco, Valentina; Perucca, Emilio

2015-01-01

Phenytoin, a widely prescribed old-generation antiepileptic drug, requires careful individualization of dosage to compensate for its prominent pharmacokinetic variability. This article reviews the contribution of genetic polymorphisms affecting the activity of CYP2C9, the main enzyme responsible for phenytoin metabolism, to the variation in phenytoin clearance and susceptibility to adverse effects. Comprehensive and critical review of available evidence concerning the influence of CYP2C9 genetic polymorphism on phenytoin pharmacokinetic and safety profile. There is extensive evidence that CYP2C9 polymorphisms are an important determinant of the rate of phenytoin metabolism, although other factors including expression of other enzymes such as CYP2C19 and the influence of drug interactions, physiological and disease-related factors may also play a role. Patients carrying CYP2C9 genotypes associated with reduced phenytoin clearance are at greater risk of developing CNS adverse effects as well as serious cutaneous adverse reactions when given usual dosages of phenytoin. The clinical value and cost-effectiveness of CYP2C9 genotyping in improving the safety of phenytoin therapy, however, have not been clearly established and require formal testing in well-designed prospective studies.

Consensus achievement of leadership, organisational and individual factors that influence safety climate: Implications for nursing management.

PubMed

Fischer, Shelly A; Jones, Jacqueline; Verran, Joyce A

2018-01-01

To validate a framework of factors that influence the relationship of transformational leadership and safety climate, and to enable testing of safety chain factors by generating hypotheses regarding their mediating and moderating effects. Understanding the patient safety chain and mechanisms by which leaders affect a strong climate of safety is essential to transformational leadership practice, education, and research. A systematic review of leadership and safety literature was used to develop an organising framework of factors proposed to influence the climate of safety. A panel of 25 international experts in leadership and safety engaged a three-round modified Delphi study with Likert-scored surveys. Eighty per cent of participating experts from six countries were retained to the final survey round. Consensus (>66% agreement) was achieved on 40 factors believed to influence safety climate in the acute care setting. Consensus regarding specific factors that play important roles in an organisation's climate of safety can be reached. Generally, the demonstration of leadership commitment to safety is key to cultivating a culture of patient safety. Transformational nurse leaders should consider and employ all three categories of factors in daily leadership activities and decision-making to drive a strong climate of patient safety. © 2017 John Wiley & Sons Ltd.

The PANGAEA study design - a prospective, multicenter, non-interventional, long-term study on fingolimod for the treatment of multiple sclerosis in daily practice.

PubMed

Ziemssen, Tjalf; Kern, Raimar; Cornelissen, Christian

2015-06-18

Fingolimod (Gilenya) is an oral medication for patients with highly active relapsing-remitting Multiple Sclerosis (RRMS). Clinical trials and post-marketing experience on more than 114,000 patients have established a detailed safety profile. Total patient exposure now exceeds 195,000 patient-years as stated in the last financial report (Dec 2014) of the Novartis Pharma AG, Basel, Switzerland. However, less is known about the safety of long-term fingolimod use in daily practice. Here, we describe the study design of PANGAEA (Post-Authorization Non-interventional German sAfety of GilEnyA in RRMS patients), a prospective, multicenter, non-interventional, long-term study to collect safety, efficacy, and pharmacoeconomic data on RRMS patients treated with fingolimod (0.5 mg/daily) under real-world conditions in Germany. PANGAEA is striving to assess a real-world safety and efficacy profile of fingolimod, based on data from 4,000 RRMS patients, obtained during a 60-month observational phase. A pharmacoeconomic sub-study of 800 RRMS patients further collects patient-reported outcome measures of disability, quality of life, compliance, treatment satisfaction, and usage of resources during a 24-month observational phase. Descriptive statistical analyses of the safety set as well as of stratified subgroups such as patients with concomitant diabetes mellitus and pretreated patients (e.g., natalizumab) will be conducted. PANGAEA seeks to confirm the current safety profile of fingolimod obtained in phase I-III clinical trials. The study design presented here will additionally provide guidance on the therapeutic use of fingolimod in clinical practice and possibly assists physicians in making evidence-based decisions.

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience.

PubMed

Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

2014-05-01

To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010). Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Comparison on the Effects and Safety of Tualang Honey and Tribestan in Sperm Parameters, Erectile Function, and Hormonal Profiles among Oligospermic Males

PubMed Central

Ismail, Shaiful Bahari; Bakar, Mohd. Bustamanizan; Nik Hussain, Nik Hazlina; Sulaiman, Siti Amrah; Jaafar, Hasnan; Draman, Samsul; Ramli, Roszaman; Wan Yusoff, Wan Zahanim

2014-01-01

Introduction. This study aims to evaluate the effectiveness of Tualang honey on sperm parameters, erectile function, and hormonal and safety profiles. Methodology. A randomized control trial was done using Tualang honey (20 grams) and Tribestan (750 mg) over a period of 12 weeks. Sperm parameters including sperm concentration, motility, and morphology were analyzed and erectile function was assessed using IIEF-5 questionnaire. Hormonal profiles of testosterone, FSH, and LH were studied. The volunteers were randomized into two groups and the outcomes were analyzed using SPSS version 18. Results. A total of 66 participants were involved. A significant increment of mean sperm concentration (P < 0.001), motility (P = 0.015) and morphology (P = 0.008) was seen in Tualang honey group. In Tribestan group, a significant increment of mean sperm concentration (P = 0.007), and morphology (P = 0.009) was seen. No significant differences of sperm concentration, motility, and morphology were seen between Tualang honey and Tribestan group and similar results were also seen in erectile function and hormonal profile. All safety profiles were normal and no adverse event was reported. Conclusion. Tualang honey effect among oligospermic males was comparable with Tribestan in improving sperm concentration, motility, and morphology. The usage of Tualang honey was also safe with no reported adverse event. PMID:25505918

14 CFR 29.303 - Factor of safety.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Strength Requirements General § 29.303 Factor of safety. Unless otherwise provided, a factor of safety of 1.5 must be used. This factor applies to external and inertia... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Factor of safety. 29.303 Section 29.303...

14 CFR 27.303 - Factor of safety.

Code of Federal Regulations, 2010 CFR

2010-01-01

... STANDARDS: NORMAL CATEGORY ROTORCRAFT Strength Requirements General § 27.303 Factor of safety. Unless otherwise provided, a factor of safety of 1.5 must be used. This factor applies to external and inertia... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Factor of safety. 27.303 Section 27.303...

Pharmacokinetics and pharmacodynamics of multiple doses of BG00010, a neurotrophic factor with anti-hyperalgesic effects, in patients with sciatica.

PubMed

Okkerse, Pieter; Hay, Justin L; Versage, Eve; Tang, Yongqiang; Galluppi, Gerald; Ravina, Bernard; Verma, Ajay; Williams, Leslie; Aycardi, Ernesto; Groeneveld, Geert Jan

2016-07-01

BG00010 is a protein in the glial cell line-derived neurotrophic factor (GDNF) family. It is a selective ligand for the GDNF family receptor alpha-3 (GFRα3) co-receptor that normalizes cellular changes resulting from damage or disease, and potentially alleviates neuropathic pain. The main objectives of this study were to evaluate the pharmacokinetic and safety profiles and to determine the effects on pain of ascending doses of intravenous injections of BG00010 in patients with sciatica. This was a randomized, blinded, placebo-controlled multiple-dose study in subjects with sciatica. In Part I (16 patients), four IV dose levels were examined (50, 150, 400, 800 μg kg(-1) ) and in Part II (12 patients), three dose levels were examined (400, 600 and 1200 μg kg(-1) ). Safety and efficacy assessments were used as endpoints. The BG00010 concentration-time data indicated relatively low inter-patient variability and there was a dose-dependent (not dose-proportional) increase in serum exposure from 150 to 1200 μg kg(-1) . The effective half-life was between 40 and 60 h. The most frequently occurring adverse events (AEs) reported by patients receiving BG00010 were headache (67-83%), feeling hot (50-100%), and pruritus (42-67%). Most AEs were mild; no serious AEs or AEs leading to discontinuation occurred. Higher dose regimens of BG00010 resulted in greater pain reduction than placebo or lower dose regimens, although a clear dose-response relationship was not seen. The pharmacokinetic profile of BG00010 was characterized by low intra-patient variability. These data from a small sample suggest that BG00010 may have a benefit for patients with sciatica. © 2016 The British Pharmacological Society.

Selecting optimal second-generation antihistamines for allergic rhinitis and urticaria in Asia.

PubMed

Recto, Marysia Tiongco; Gabriel, Ma Teresita; Kulthanan, Kanokvalai; Tantilipikorn, Pongsakorn; Aw, Derrick Chen-Wee; Lee, Tak Hong; Chwen, Ch'ng Chin; Mutusamy, Somasundran; Hao, Nguyen Trong; Quang, Vo Thanh; Canonica, Giorgio Walter

2017-01-01

Allergic diseases are on the rise in many parts of the world, including the Asia-Pacific (APAC) region. Second-generation antihistamines are the first-line treatment option in the management of allergic rhinitis and urticaria. International guidelines describe the management of these conditions; however, clinicians perceive the additional need to tailor treatment according to patient profiles. This study serves as a consensus of experts from several countries in APAC (Hong Kong, Malaysia, the Philippines, Singapore, Thailand, Vietnam), which aims to describe the unmet needs, practical considerations, challenges, and key decision factors when determining optimal second-generation antihistamines for patients with allergic rhinitis and/or urticaria. Specialists from allergology, dermatology, and otorhinolaryngology were surveyed on practical considerations and key decision points when treating patients with allergic rhinitis and/or urticaria. Clinicians felt the need for additional tools for diagnosis of these diseases and a single drug with all preferred features of an antihistamine. Challenges in treatment include lack of clinician and patient awareness and compliance, financial constraints, and treatment for special patient populations such as those with concomitant disease. Selection of optimal second-generation antihistamines depends on many factors, particularly drug safety and efficacy, impact on psychomotor abilities, and sedation. Country-specific considerations include drug availability and cost-effectiveness. Survey results reveal bilastine as a preferred choice due to its high efficacy and safety, suitability for special patient populations, and the lack of sedative effects. Compliance to the international guidelines is present among allergists, dermatologists and otorhinolaryngologists; however, this is lower amongst general practitioners (GPs). To increase awareness, allergy education programs targeted at GPs and patients may be beneficial. Updates to the existing international guidelines are suggested in APAC to reflect appropriate management for different patient profiles and varying symptoms of allergic rhinitis and urticaria.

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa.

PubMed

Lentz, S R; Ehrenforth, S; Karim, F Abdul; Matsushita, T; Weldingh, K N; Windyga, J; Mahlangu, J N

2014-08-01

Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors. To confirm the safety and assess the efficacy of vatreptacog alfa in treating bleeding episodes in hemophilic patients with inhibitors. In this international, multicenter, randomized, double-blind, active-controlled, crossover, confirmatory phase III trial (adept(™) 2) in patients with hemophilia A or B and inhibitors, bleeds were randomized 3 : 2 to treatment with vatreptacog alfa (one to three doses at 80 μg kg(-1) ) or rFVIIa (one to three doses at 90 μg kg(-1) ). Treatment failures after three doses of trial product (TP) were managed according to the local standard of care. In the 72 patients enrolled, 567 bleeds were treated with TP. Both vatreptacog alfa and rFVIIa gave 93% effective bleeding control at 12 h. Vatreptacog alfa was superior to rFVIIa in secondary efficacy outcomes, including the number of doses used to treat a bleed and sustained bleeding control 24-48 h after the first dose. Eight patients (11%) developed antibodies against vatreptacog alfa, including four with cross-reactivity against rFVIIa and one with an in vitro neutralizing effect to vatreptacog alfa. This large randomized controlled trial confirmed the well-established efficacy and safety profile of rFVIIa, and showed that vatreptacog alfa had similar or better efficacy than rFVIIa. However, because of the development of anti-drug antibodies, a positive benefit-risk profile is unlikely to be achieved with vatreptacog alfa. © 2014 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Genetic variation in aryl N-acetyltransferase results in significant differences in the pharmacokinetic and safety profiles of amifampridine (3,4-diaminopyridine) phosphate.

PubMed

Haroldsen, Peter E; Garovoy, Marvin R; Musson, Donald G; Zhou, Huiyu; Tsuruda, Laurie; Hanson, Boyd; O'Neill, Charles A

2015-02-01

The clinical use of amifampridine phosphate for neuromuscular junction disorders is increasing. The metabolism of amifampridine occurs via polymorphic aryl N-acetyltransferase (NAT), yet its pharmacokinetic (PK) and safety profiles, as influenced by this enzyme system, have not been investigated. The objective of this study was to assess the effect of NAT phenotype and genotype on the PK and safety profiles of amifampridine in healthy volunteers (N = 26). A caffeine challenge test and NAT2 genotyping were used to delineate subjects into slow and fast acetylators for PK and tolerability assessment of single, escalating doses of amifampridine (up to 30 mg) and in multiple daily doses (20 mg QID) of amifampridine. The results showed that fast acetylator phenotypes displayed significantly lower C max, AUC, and shorter t 1/2 for amifampridine than slow acetylators. Plasma concentrations of the N-acetyl metabolite were approximately twofold higher in fast acetylators. Gender differences were not observed. Single doses of amifampridine demonstrated dose linear PKs. Amifampridine achieved steady state plasma levels within 1 day of dosing four times daily. No accumulation or time-dependent changes in amifampridine PK parameters occurred. Overall, slow acetylators reported 73 drug-related treatment-emergent adverse events versus 6 in fast acetylators. Variations in polymorphic NAT corresponding with fast and slow acetylator phenotypes significantly affects the PK and safety profiles of amifampridine.

Ohio traffic crash facts, 2007

DOT National Transportation Integrated Search

2008-05-07

The Ohio Department of Public Safety is pleased to present the 2007 Ohio Traffic Crash : Facts Book, an in-depth highway safety statistical profile and analysis compiled from : data supplied by law enforcement agencies from across the state. : This a...

Ohio traffic crash facts, 2008

DOT National Transportation Integrated Search

2009-07-01

The Ohio Department of Public Safety is pleased to present the 2008 Ohio Traffic Crash : Facts Book, an in-depth highway safety statistical profile and analysis compiled from : data supplied by law enforcement agencies from across the state. This ann...

Ohio traffic crash facts, 2009

DOT National Transportation Integrated Search

2010-11-01

The Ohio Department of Public Safety is pleased to present the 2009 Ohio Traffic Crash Facts Book, an in-depth highway safety statistical profile and analysis compiled from data supplied by law enforcement agencies from across the state. This annual ...

Safety and Efficacy of Microinvasive Glaucoma Surgery

PubMed Central

Chen, David Z.

2017-01-01

Microinvasive glaucoma surgery (MIGS) is emerging as a new therapeutic option for glaucoma patients who wish to reduce their medication burden and avoid the postoperative complications of conventional glaucoma filtration surgery. These devices differ in terms of their efficacy and safety profile. Schlemm's canal devices have the most favorable safety profile at the compromise of modest efficacy, while subconjunctival and suprachoroidal devices are potentially more effective at lowering the intraocular pressure at the expense of a higher rate of complications. This review consolidates the latest evidence on the efficacy and safety of the MIGS devices in clinical use and provides an overview on upcoming devices which would likely also become viable treatment options in the near future. These clinical data would assist a glaucoma surgeon in selecting the most appropriate MIGS device for each patient based on the glaucoma severity and patient expectations. PMID:28512578

Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

PubMed

Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert-Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul

2015-03-01

An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3-9 years. In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3-9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4(+) T cells with a TH 1 profile were observed. Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

How important is vehicle safety for older consumers in the vehicle purchase process?

PubMed

Koppel, Sjaan; Clark, Belinda; Hoareau, Effie; Charlton, Judith L; Newstead, Stuart V

2013-01-01

This study aimed to investigate the importance of vehicle safety to older consumers in the vehicle purchase process. Older (n = 102), middle-aged (n = 791), and younger (n = 109) participants throughout the eastern Australian states of Victoria, New South Wales, and Queensland who had recently purchased a new or used vehicle completed an online questionnaire about their vehicle purchase process. When asked to list the 3 most important considerations in the vehicle purchase process (in an open-ended format), older consumers were mostly likely to list price as their most important consideration (43%). Similarly, when presented with a list of vehicle factors (such as price, design, Australasian New Car Assessment Program [ANCAP] rating), older consumers were most likely to identify price as the most important vehicle factor (36%). When presented with a list of vehicle features (such as automatic transmission, braking, air bags), older consumers in the current study were most likely to identify an antilock braking system (41%) as the most important vehicle feature, and 50 percent of older consumers identified a safety-related vehicle feature as the highest priority vehicle feature (50%). When asked to list up to 3 factors that make a vehicle safe, older consumers in the current study were most likely to list braking systems (35%), air bags (22%), and the driver's behavior or skill (11%). When asked about the influence of safety in the new vehicle purchase process, one third of older consumers reported that all new vehicles are safe (33%) and almost half of the older consumers rated their vehicle as safer than average (49%). A logistic regression model was developed to predict the profile of older consumers more likely to assign a higher priority to safety features in the vehicle purchasing process. The model predicted that the importance of safety-related features was influenced by several variables, including older consumers' beliefs that they could protect themselves and their family from a crash, their traffic infringement history, and whether they had children. These findings are consistent with previous research that suggests that, though older consumers highlight the importance of safety features (i.e., seat belts, air bags, braking), they often downplay the role of safety in their vehicle purchasing process and are more likely to equate vehicle safety with the presence of specific vehicle safety features or technologies rather than the vehicle's crash safety/test results or crashworthiness. The findings from this study provide a foundation to support further research in this area that can be used by policy makers, manufacturers, and other stakeholders to better target the promotion and publicity of vehicle safety features to particular consumer groups (such as older consumers). Better targeted campaigns may help to emphasize the value of safety features and their role in reducing the risk of injury/death. If older consumers are better informed of the benefits of safety features when purchasing a vehicle, a further reduction in injuries and deaths related to motor vehicle crashes may be realized.

Analysis of factors influencing safety management for metro construction in China.

PubMed

Yu, Q Z; Ding, L Y; Zhou, C; Luo, H B

2014-07-01

With the rapid development of urbanization in China, the number and size of metro construction projects are increasing quickly. At the same time, and increasing number of accidents in metro construction make it a disturbing focus of social attention. In order to improve safety management in metro construction, an investigation of the participants' perspectives on safety factors in China metro construction has been conducted to identify the key safety factors, and their ranking consistency among the main participants, including clients, consultants, designers, contractors and supervisors. The result of factor analysis indicates that there are five key factors which influence the safety of metro construction including safety attitude, construction site safety, government supervision, market restrictions and task unpredictability. In addition, ANOVA and Spearman rank correlation coefficients were performed to test the consistency of the means rating and the ranking of safety factors. The results indicated that the main participants have significant disagreement about the importance of safety factors on more than half of the items. Suggestions and recommendations on practical countermeasures to improve metro construction safety management in China are proposed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structural Deterministic Safety Factors Selection Criteria and Verification

NASA Technical Reports Server (NTRS)

Verderaime, V.

1992-01-01

Though current deterministic safety factors are arbitrarily and unaccountably specified, its ratio is rooted in resistive and applied stress probability distributions. This study approached the deterministic method from a probabilistic concept leading to a more systematic and coherent philosophy and criterion for designing more uniform and reliable high-performance structures. The deterministic method was noted to consist of three safety factors: a standard deviation multiplier of the applied stress distribution; a K-factor for the A- or B-basis material ultimate stress; and the conventional safety factor to ensure that the applied stress does not operate in the inelastic zone of metallic materials. The conventional safety factor is specifically defined as the ratio of ultimate-to-yield stresses. A deterministic safety index of the combined safety factors was derived from which the corresponding reliability proved the deterministic method is not reliability sensitive. The bases for selecting safety factors are presented and verification requirements are discussed. The suggested deterministic approach is applicable to all NASA, DOD, and commercial high-performance structures under static stresses.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

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

Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs)more » as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.« less

Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis with high retention rate: 3-year results from the phase III trial, MEASURE 2.

PubMed

Marzo-Ortega, Helena; Sieper, Joachim; Kivitz, Alan; Blanco, Ricardo; Cohen, Martin; Delicha, Evie-Maria; Rohrer, Susanne; Richards, Hanno

2017-01-01

Secukinumab treatment has previously been shown to significantly improve the signs and symptoms of active ankylosing spondylitis (AS), with responses sustained through 2 years. Here, we report the long-term (3 years) efficacy and safety of secukinumab in the MEASURE 2 study. MEASURE 2 (NCT01649375) is a 5-year phase III, randomised, double-blind, double-dummy, parallel-group, placebo-controlled study to evaluate the efficacy, safety and tolerability of subcutaneous loading and maintenance dosing of secukinumab in adult subjects with active AS. Subjects were randomised to receive subcutaneous secukinumab 150 mg, 75 mg or placebo at baseline, weeks 1, 2 and 3 and every 4 weeks from week 4. At week 16, placebo-treated subjects were rerandomised to receive secukinumab 150/75 mg. Retention rates were high during weeks 16-156 and were 86% and 76% for secukinumab 150 and 75 mg, respectively. Secukinumab 150 mg provided sustained improvements in the Assessment of Spondyloarthritis International Society ASAS 20/40 response rates at week 156 (70.1%/60.9%) compared with week 52 (74.2%/57.0%); however, there was a slight decrease for secukinumab 75 mg (54.3%/37.0% vs 62.5%/43.2%, respectively). Sustained improvements were observed in all other end points, including Bath Ankylosing Spondylitis Disease Activity Index, AS Disease Activity Score with C reactive protein inactive disease, ASAS 5/6, Short Form-36 Physical Component Summary and ASAS partial remission. Clinical benefits were observed regardless of prior exposure to anti-tumour necrosis factor agents. The safety profile remained favourable and was consistent with previous reports. This study showed sustained improvement through 3 years in signs, symptoms and physical function in subjects with AS. Retention rates were high and secukinumab was well tolerated, with a favourable safety profile.

The effects of the non-contingent presentation of safety signals on the elimination of safety behaviors: An experimental comparison between individuals with low and high obsessive-compulsive profiles.

PubMed

Angelakis, Ioannis; Austin, Jennifer L

2018-06-01

Safety behaviors, defined as engagement in avoidance within safe environments, are a key symptom of obsessive-compulsive and related disorders. They may interfere with daily functioning and as such their emission should be reduced. The purpose of the current study is to investigate the effects of the non-contingent presentation of safety signals (cues produced by safety behaviors) on reducing safety behaviors in participants self-reporting low and high OCD profiles. In total, 32 participants were asked to play a game to gain points and avoid their loss. After having developed avoidance behavior, evidenced by maintaining all of their earned points, they were exposed to safe environments where no point loss was programmed. In Test 1, safety cues (blue bar) were produced contingent on performing safety behaviors. In Test 2, safety cues were presented continuously without any response requirement. Findings demonstrated that high OCD group displayed higher rates of safety behaviors than low OCD group. However, exposure to the non-contingent presentation of safety signals eliminated their emission in both groups. Future studies need to evaluate the effects of different non-contingent schedules on the suppression of safety behaviors. These findings contribute to the literature by demonstrating that non-contingent introduction of safety signals eliminated safety behaviors completely, even in high OCD participants, who performed safety behavior at higher rates. Such a treatment protocol may ameliorate exposure therapy in which response prevention constitutes a key element and is generally associated with increased drop-out rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

NASA African American History Month Profile - Kimberly Ennix-Sandhu (AFRC)

NASA Image and Video Library

2018-02-20

Kimberly Ennix-Sandhu is the SOFIA Operations Center System Safety Lead at NASA Armstrong Flight Research Center. SOFIA is the Stratospheric Observatory for Infrared Astronomy. Kimberly has worked for NASA for 27 years. She started out in jet and rocket propulsion research engineering and moved to Safety and Mission Assurance as a system safety engineer.

Summary of School Safety Statistics. National Institute of Justice Report

ERIC Educational Resources Information Center

Carlton, Mary Poulin

2017-01-01

Several high-profile incidents of violence at U.S. schools have, understandably, raised concerns about the safety of students while at school. Just one incident of violence causes significant harm. In light of this, it is important to examine commonly held beliefs about school safety and violence because they sometimes reflect a misperception or…

2009 Human Factors and Roadway Safety Workshop : Teen Driver Safety [SD .WMV (720x480/29fps/177.0 MB)

DOT National Transportation Integrated Search

2009-11-05

Iowa Department of Transportation Research and Technology Bureau video presentation from the 2009 human factors and roadway safety workshop session titled: Teen Driver Safety : Keynote Speaker Dan McGehee, director, Human Factors & Vehicle Safety Res...

A structural equation modelling approach examining the pathways between safety climate, behaviour performance and workplace slipping

PubMed Central

Swedler, David I; Verma, Santosh K; Huang, Yueng-Hsiang; Lombardi, David A; Chang, Wen-Ruey; Brennan, Melayne; Courtney, Theodore K

2015-01-01

Objective Safety climate has previously been associated with increasing safe workplace behaviours and decreasing occupational injuries. This study seeks to understand the structural relationship between employees’ perceptions of safety climate, performing a safety behaviour (ie, wearing slip-resistant shoes) and risk of slipping in the setting of limited-service restaurants. Methods At baseline, we surveyed 349 employees at 30 restaurants for their perceptions of their safety training and management commitment to safety as well as demographic data. Safety performance was identified as wearing slip-resistant shoes, as measured by direct observation by the study team. We then prospectively collected participants’ hours worked and number of slips weekly for the next 12 weeks. Using a confirmatory factor analysis, we modelled safety climate as a higher order factor composed of previously identified training and management commitment factors. Results The 349 study participants experienced 1075 slips during the 12-week follow-up. Confirmatory factor analysis supported modelling safety climate as a higher order factor composed of safety training and management commitment. In a structural equation model, safety climate indirectly affected prospective risk of slipping through safety performance, but no direct relationship between safety climate and slips was evident. Conclusions Results suggest that safety climate can reduce workplace slips through performance of a safety behaviour as well as suggesting a potential causal mechanism through which safety climate can reduce workplace injuries. Safety climate can be modelled as a higher order factor composed of safety training and management commitment. PMID:25710968

Ohio traffic crash facts, 2010

DOT National Transportation Integrated Search

2011-10-01

The Ohio Department of Public Safety is pleased to present the 2010 Ohio Traffic Crash Facts Book, an in-depth highway safety profile and analysis compiled from data supplied by law enforcement agencies across the state. This annual report provides a...

Motor carrier safety performance profile.

DOT National Transportation Integrated Search

2004-02-01

This report provides a summary of the safety performance of carriers across all the individual segments in the industry. It includes summaries for both for-hire and private carriers in each segment and is drawn from measures that are collected as par...

Patient- and lesion-tailored algorithm of endovascular treatment for arterial occlusive disease of extracranial arteries supplying the brain: safety of the treatment at 30-day follow-up

PubMed Central

Simka, Marian; Brzegowy, Paweł; Janas, Piotr; Kazibudzki, Marek; Pieniążek, Piotr; Ochała, Andrzej; Popiela, Tadeusz; Mrowiecki, Tomasz

2017-01-01

Introduction Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, stenting plays an important role as an alternative treatment modality, especially in high-risk patients. The actual safety profile associated with stenting procedures is probably better than that reported by randomized controlled trials. Aim To assess the safety of stent implantations in extracranial arteries supplying the brain, and also to identify risk factors associated with this procedure. Material and methods This was a post hoc analysis, with 30-day follow-up. We analyzed the results of treatment of 372 patients who underwent 408 procedures, 197 such procedures in asymptomatic, and 211 in symptomatic individuals. Stenting procedures were performed using a technique and armamentarium which were tailored to the type and anatomy of lesions. Results There were 6 (1.5%) strokes, including 2 (0.5%) major strokes, 1 ipsi- and 1 contralateral, and 4 (1.0%) minor strokes. In asymptomatic patients there was 1 (0.3%) minor stroke. Transient ischemic attacks occurred in 5 (1.2%) patients. There were 2 (0.5%) non-STEMI myocardial infarctions and 2 (0.5%) non-stroke related fatalities. Risk factors of these adverse events were diabetes mellitus, lesions localized in a tortuous segment of the artery, embolic material in the filter and bilateral stenoses of carotid arteries. Additional risk factors in asymptomatic patients were renal impairment and advanced coronary artery disease; and in symptomatic patients, grade 3 arterial hypertension, dislipidemia, cigarette smoking and lesions requiring predilatation. Conclusions Stenting procedures of extracranial arteries supplying the brain, which are tailored to the type and anatomy of lesions, seem to be relatively safe. PMID:28344618

Patient- and lesion-tailored algorithm of endovascular treatment for arterial occlusive disease of extracranial arteries supplying the brain: safety of the treatment at 30-day follow-up.

PubMed

Latacz, Paweł; Simka, Marian; Brzegowy, Paweł; Janas, Piotr; Kazibudzki, Marek; Pieniążek, Piotr; Ochała, Andrzej; Popiela, Tadeusz; Mrowiecki, Tomasz

2017-01-01

Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, stenting plays an important role as an alternative treatment modality, especially in high-risk patients. The actual safety profile associated with stenting procedures is probably better than that reported by randomized controlled trials. To assess the safety of stent implantations in extracranial arteries supplying the brain, and also to identify risk factors associated with this procedure. This was a post hoc analysis, with 30-day follow-up. We analyzed the results of treatment of 372 patients who underwent 408 procedures, 197 such procedures in asymptomatic, and 211 in symptomatic individuals. Stenting procedures were performed using a technique and armamentarium which were tailored to the type and anatomy of lesions. There were 6 (1.5%) strokes, including 2 (0.5%) major strokes, 1 ipsi- and 1 contralateral, and 4 (1.0%) minor strokes. In asymptomatic patients there was 1 (0.3%) minor stroke. Transient ischemic attacks occurred in 5 (1.2%) patients. There were 2 (0.5%) non-STEMI myocardial infarctions and 2 (0.5%) non-stroke related fatalities. Risk factors of these adverse events were diabetes mellitus, lesions localized in a tortuous segment of the artery, embolic material in the filter and bilateral stenoses of carotid arteries. Additional risk factors in asymptomatic patients were renal impairment and advanced coronary artery disease; and in symptomatic patients, grade 3 arterial hypertension, dislipidemia, cigarette smoking and lesions requiring predilatation. Stenting procedures of extracranial arteries supplying the brain, which are tailored to the type and anatomy of lesions, seem to be relatively safe.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

PubMed Central

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

2016-01-01

Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

14 CFR 23.303 - Factor of safety.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Factor of safety. 23.303 Section 23.303... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Structure General § 23.303 Factor of safety. Unless otherwise provided, a factor of safety of 1.5 must be used. ...

Alopecia areata: a new treatment plan

PubMed Central

Alsantali, Adel

2011-01-01

Many therapeutic modalities have been used to treat alopecia areata, with variable efficacy and safety profiles. Unfortunately, none of these agents is curative or preventive. Also, many of these therapeutic agents have not been subjected to randomized, controlled trials, and, except for topical immunotherapy, there are few published studies on long-term outcomes. The treatment plan is designed according to the patient’s age and extent of disease. In this paper, the therapeutic agents are organized according to their efficacy and safety profiles into first-line, second-line, and third-line options. PMID:21833161

A cross-cultural study of organizational factors on safety: Japanese vs. Taiwanese oil refinery plants.

PubMed

Hsu, Shang Hwa; Lee, Chun-Chia; Wu, Muh-Cherng; Takano, Kenichi

2008-01-01

This study attempts to identify idiosyncrasies of organizational factors on safety and their influence mechanisms in Taiwan and Japan. Data were collected from employees of Taiwanese and Japanese oil refinery plants. Results show that organizational factors on safety differ in the two countries. Organizational characteristics in Taiwanese plants are highlighted as: higher level of management commitment to safety, harmonious interpersonal relationship, more emphasis on safety activities, higher devotion to supervision, and higher safety self-efficacy, as well as high quality of safety performance. Organizational characteristics in Japanese plants are highlighted as: higher level of employee empowerment and attitude towards continuous improvement, more emphasis on systematic safety management approach, efficient reporting system and teamwork, and high quality of safety performance. The casual relationships between organizational factors and workers' safety performance were investigated using structural equation modeling (SEM). Results indicate that the influence mechanisms of organizational factors in Taiwan and Japan are different. These findings provide insights into areas of safety improvement in emerging countries and developed countries respectively.

Bazedoxifene/conjugated estrogens for managing the burden of estrogen deficiency symptoms.

PubMed

Mirkin, Sebastian; Ryan, Kelly A; Chandran, Arthi B; Komm, Barry S

2014-01-01

The bothersome vasomotor and vaginal symptoms and bone loss that accompany the menopausal transition are associated with significant direct costs due to physician visits and medication, as well as indirect costs from reduced health-related quality of life (HRQoL) and work productivity. With life expectancies increasing, the number of postmenopausal women is also increasing, and more women are remaining in the workforce. These factors have led to an increased burden of menopausal symptoms on healthcare systems. Hormone therapy (HT) has been shown to effectively reduce menopausal symptoms and significantly increase quality-adjusted life years in postmenopausal women, particularly in women experiencing severe symptoms. However, many women discontinue use of HT before their symptoms have dissipated due to safety and tolerability concerns. The tissue selective estrogen complex (TSEC) that pairs bazedoxifene (BZA) with conjugated estrogens (CE) has been developed to provide relief of menopausal symptoms and prevent bone loss without stimulating the breast or endometrium, and to have improved tolerability compared with HT. In this context, BZA 20mg/CE 0.45 and 0.625 mg were shown to prevent bone loss and effectively treat menopausal symptoms in postmenopausal women with an intact uterus, while also demonstrating a favorable safety/tolerability profile. BZA 20mg/CE 0.45 and 0.625 mg were further associated with clinically significant improvements in HRQoL, sleep, and treatment satisfaction. Taken together, the reduction in menopausal symptoms, improvement in HRQoL, and favorable safety/tolerability profile associated with BZA/CE suggest that it is a cost-effective alternative to HT for managing the burden of menopausal symptoms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Organizational factors affecting safety implementation in food companies in Thailand.

PubMed

Chinda, Thanwadee

2014-01-01

Thai food industry employs a massive number of skilled and unskilled workers. This may result in an industry with high incidences and accident rates. To improve safety and reduce the accident figures, this paper investigates factors influencing safety implementation in small, medium, and large food companies in Thailand. Five factors, i.e., management commitment, stakeholders' role, safety information and communication, supportive environment, and risk, are found important in helping to improve safety implementation. The statistical analyses also reveal that small, medium, and large food companies hold similar opinions on the risk factor, but bear different perceptions on the other 4 factors. It is also found that to improve safety implementation, the perceptions of safety goals, communication, feedback, safety resources, and supervision should be aligned in small, medium, and large companies.

Investigation of structural factors of safety for the space shuttle

NASA Technical Reports Server (NTRS)

1972-01-01

A study was made of the factors governing the structural design of the fully reusable space shuttle booster to establish a rational approach to select optimum structural factors of safety. The study included trade studies of structural factors of safety versus booster service life, weight, cost, and reliability. Similar trade studies can be made on other vehicles using the procedures developed. The major structural components of a selected baseline booster were studied in depth, each being examined to determine the fatigue life, safe-life, and fail-safe capabilities of the baseline design. Each component was further examined to determine its reliability and safety requirements, and the change of structural weight with factors of safety. The apparent factors of safety resulting from fatigue, safe-life, proof test, and fail-safe requirements were identified. The feasibility of reduced factors of safety for design loads such as engine thrust, which are well defined, was examined.

Site characterization and evaluation of the stability of the Yesilyurt Landslide (Trabzon, NE Turkey) using back analysis method

NASA Astrophysics Data System (ADS)

Kul Yahşi, Bilgehan; Ersoy, Hakan

2018-06-01

The aim of this study was to determine the soil profile of the Yeşilyurt Landslide Area (NE Turkey) and to investigate the stability of the landslide area after the excavation planned by back analysis for support design. For these purposes, after the 1/1000 scaled engineering geological map was prepared, seismic refraction, electrical resistivity tomography and ground penetrating radar measurements were performed on different profiles to understand vertical and horizontal homogeneity of the landslide materials and undisturbed/disturbed soil samples were obtained from the test pits to determine the geotechnical properties of the soil. The results of the geophysical measurements showed that the landslide material was composed of two different soil zones. While the maximum thickness of the upper zone is 2.5, the thickness of the lower zone is about 5 m. The depth of dasidic rock mass is about 7 m. Residual cohesions of the soil samples obtained upper and lower zones were determined as 38 kPa and 44 kPa, and their residual friction angles were determined as 18° and 15° respectively. Unit weight values of the soil samples obtained from both zones were 16.9 kN m-3. The data obtained from laboratory tests showed that the landslide material is a uniform lithology. The geophysical measurements indicate that the wave velocity and resistivity values of these profiles differ from each other due to groundwater at a depth of 2.5 m. Limit equilibrium analysis were carried out with Slide v5.0 software using data obtained from the field measurements and laboratory tests to evaluate current and supported cases of the studied area. Because the safety factor of the slope obtained from the LE analyses is 0.99 and the studied soil environment is considered as unstable, the reliable and economical reinforcement was suggested using the retaining wall. The back-analysis method was evaluated to ensure the stability for a 1.5 safety factor and finally the lateral active forces for the retaining wall were calculated in the LE analysis as 718 kN and 1839 kN for without and with seismic load respectively.

Field validation of Tasmania's aquaculture industry bounce-diving schedules using Doppler analysis of decompression stress.

PubMed

Smart, David R; Van den Broek, Cory; Nishi, Ron; Cooper, P David; Eastman, David

2014-09-01

Tasmania's aquaculture industry produces over 40,000 tonnes of fish annually, valued at over AUD500M. Aquaculture divers perform repetitive, short-duration bounce dives in fish pens to depths up to 21 metres' sea water (msw). Past high levels of decompression illness (DCI) may have resulted from these 'yo-yo' dives. This study aimed to assess working divers, using Doppler ultrasonic bubble detection, to determine if yo-yo diving was a risk factor for DCI, determine dive profiles with acceptable risk and investigate productivity improvement. Field data were collected from working divers during bounce diving at marine farms near Hobart, Australia. Ascent rates were less than 18 m·min⁻¹, with routine safety stops (3 min at 3 msw) during the final ascent. The Kisman-Masurel method was used to grade bubbling post dive as a means of assessing decompression stress. In accordance with Defence Research and Development Canada Toronto practice, dives were rejected as excessive risk if more than 50% of scores were over Grade 2. From 2002 to 2008, Doppler data were collected from 150 bounce-dive series (55 divers, 1,110 bounces). Three series of bounce profiles, characterized by in-water times, were validated: 13-15 msw, 10 bounces inside 75 min; 16-18 msw, six bounces inside 50 min; and 19-21 msw, four bounces inside 35 min. All had median bubble grades of 0. Further evaluation validated two successive series of bounces. Bubble grades were consistent with low-stress dive profiles. Bubble grades did not correlate with the number of bounces, but did correlate with ascent rate and in-water time. These data suggest bounce diving was not a major factor causing DCI in Tasmanian aquaculture divers. Analysis of field data has improved industry productivity by increasing the permissible number of bounces, compared to earlier empirically-derived tables, without compromising safety. The recommended Tasmanian Bounce Diving Tables provide guidance for bounce diving to a depth of 21 msw, and two successive bounce dive series in a day's diving.

14 CFR 31.25 - Factor of safety.

Code of Federal Regulations, 2010 CFR

2010-01-01

... envelope stress. (c) A factor of safety of at least five must be used in the design of all fibrous or non... any single failure will not jeopardize safety of flight. (d) In applying factors of safety, the effect...

75 FR 39535 - Agency Information Collection Activities; Proposed Collection; Comment Request; Adverse Event...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... Safety Network (MedSun). Additionally, the electronic form will include hospital profile information and... Device-Safety Exchange (DS-X) (formerly called M-Den), which was a moderated site where MedSun members... emerging [[Page 39536

14 CFR 25.303 - Factor of safety.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Factor of safety. 25.303 Section 25.303... STANDARDS: TRANSPORT CATEGORY AIRPLANES Structure General § 25.303 Factor of safety. Unless otherwise specified, a factor of safety of 1.5 must be applied to the prescribed limit load which are considered...

The Public Safety Impact of Community Notification Laws: Rearrest of Convicted Sex Offenders

ERIC Educational Resources Information Center

Freeman, Naomi J.

2012-01-01

Sex offender management is one of the highest-profile issues in public safety today. Although states have enacted community notification laws as a means to protect communities from sexual offending, limited research has been conducted to examine the impact of these laws on public safety. As such, this study used a quasi-experimental design to…

Imaging motional Stark effect measurements at ASDEX Upgrade

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

Ford, O. P.; Burckhart, A.; McDermott, R.

2016-11-15

This paper presents an overview of results from the Imaging Motional Stark Effect (IMSE) diagnostic obtained during its first measurement campaign at ASDEX Upgrade since installation as a permanent diagnostic. A brief overview of the IMSE technique is given, followed by measurements of a standard H-mode discharge, which are compared to equilibrium reconstructions showing good agreement where expected. The development of special discharges for the calibration of pitch angle is reported and safety factor profile changes during sawteeth crashes are shown, which can be resolved to a few percent due to the high sensitivity at good time resolution of themore » new IMSE system.« less

Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices.

PubMed

Zhao, Chan; Zhang, Meifen

2017-04-10

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.

Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.

PubMed

García-Doval, I; Hernández, M V; Vanaclocha, F; Sellas, A; de la Cueva, P; Montero, D

2017-03-01

Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. © 2016 British Association of Dermatologists.

Can Disproportionality Analysis of Post-marketing Case Reports be Used for Comparison of Drug Safety Profiles?

PubMed

Michel, Christiane; Scosyrev, Emil; Petrin, Michael; Schmouder, Robert

2017-05-01

Clinical trials usually do not have the power to detect rare adverse drug reactions. Spontaneous adverse reaction reports as for example available in post-marketing safety databases such as the FDA Adverse Event Reporting System (FAERS) are therefore a valuable source of information to detect new safety signals early. To screen such large data-volumes for safety signals, data-mining algorithms based on the concept of disproportionality have been developed. Because disproportionality analysis is based on spontaneous reports submitted for a large number of drugs and adverse event types, one might consider using these data to compare safety profiles across drugs. In fact, recent publications have promoted this practice, claiming to provide guidance on treatment decisions to healthcare decision makers. In this article we investigate the validity of this approach. We argue that disproportionality cannot be used for comparative drug safety analysis beyond basic hypothesis generation because measures of disproportionality are: (1) missing the incidence denominators, (2) subject to severe reporting bias, and (3) not adjusted for confounding. Hypotheses generated by disproportionality analyses must be investigated by more robust methods before they can be allowed to influence clinical decisions.

Assessment of the effects of naringenin-type flavanones in uterus and vagina.

PubMed

Keiler, Annekathrin Martina; Dörfelt, Peggy; Chatterjee, Namita; Helle, Janina; Bader, Manuela I; Vollmer, Günter; Kretzschmar, Georg; Kuhlee, Franziska; Thieme, Detlef; Zierau, Oliver

2015-01-01

The potential utilization of plant secondary metabolites possessing estrogenic properties as alternatives to the classical hormone replacement therapy (HRT) for the relief of postmenopausal complaints asks for an evaluation regarding the safety in reproductive organs. In order to contribute to the estimation of the safety profile of the flavanones naringenin (Nar), 8‑prenylnaringenin (8PN) and 6‑(1,1‑dimethylally) naringenin (6DMAN), we investigated uterus and vagina derived from a three‑day uterotrophic assay in rats. Also, we investigated the metabolite profile resulting from the incubation of the three substances with liver microsomes. While no metabolites were detectable for naringenin, hydroxylation products were observed for 8PN and 6DMAN after incubation with human as well as rat liver microsomes. The parent compound naringenin did not evoke any estrogenic responses in the investigated parameters. A significant increase of the uterine wet weight, uterine epithelial thickness and proliferating vaginal cells was observed in response to 8PN, questioning the safety of 8PN if applied in the human situation. In contrast, no estrogenic effects on the reproductive organs were observed for 6DMAN in the conducted study, rendering it the compound with a more promising safety profile, therefore justifying further investigations into its efficacy to alleviate postmenopausal discomforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety of Novel Microbes for Human Consumption: Practical Examples of Assessment in the European Union

PubMed Central

Brodmann, Theodor; Endo, Akihito; Gueimonde, Miguel; Vinderola, Gabriel; Kneifel, Wolfgang; de Vos, Willem M.; Salminen, Seppo; Gómez-Gallego, Carlos

2017-01-01

Novel microbes are either newly isolated genera and species from natural sources or bacterial strains derived from existing bacteria. Novel microbes are gaining increasing attention for the general aims to preserve and modify foods and to modulate gut microbiota. The use of novel microbes to improve health outcomes is of particular interest because growing evidence points to the importance of gut microbiota in human health. As well, some recently isolated microorganisms have promise for use as probiotics, although in-depth assessment of their safety is necessary. Recent examples of microorganisms calling for more detailed evaluation include Bacteroides xylanisolvens, Akkermansia muciniphila, fructophilic lactic acid bacteria (FLAB), and Faecalibacterium prausnitzii. This paper discusses each candidate's safety evaluation for novel food or novel food ingredient approval according to European Union (EU) regulations. The factors evaluated include their beneficial properties, antibiotic resistance profiling, history of safe use (if available), publication of the genomic sequence, toxicological studies in agreement with novel food regulations, and the qualified presumptions of safety. Sufficient evidences have made possible to support and authorize the use of heat-inactivated B. xylanisolvens in the European Union. In the case of A. muciniphila, the discussion focuses on earlier safety studies and the strain's suitability. FLAB are also subjected to standard safety assessments, which, along with their proximity to lactic acid bacteria generally considered to be safe, may lead to novel food authorization in the future. Further research with F. prausnitzii will increase knowledge about its safety and probiotic properties and may lead to its future use as novel food. Upcoming changes in EUU Regulation 2015/2283 on novel food will facilitate the authorization of future novel products and might increase the presence of novel microbes in the food market. PMID:28955311

Assessment of Submarine Slope Stability on the Continental Margin off SW Taiwan

NASA Astrophysics Data System (ADS)

Hsu, Huai-Houh; Dong, Jia-Jyun; Cheng, Win-Bin; Su, Chih-Chieh

2017-04-01

The abundant gas hydrate reservoirs are distributed in the southwest (SW) off Taiwan. To explore this new energy, geological methods were systematically used and mainly emphasized on the storage potential evaluation. On the other hand, the correlation between gas hydrate dissociation and submarine slope stability is also an important issue. In this study, three submarine profiles on the active and passive continental margin were selected and assessed their slope stabilities by considering two influence factors (seismic forces and number of sedimentary layers). The gravity corers obtained from these three sites (Xiaoliuqiu, Yuan-An Ridge, and Pointer Ridge) to conduct soil laboratory tests. The physical property tests and isotropically consolidated undrained (CIU) triaxial tests were carried out to establish reference properties and shear strength parameters. Before the stability analysis is performed, it is also necessary to construct the seabed profile. For each submarine profile, data from P-waves and from S-waves generated by P-S conversion on reflection from airgun shots recorded along one line of ocean bottom seismometers were used to construct 2-D velocity sections. The seabed strata could be simplified to be only one sedimentary layer or to be multilayer in accordance with the velocity structure profile. Results show the safety factors (FS) of stability analysis are obviously different in considering the number of sedimentary layers, especially for a very thin layer of sediments on a steep slope. The simplified strata condition which treated all seabed strata as only one sedimentary layer might result in the FS lower than 1 and the slope was in an unstable state. On the contrary, the FS could be higher than 10 in a multilayer condition.

Laser safety at high profile projects

NASA Astrophysics Data System (ADS)

Barat, K.

2011-03-01

Laser Safety at high profile laser facilities tends to be more controlled than in the standard laser lab found at a research institution. The reason for this is the potential consequences for such facilities from incidents. This ranges from construction accidents, to equipment damage to personnel injuries. No laser user wants to sustain a laser eye injury. Unfortunately, many laser users, most commonly experienced researchers and inexperienced graduate students, do receive laser eye injuries during their careers. . More unforgiveable is the general acceptance of this scenario, as part of the research & development experience. How do senior researchers, safety personnel and management stop this trend? The answer lies in a cultural change that involves institutional training, user mentoring, hazard awareness by users and administrative controls. None of these would inhibit research activities. As a matter of fact, proper implementation of these controls would increase research productivity. This presentation will review and explain the steps needed to steer an institution, research division, group or individual lab towards a culture that should nearly eliminate laser accidents. As well as how high profile facilities try to avoid laser injuries. Using the definition of high profile facility as one who's funding in the million to billions of dollars or Euros and derives form government funding.

[Immunological adjuvants. Determinant factors in the efficacy-toxicity ratio of the contemporary vaccines].

PubMed

Batista-Duharte, Alexander; Lastre, Miriam; Pérez, Oliver

2014-02-01

To achieve effective and safe vaccines for the prevention of not yet controlled or re-emergent infectious diseases, one of the more importance aspects is to have immunological adjuvants that allow inducing a protective immune response with an appropriate safety profile. Since 1926 the aluminium compounds have been used as adjuvants for human vaccines, and only in the last 10 years have some new products been registered. Although there an enormous quantity of proposed candidates, the toxicity is the main factor that has limited their introduction into the clinic. In this work the mechanism of action are updated, and the toxicity of the immunological adjuvants are revised, especially those that have obtained clinical approval or are close to getting it. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The challenge of compiling data profiles to stimulate local preventive health action: a European case study from child safety.

PubMed

Alexander, Denise; Rigby, Michael; Gissler, Mika; Köhler, Lennart; MacKay, Morag

2015-05-01

Positive recent experience of presenting comparative child safety data at national level has instigated policy action in Europe. It was hoped a Child Safety Index could quantify how safe a community, region or locality is for its children in comparison with similar areas within Europe, as a focus for local targeted action. Validated indicators proposed by previous European projects identified from areas of child injury prevention, such as road safety, burns or poisoning, were selected to give a balanced profile, and populated from available published data. An index using a sub-score for each specific injury topic was proposed. The indicators' presentation, sensitivity and appropriateness were considered, as well as data availability. Satisfactory indicators were not identified for all areas and very few local area data were available. This forced the researchers to conclude that at present, constructing a reliable Child Safety Index for use at the local level is not feasible. There is a worrying lack of data available at the sub-national level to support injury prevention, evaluate interventions, and enable informed local decision making.

Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414) in Indian infants.

PubMed

Narang, Anil; Bose, Anuradha; Pandit, Anand Nilkanth; Dutta, Phalguni; Kang, Gagandeep; Bhattacharya, Sujit Kumar; Datta, Sanjoy Kumar; Suryakiran, P V; Delem, Andrée; Han, Htay Htay; Bock, Hans Ludwig

2009-06-01

This study was undertaken to assess the immunogenicity, reactogenicity and safety of two doses of an oral live-attenuated human rotavirus vaccine, strain RIX4414 (Rotarix()) in an Indian setting. The seroconversion rate observed one month post-dose 2 in the RIX4414 group 58.3% [95% CI: 48.7; 67.4] was significantly higher when compared to the placebo group 6.3%; [95% CI: 2.5; 12.5]. The reactogenicity and safety profile was similar for both groups. Healthy infants (N = 363), approximately eight weeks of age were enrolled to receive two doses of RIX4414 vaccine (n = 182) or placebo (n = 181) separated by one month. To assess the immune response, blood samples were taken before vaccination and one month post-dose 2 of RIX4414/placebo. Solicited symptoms were collected for eight-days post each dose and safety data was collected throughout the study. Two doses of RIX4414 (Rotarix()) were immunogenic, had a good safety profile and were well-tolerated when administered to healthy Indian infants. ClinicalTrials.gov; NCT00289172; eTrack 103792.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

PubMed

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

PubMed Central

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

PubMed

Piwko, Charles; Prady, Catherine; Yunger, Simon; Pollex, Erika; Moser, Aurelie

2015-08-01

Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

[Safety profile of heterologous serum produced by the Butantan Institute, in São Paulo-SP, Brazil, from 2012 to 2015].

PubMed

Gattás, Vera Lúcia; Braga, Patrícia Emília; Koike, Marcelo Eiji; Lucchesi, Maria Beatriz; Precioso, Alexander Roberto

2017-01-01

to describe the safety profile of the heterologous serum produced by the Butantan Institute (BI) of São Paulo-SP, Brazil. a descriptive study of adverse events (AEs) post-exposure to serum produced by the BI, encoded in the medical terminology of the Medical Dictionary for Regulatory Activities (MedDRA), and spontaneously reported to BI from 2012 to 2015. 52 individuals reported AEs, mainly related to Bothrops antivenom (n=11), diphtheria antitoxin (n=9) and unspecified snakebite serum (n=9); a mean of 3.2 AEs per individual was observed; among the total of 173 AEs, 63.0% were expected considering that they were described in the package insert; most of them were classified as skin and subcutaneous tissue disorders (30.6%); there were six deaths temporally related to the use of serum, but this association was discarded. in the studied period, the serum produced by the BI had no changes in their safety profiles, considering that the AEs were expected, according to the information previously described in the package insert.

Anti-IL-23 Phase II Data for Psoriasis: A Review.

PubMed

Beroukhim, Kourosh; Danesh, Melissa J; Nguyen, Catherine; Austin, Annemieke; Koo, John; Levin, Ethan

2015-10-01

Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23. We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent. By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache. The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

PubMed Central

2016-01-01

Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience

PubMed Central

Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

2014-01-01

Purpose To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). Methods We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008–2010). Results Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain–Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Conclusion Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit–risk profile in adolescent girls and women. PMID:24644078

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

PubMed

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

PubMed Central

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

An examination of the impact of five grade crossing safety factors on driver decision making

DOT National Transportation Integrated Search

2014-04-01

The authors applied signal detection theory to model the impact : of five grade-crossing safety factors to understand their impact : on driver decision making. The safety factors were improving : commercial motor vehicle (CMV) driver safety through f...

Safety, pharmacokinetics, and pharmacodynamics of RSLV-132, an RNase-Fc fusion protein in systemic lupus erythematosus: a randomized, double-blind, placebo-controlled study.

PubMed

Burge, D J; Eisenman, J; Byrnes-Blake, K; Smolak, P; Lau, K; Cohen, S B; Kivitz, A J; Levin, R; Martin, R W; Sherrer, Y; Posada, J A

2017-07-01

Blood-borne RNA circulating in association with autoantibodies is a potent stimulator of interferon production and immune system activation. RSLV-132 is a novel fully human biologic Fc fusion protein that is comprised of human RNase fused to the Fc domain of human IgG1. The drug is designed to remain in circulation and digest extracellular RNA with the aim of preventing activation of the immune system via Toll-like receptors and the interferon pathway. The present study describes the first clinical study of nuclease therapy in 32 subjects with systemic lupus erythematosus. The drug was well tolerated with a very favorable safety profile. The approximately 19-day serum half-life potentially supports once monthly dosing. There were no subjects in the study that developed anti-RSLV-132 antibodies. Decreases in B-cell activating factor correlated with decreases in disease activity in a subset of patients.

[The activity of local health units in agriculture: promotion, prevention, control].

PubMed

Angotzi, G; Ariano, E; Quercia, A

2010-01-01

Agriculture shows an high proportion of injuries, mostly by machineries and instruments, and the highest proportion between fatal and total injuries. The Conference of Regions has adopted the National Agriculture and Forestry Prevention Plan, in application of the "Pact for health and safety in workplaces". The plan gives priority to actions improving the safety of agricultural machines, specially if more frequently involved in serious and fatal injuries. Goal is to achieve an homogenous intervention standard all over in the country, composed by a mix of information, support and control, addressed to farms and agricultural machines traders. Public prevention organizations of Local Health Units moreover will record homogenously the happen modality of fatal and serious accidents, will collaborate in joining prevention objectives with Rural Develop Plans and in drawing up good practices. At another level in some regions have been developed prevention activities for other risk factors: definition of exposition profiles of pesticides, development of professionally exposed workers formation, control of buildings and cattle breeding, medical and epidemiological periodic survey of employees.

Safety and efficacy of intravitreal bevacizumab followed by pegaptanib maintenance as a treatment regimen for age-related macular degeneration.

PubMed

Hughes, Mark S; Sang, Delia N

2006-01-01

Vascular endothelial growth factor (VEGF)-A, both necessary and sufficient in promoting ocular neovascularization, is an attractive therapeutic target. Combining nonselective and selective VEGF blockade may provide clinical benefit with minimal risks in the treatment of neovascular age-related macular degeneration (AMD). Twenty patients with all subtypes of neovascular AMD and a broad range of baseline vision were treated with intravitreal bevacizumab followed by pegaptanib sodium for 54 weeks. Visual acuity measurements, biomicroscopy, funduscopy, fluorescein angiography, optical coherence tomography, and adverse event assessments were performed. Mean visual acuity improved from approximately 20/200 at baseline to 20/80. All patients experienced an improvement in retinal thickness, ranging from -47 to -297 microns. Adverse events were limited to transient irritation or redness. No significant elevation in intraocular pressure occurred following either bevacizumab or pegaptanib injections. Nonselective VEGF blockade with bevacizumab induction and selective VEGF165 blockade with pegaptanib as maintenance therapies may offer clinically meaningful outcomes with acceptable safety profiles in patients with AMD.

Emerging treatments for postmenopausal osteoporosis – focus on denosumab

PubMed Central

Geusens, Piet

2009-01-01

The pathway of the receptor activator of the nuclear factor κB ligand (RANKL), RANK and osteoprotegerin (OPG) plays a central role in coupling bone formation and resorption during normal bone turnover and in a wide spectrum of diseases characterized by disturbed bone remodeling, increased bone resorption and bone destruction (osteoporosis, Paget’s disease of bone, rheumatoid arthritis [RA], metastatic bone disease). Clinical trials indicate that denosumab, a RANKL-specific recombinant humanized monoclonal antibody, is effective in suppressing bone resorption, resulting in increase in bone mineral density (BMD) in post-menopausal women with low BMD, and has the potential to prevent progression of erosions in RA and of skeletal-related events in metastatic bone disease. The effects on fracture reduction in postmenopausal osteoporosis are awaited from the recently finished FREEDOM study. In clinical trials with denosumab, overall adverse events were similar to placebo or comparators, indicating a favorable safety profile in these diseases, which until now have been available up to 4 years, but data on long-term safety will be needed. PMID:19554095

Active SMS-based influenza vaccine safety surveillance in Australian children.

PubMed

Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

2017-12-18

Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6-71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling the factors affecting unsafe behavior in the construction industry from safety supervisors' perspective.

PubMed

Khosravi, Yahya; Asilian-Mahabadi, Hassan; Hajizadeh, Ebrahim; Hassanzadeh-Rangi, Narmin; Bastani, Hamid; Khavanin, Ali; Mortazavi, Seyed Bagher

2014-01-01

There can be little doubt that the construction is the most hazardous industry in the worldwide. This study was designed to modeling the factors affecting unsafe behavior from the perspective of safety supervisors. The qualitative research was conducted to extract a conceptual model. A structural model was then developed based on a questionnaire survey (n=266) by two stage Structural Equation Model (SEM) approach. An excellent confirmed 12-factors structure explained about 62% of variances unsafe behavior in the construction industry. A good fit structural model indicated that safety climate factors were positively correlated with safety individual factors (P<0.001) and workplace safety condition (P<0.001). The workplace safety condition was found to play a strong mediating role in linking the safety climate and construction workers' engagement in safe or unsafe behavior. In order to improve construction safety performance, more focus on the workplace condition is required.

Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure

PubMed Central

Mease, P; Deodhar, A; Fleischmann, R; Wollenhaupt, J; Gladman, D; Leszczyński, P; Vitek, P; Turkiewicz, A; Khraishi, M; FitzGerald, O; Landewé, R; de Longueville, M; Hoepken, B; Peterson, L; van der Heijde, D

2015-01-01

Objective Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. Methods RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. Results Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. Conclusions CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. Trial registration number NCT01087788. PMID:26509074

Interrelation Between Safety Factors and Reliability

NASA Technical Reports Server (NTRS)

Elishakoff, Isaac; Chamis, Christos C. (Technical Monitor)

2001-01-01

An evaluation was performed to establish relationships between safety factors and reliability relationships. Results obtained show that the use of the safety factor is not contradictory to the employment of the probabilistic methods. In many cases the safety factors can be directly expressed by the required reliability levels. However, there is a major difference that must be emphasized: whereas the safety factors are allocated in an ad hoc manner, the probabilistic approach offers a unified mathematical framework. The establishment of the interrelation between the concepts opens an avenue to specify safety factors based on reliability. In cases where there are several forms of failure, then the allocation of safety factors should he based on having the same reliability associated with each failure mode. This immediately suggests that by the probabilistic methods the existing over-design or under-design can be eliminated. The report includes three parts: Part 1-Random Actual Stress and Deterministic Yield Stress; Part 2-Deterministic Actual Stress and Random Yield Stress; Part 3-Both Actual Stress and Yield Stress Are Random.

Lower hybrid current drive in experiments for transport barriers at high βN of JET (Joint European Torus)

NASA Astrophysics Data System (ADS)

Cesario, R. C.; Castaldo, C.; Fonseca, A.; De Angelis, R.; Parail, V.; Smeulders, P.; Beurskens, M.; Brix, M.; Calabrò, G.; De Vries, P.; Mailloux, J.; Pericoli, V.; Ravera, G.; Zagorski, R.

2007-09-01

LHCD has been used in JET experiments aimed at producing internal transport barriers (ITBs) in highly triangular plasmas (δ≈0.4) at high βN (up to 3) for steady-state application. The LHCD is a potentially valuable tool for (i) modifying the target q-profile, which can help avoid deleterious MHD modes and favour the formation of ITBs, and (ii) contributing to the non-inductive current drive required to prolong such plasma regimes. The q-profile evolution has been simulated during the current ramp-up phase for such a discharge (B0 = 2.3 T, IP = 1.5 MA) where 2 MW of LHCD has been coupled. The JETTO code was used taking measured plasma profiles, and the LHCD profile modeled by the LHstar code. The results are in agreement with MSE measurements and indicate the importance of the elevated electron temperature due to LHCD, as well as the driven current. During main heating with 18 MW of NBI and 3 MW of ICRH the bootstrap current density at the edge also becomes large, consistently with the observed reduction of the local turbulence and of the MHD activity. JETTO modelling suggests that the bootstrap current can reduce the magnetic shear (sh) at large radius, potentially affecting the MHD stability and turbulence behaviour in this region. Keywords: lower hybrid current drive (LHCD), bootstrap current, q (safety factor) and shear (sh) profile evolutions.

[Safety profile of dolutegravir].

PubMed

Rivero, Antonio; Domingo, Pere

2015-03-01

Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Applying principles from safety science to improve child protection.

PubMed

Cull, Michael J; Rzepnicki, Tina L; O'Day, Kathryn; Epstein, Richard A

2013-01-01

Child Protective Services Agencies (CPSAs) share many characteristics with other organizations operating in high-risk, high-profile industries. Over the past 50 years, industries as diverse as aviation, nuclear power, and healthcare have applied principles from safety science to improve practice. The current paper describes the rationale, characteristics, and challenges of applying concepts from the safety culture literature to CPSAs. Preliminary efforts to apply key principles aimed at improving child safety and well-being in two states are also presented.

Quantitative evolutionary design

PubMed Central

Diamond, Jared

2002-01-01

The field of quantitative evolutionary design uses evolutionary reasoning (in terms of natural selection and ultimate causation) to understand the magnitudes of biological reserve capacities, i.e. excesses of capacities over natural loads. Ratios of capacities to loads, defined as safety factors, fall in the range 1.2-10 for most engineered and biological components, even though engineered safety factors are specified intentionally by humans while biological safety factors arise through natural selection. Familiar examples of engineered safety factors include those of buildings, bridges and elevators (lifts), while biological examples include factors of bones and other structural elements, of enzymes and transporters, and of organ metabolic performances. Safety factors serve to minimize the overlap zone (resulting in performance failure) between the low tail of capacity distributions and the high tail of load distributions. Safety factors increase with coefficients of variation of load and capacity, with capacity deterioration with time, and with cost of failure, and decrease with costs of initial construction, maintenance, operation, and opportunity. Adaptive regulation of many biological systems involves capacity increases with increasing load; several quantitative examples suggest sublinear increases, such that safety factors decrease towards 1.0. Unsolved questions include safety factors of series systems, parallel or branched pathways, elements with multiple functions, enzyme reaction chains, and equilibrium enzymes. The modest sizes of safety factors imply the existence of costs that penalize excess capacities. Those costs are likely to involve wasted energy or space for large or expensive components, but opportunity costs of wasted space at the molecular level for minor components. PMID:12122135

Safety in the skies : personnel and parties in NTSB aviation accident investigations : master volume

DOT National Transportation Integrated Search

2001-01-01

Recent high-profile commercial aviation mishaps have stretched the National Transportation Safety Board's (NTSB) resources to the limit and are testing the agency's ability to unravel the sorts of complex failures that lead to tragic accidents. In re...

The safety profile of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY).

PubMed

Rinderknecht, Stephen; Bryant, Kristina; Nolan, Terry; Pavia-Ruz, Noris; Doniz, Carlos Aranza; Weber, Miguel Angel Rodriguez; Cohen, Christopher; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M

2012-03-01

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12-15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens. These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies).

[A new method for safety monitoring of natural dietary supplements--quality profile].

PubMed

Wang, Juan; Wang, Li-Ping; Yang, Da-Jin; Chen, Bo

2008-07-01

A new method for safety monitoring of natural dietary supplements--quality profile was proposed. It would convert passive monitoring of synthetic drug to active, and guarantee the security of natural dietary supplements. Preliminary research on quality profile was completed by high performance liquid chromatography (HPLC) and mass spectrometry (MS). HPLC was employed to analyze chemical constituent profiles of natural dietary supplements. The separation was completed on C18 column with acetonitrile and water (0.05% H3PO4) as mobile phase, the detection wavelength was 223 nm. Based on HPLC, stability of quality profile had been studied, and abnormal compounds in quality profile had been analyzed after addition of phenolphthalein, sibutramine, rosiglitazone, glibenclamide and gliclazide. And by MS, detector worked with ESI +, capillary voltage: 3.5 kV, cone voltage: 30 V, extractor voltage: 4 V, RF lens voltage: 0.5 V, source temperature: 105 degrees C, desolvation temperature: 300 degrees C, desolvation gas flow rate: 260 L/h, cone gas flow rate: 50 L/h, full scan mass spectra: m/z 100-600. Abnormal compound in quality profile had been analyzed after addition of N-mono-desmethyl sibutramine. Quality profile based on HPLC had good stability (Similarity > 0.877). Addition of phenolphthalein, sibutramine, rosiglitazone, glibenclamide and gliclazide in natural dietary supplements could be reflected by HPLC, and addition of N-mono-desmethyl sibutramine in natural dietary supplements could be reflected by MS. Quality profile might monitor adulteration of natural dietary supplements, and prevent addition of synthetic drug after "approval".

Quick reference guide to apixaban.

PubMed

Hurst, Katherine Victoria; O'Callaghan, John Matthew; Handa, Ashok

2017-01-01

Direct oral anticoagulants (DOACs) are being increasingly used in the clinical setting for patients at risk of venous thromboembolism (VTE) and/or stroke. These medications offer valued benefits for long-term use, including a fast onset of anticoagulation, fixed anticoagulation profile (and consequent prescription of specified doses) and no requirement for routine monitoring. Apixaban is a selective factor Xa inhibitor, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of acute VTE. Like many of the DOACs, it has a fast onset of action and works to deliver predictable coagulation results. Multiple randomized controlled trials including ARISTOTLE and AMPLIFY have shown apixaban to be noninferior to vitamin K antagonists in the prevention of stroke and VTE, with a good safety profile. This article aims to review the use of apixaban for the prevention and treatment of thromboembolic disease, highlighting the key study results that have led to its current licensing and use.

Quick reference guide to apixaban

PubMed Central

Hurst, Katherine Victoria; O’Callaghan, John Matthew; Handa, Ashok

2017-01-01

Direct oral anticoagulants (DOACs) are being increasingly used in the clinical setting for patients at risk of venous thromboembolism (VTE) and/or stroke. These medications offer valued benefits for long-term use, including a fast onset of anticoagulation, fixed anticoagulation profile (and consequent prescription of specified doses) and no requirement for routine monitoring. Apixaban is a selective factor Xa inhibitor, approved for use in the prevention of stroke in patients with nonvalvular atrial fibrillation and in the prevention and treatment of acute VTE. Like many of the DOACs, it has a fast onset of action and works to deliver predictable coagulation results. Multiple randomized controlled trials including ARISTOTLE and AMPLIFY have shown apixaban to be noninferior to vitamin K antagonists in the prevention of stroke and VTE, with a good safety profile. This article aims to review the use of apixaban for the prevention and treatment of thromboembolic disease, highlighting the key study results that have led to its current licensing and use. PMID:28744136

Current profile redistribution driven by neutral beam injection in a reversed-field pinch

NASA Astrophysics Data System (ADS)

Parke, E.; Anderson, J. K.; Brower, D. L.; Den Hartog, D. J.; Ding, W. X.; Johnson, C. A.; Lin, L.

2016-05-01

Neutral beam injection in reversed-field pinch (RFP) plasmas on the Madison Symmetric Torus [Dexter et al., Fusion Sci. Technol. 19, 131 (1991)] drives current redistribution with increased on-axis current density but negligible net current drive. Internal fluctuations correlated with tearing modes are observed on multiple diagnostics; the behavior of tearing mode correlated structures is consistent with flattening of the safety factor profile. The first application of a parametrized model for island flattening to temperature fluctuations in an RFP allows inferrence of rational surface locations for multiple tearing modes. The m = 1, n = 6 mode is observed to shift inward by 1.1 ± 0.6 cm with neutral beam injection. Tearing mode rational surface measurements provide a strong constraint for equilibrium reconstruction, with an estimated reduction of q0 by 5% and an increase in on-axis current density of 8% ± 5%. The inferred on-axis current drive is consistent with estimates of fast ion density using TRANSP [Goldston et al., J. Comput. Phys. 43, 61 (1981)].

Trenonacog alfa for prophylaxis, on-demand and perioperative management of hemophilia B.

PubMed

Brennan, Yvonne; Curnow, Jennifer; Favaloro, Emmanuel J

2018-01-01

Current treatment for hemophilia B involves replacing the missing coagulation factor IX (FIX) with either plasma-derived or recombinant (r) FIX. Trenonacog alfa is the third normal half-life rFIX that has been granted FDA approval. Area covered: In this review, the authors examine trenonacog alfa for the treatment of hemophilia B including prophylaxis, on-demand and perioperative hemostasis. They compare the PK profile to nonacog alfa and evaluate the drug's efficacy and safety from published studies. Expert opinion: Trenonacog alfa appears to be an effective and safe treatment option for patients with hemophilia B with a PK profile similar to that of nonacog alfa. Despite the advent of extended half-life rFIX and other novel therapeutic approaches, normal half-life rFIX products, including trenonacog alfa, are likely to continue to have a place in hemophilia B treatment for at least the immediate future while the new landscape takes shape, particularly in countries that cannot afford the newer treatments.

Measuring safety climate in elderly homes.

PubMed

Yeung, Koon-Chuen; Chan, Charles C

2012-02-01

Provision of a valid and reliable safety climate dimension brings enormous benefits to the elderly home sector. The aim of the present study was to make use of the safety climate instrument developed by OSHC to measure the safety perceptions of employees in elderly homes such that the factor structure of the safety climate dimensions of elderly homes could be explored. In 2010, surveys by mustering on site method were administered in 27 elderly homes that had participated in the "Hong Kong Safe and Healthy Residential Care Home Accreditation Scheme" organized by the Occupational Safety and Health Council. Six hundred and fifty-one surveys were returned with a response rate of 54.3%. To examine the factor structure of safety climate dimensions in our study, an exploratory factor analysis (EFA) using principal components analysis method was conducted to identify the underlying factors. The results of the modified seven-factor's safety climate structure extracted from 35 items better reflected the safety climate dimensions of elderly homes. The Cronbach alpha range for this study (0.655 to 0.851) indicated good internal consistency among the seven-factor structure. Responses from managerial level, supervisory and professional level, and front-line staff were analyzed to come up with the suggestion on effective ways of improving the safety culture of elderly homes. The overall results showed that managers generally gave positive responses in the factors evaluated, such as "management commitment and concern to safety," "perception of work risks and some contributory influences," "safety communication and awareness," and "safe working attitude and participation." Supervisors / professionals, and frontline level staff on the other hand, have less positive responses. The result of the lowest score in the factors - "perception of safety rules and procedures" underlined the importance of the relevance and practicability of safety rules and procedures. The modified OSHC safety climate tool provided better evidence of structural validity and reliability for use by elderly homes' decision makers as an indicator of employee perception of safety in their institution. The findings and suggestions in the study provide useful information for the management, supervisors/professionals and frontline level staff to cultivate the safety culture in the elderly home sector. Most important, elderly homes can use the modified safety climate scale to identify problem areas in their safety culture and safety management practices and then target these for intervention. Copyright © 2012 Elsevier Ltd. All rights reserved.

75 FR 3784 - Safety Advisory 2009-03

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-22

... prevalence of crossings with substandard vertical profiles, FRA intends to address this issue during the... that utilizes LIDAR (light detection and ranging) mounted on a track inspection vehicle to determine if... transportation officials to identify crossings with substandard vertical profiles and close or take appropriate...

Developing patient safety in dentistry.

PubMed

Pemberton, M N

2014-10-01

Patient safety has always been important and is a source of public concern. Recent high profile scandals and subsequent reports, such as the Francis report into the failings at Mid Staffordshire, have raised those concerns even higher. Mortality and significant morbidity associated with the practice of medicine has led to many strategies to help improve patient safety, however, with its lack of associated mortality and lower associated morbidity, dentistry has been slower at systematically considering how patient safety can be improved. Recently, several organisations, researchers and clinicians have discussed the need for a patient safety culture in dentistry. Strategies are available to help improve patient safety in healthcare and deserve further consideration in dentistry.

Dimensions of Safety Climate among Iranian Nurses.

PubMed

Konjin, Z Naghavi; Shokoohi, Y; Zarei, F; Rahimzadeh, M; Sarsangi, V

2015-10-01

Workplace safety has been a concern of workers and managers for decades. Measuring safety climate is crucial in improving safety performance. It is also a method of benchmarking safety perception. To develop and validate a psychometrics scale for measuring nurses' safety climate. Literature review, subject matter experts and nurse's judgment were used in items developing. Content validity and reliability for new tool were tested by content validity index (CVI) and test-retest analysis, respectively. Exploratory factor analysis (EFA) with varimax rotation was used to improve the interpretation of latent factors. A 40-item scale in 6 factors was developed, which could explain 55% of the observed variance. The 6 factors included employees' involvement in safety and management support, compliance with safety rules, safety training and accessibility to personal protective equipment, hindrance to safe work, safety communication and job pressure, and individual risk perception. The proposed scale can be used in identifying the needed areas to implement interventions in safety climate of nurses.

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

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

Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com; Nolte, Marc W.; Solomon, Cristina

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii)more » the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated, with no adverse events. • Overall, human fibrinogen concentrate demonstrated a good safety profile. • This data adds to the safety information available to date on this hemostatic agent.« less

Safety leadership in the teaching laboratories of electrical and electronic engineering departments at Taiwanese Universities.

PubMed

Wu, Tsung-Chih

2008-01-01

Safety has always been one of the principal goals in teaching laboratories. Laboratories cannot serve their educational purpose when accidents occur. The leadership of department heads has a major impact on laboratory safety, so this study discusses the factors affecting safety leadership in teaching laboratories. This study uses a mail survey to explore the perceived safety leadership in electrical and electronic engineering departments at Taiwanese universities. An exploratory factor analysis shows that there are three main components of safety leadership, as measured on a safety leadership scale: safety controlling, safety coaching, and safety caring. The descriptive statistics also reveals that among faculty, the perception of department heads' safety leadership is in general positive. A two-way MANOVA shows that there are interaction effects on safety leadership between university size and instructor age; there are also interaction effects between presence of a safety committee and faculty gender and faculty age. It is therefore necessary to assess organizational factors when determining whether individual factors are the cause of differing perceptions among faculty members. The author also presents advice on improving safety leadership for department heads at small universities and at universities without safety committees.

76 FR 35130 - Pipeline Safety: Control Room Management/Human Factors

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration 49 CFR Parts...: Control Room Management/Human Factors AGENCY: Pipeline and Hazardous Materials Safety Administration... safety standards, risk assessments, and safety policies for natural gas pipelines and for hazardous...

A firm size and safety performance profile of the U.S. motor carrier industry : [executive summary].

DOT National Transportation Integrated Search

2015-11-01

Motor carrier crashes continue to present a societal and public policy : problem. Large commercial truck crashes are a topic of serious concern : in Iowa. Statistics illustrate the need to make further progress on the : safety performance of motor ca...

Carpentry and Finishing Procedures. Building Maintenance. Module II. Instructor's Guide.

ERIC Educational Resources Information Center

Hawk, Sam; Brunk, Art

This curriculum guide, keyed to the building maintenance competency profile developed by industry and education professionals, provides three units on carpentry and finishing procedures. The first unit, Exterior Carpentry, contains the following lessons: carpentry safety procedures, ladder and scaffolding safety, door installation/repair,…

Study on the creation and destruction of transport barriers via the effective safety factors for energetic particles

NASA Astrophysics Data System (ADS)

Ogawa, Shun; Leoncini, Xavier; Dif-Pradalier, Guilhem; Garbet, Xavier

2016-12-01

Charged particles with low kinetic energy move along the magnetic field lines, but so do not the energetic particles. We investigate the topological structure changes in the phase space of energetic particles with respect to the magnetic one. For this study, cylindrical magnetic fields with non-monotonic safety factors that induce the magnetic internal transport barrier are considered. We show that the topological structure of the magnetic field line and of the particle trajectories can be quite different. We explain this difference using the concept of an effective particle q-profile. Using this notion, we can investigate the location and existence of resonances for particle orbits that are different from the magnetic ones. These are examined both numerically by integrating an equation of motion and theoretically by the use of Alfvén's guiding center theory and by the use of an effective reduced Hamiltonian for the integrable unperturbed system. It is clarified that, for the energetic particles, the grad B drift effect shifts the resonances and the drift induced by curvature of the magnetic field line leads to the vanishing of the resonances. As a result, we give two different mechanisms that lead to the creation of transport barriers for energetic particles in the region where the magnetic field line is chaotic.

[Stress in auto-transportation sector between prejudice and reality].

PubMed

Ferranti, A; Spada, S; Mosconi, G

2009-01-01

Every year in the EU about 800 drivers die in road accidents. In Italy the average is around 200 deaths per year. Based on this context the Occupational Medicine Department (OMD) of Bergamo Hospital has sponsored a new project dedicated to the healthcare and safety of all employees of road haulage in the province of Bergamo. Furthermore the collaboration between UMD and the Clinical Psychology Department of the hospital has allowed the fulfillment of another project aiming to evaluate the personality profile of around 80 drivers employed in the road haulage sector". The aims of the projects is to identify and to point out dangerous situations of significant psychological vulnerability; to know the current situation and to discriminate stress factors from protective ones; to make companies more aware of prevention activities; to inform the drivers about their companies' policy in order to grant safety in their job. The psychological tools used were: half open interview and Personality Inventory MMPI2. The population was selected randomly from volunteers. Now we know the results in 33 tested drivers. So far seven cases have been classified as psychological vulnerable and stress and protective factors have been identified. Results underline the relevance of an integrated approach able to take care of the employees and involving the companies in the prevention programs.

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

PubMed

Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

2005-01-01

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance.

PubMed

Mathieu, Chantal; Kozlovski, Plamen; Paldánius, Päivi M; Foley, James E; Modgill, Vikas; Evans, Marc; Serban, Carmen

2017-08-01

Vildagliptin is one of the most extensively studied dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of its clinical utility. Over the last decade, a vast panorama of evidence on the benefit-risk profile of vildagliptin has been generated in patients with type 2 diabetes mellitus (T2DM). In this article, we review the cumulative evidence on the safety of vildagliptin from the clinical development programme, as well as reports of rare adverse drug reactions detected during the post-marketing surveillance of the drug. Across clinical studies, the overall safety and tolerability profile of vildagliptin was similar to placebo, and it was supported by real-world data in a broad population of patients with T2DM, making DPP-4 inhibitors, like vildagliptin, a safe option for managing patients with T2DM.

Modeling Techniques for Shipboard Manning: A Review and Plan for Development

DTIC Science & Technology

1993-02-01

manning levels. Once manning models have been created, experiments can be conducted to show how changes in the manning structure might affect ship safety...these predictions, users of the manning models can evaluate how changes in crew configurations, manning levels, and voyage profiles affect ship safety...mitigate emergency situations would provide crucial information on how changes in manning structure would affect overall ship safety. Like emergency

Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3)

PubMed Central

Bartlett, Cynthia Huang; Schnell, Patrick; DeMichele, Angela M.; Loi, Sherene; Ro, Jungsil; Colleoni, Marco; Iwata, Hiroji; Harbeck, Nadia; Cristofanilli, Massimo; Zhang, Ke; Thiele, Alexandra; Turner, Nicholas C.; Rugo, Hope S.

2016-01-01

Background. Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib’s safety profile to effectively manage toxicity and optimize clinical benefit. Materials and Methods. Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. Results. A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3–4 neutropenia with palbociclib. Dose modifications for grade 3–4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1–2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. Conclusion. Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. Implications for Practice: Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed mechanism of action, palbociclib-related neutropenia differs in its clinical time course, patterns, and consequences from those seen with chemotherapy. Neutropenia can be effectively managed by a dose reduction, interruption, or cycle delay without compromising efficacy. A significant efficacy gain and a favorable safety profile support the consideration of incorporating palbociclib into the routine management of HR-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. PMID:27368881

Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3).

PubMed

Verma, Sunil; Bartlett, Cynthia Huang; Schnell, Patrick; DeMichele, Angela M; Loi, Sherene; Ro, Jungsil; Colleoni, Marco; Iwata, Hiroji; Harbeck, Nadia; Cristofanilli, Massimo; Zhang, Ke; Thiele, Alexandra; Turner, Nicholas C; Rugo, Hope S

2016-10-01

Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (<1%) patients. The percentage of grade 1-2 infections was higher than in the placebo arm. Grade 1 stomatitis occurred in 8% of patients. Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed mechanism of action, palbociclib-related neutropenia differs in its clinical time course, patterns, and consequences from those seen with chemotherapy. Neutropenia can be effectively managed by a dose reduction, interruption, or cycle delay without compromising efficacy. A significant efficacy gain and a favorable safety profile support the consideration of incorporating palbociclib into the routine management of HR-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. ©AlphaMed Press.

Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

PubMed

Humbert, M; Segal, E S; Kiely, D G; Carlsen, J; Schwierin, B; Hoeper, M M

2007-08-01

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.

Continuing Education in Patient Safety: Massive Open Online Courses as a New Training Tool.

PubMed

Sarabia-Cobo, Carmen María; Torres-Manrique, Blanca; Ortego-Mate, Ma Carmen; Salvadores-Fuentes, Paloma; Sáenz-Jalón, María

2015-10-01

Describe the use of two massive open online courses designed to provide education on patient safety. Review follow-up evaluation data from the courses. DISCLOSURE STATEMENT: Neither the planners nor the authors have any conflicts of interest to disclose. The Nursing School of the University of Cantabria conducted a training session on patient safety through two massive open online courses (MOOCs) aimed at the general population and especially Spanish-speaking health professionals. This study aimed to analyze the profile of health professionals who have completed the courses, their degree of satisfaction, and the percentage of completion. In this retrospective and observational study, two MOOCs on clinical safety were created through an online platform (MiríadaX). Quantitative analysis of the profile of health professionals, their degree of satisfaction, and the percentage of completion was performed. A total of 12,400 students were enrolled, and the average completion rate was 32%. The profile of the average student was female, 37 years old, college educated, a nurse in a hospital, and interested in the course because it may be useful for performing her work. Fifty-five percent of students were very satisfied with the course. MOOCs are considered to be effective and easily accessible, with quality content for professional continuing education that encourages interdisciplinary work and meeting professionals from around the world. Copyright 2015, SLACK Incorporated.

Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

PubMed

Schäfer, Birgit; Holzer, Georg W; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A; Kreil, Thomas R; Barrett, P Noel; Falkner, Falko G

2011-01-01

Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

Information technology in pharmacovigilance: Benefits, challenges, and future directions from industry perspectives.

PubMed

Lu, Zhengwu

2009-01-01

Risk assessment during clinical product development needs to be conducted in a thorough and rigorous manner. However, it is impossible to identify all safety concerns during controlled clinical trials. Once a product is marketed, there is generally a large increase in the number of patients exposed, including those with comorbid conditions and those being treated with concomitant medications. Therefore, postmarketing safety data collection and clinical risk assessment based on observational data are critical for evaluating and characterizing a product's risk profile and for making informed decisions on risk minimization. Information science promises to deliver effective e-clinical or e-health solutions to realize several core benefits: time savings, high quality, cost reductions, and increased efficiencies with safer and more efficacious medicines. The development and use of standard-based pharmacovigilance system with integration connection to electronic medical records, electronic health records, and clinical data management system holds promise as a tool for enabling early drug safety detections, data mining, results interpretation, assisting in safety decision making, and clinical collaborations among clinical partners or different functional groups. The availability of a publicly accessible global safety database updated on a frequent basis would further enhance detection and communication about safety issues. Due to recent high-profile drug safety problems, the pharmaceutical industry is faced with greater regulatory enforcement and increased accountability demands for the protection and welfare of patients. This changing climate requires biopharmaceutical companies to take a more proactive approach in dealing with drug safety and pharmacovigilance.

Determination of Slope Safety Factor with Analytical Solution and Searching Critical Slip Surface with Genetic-Traversal Random Method

PubMed Central

2014-01-01

In the current practice, to determine the safety factor of a slope with two-dimensional circular potential failure surface, one of the searching methods for the critical slip surface is Genetic Algorithm (GA), while the method to calculate the slope safety factor is Fellenius' slices method. However GA needs to be validated with more numeric tests, while Fellenius' slices method is just an approximate method like finite element method. This paper proposed a new method to determine the minimum slope safety factor which is the determination of slope safety factor with analytical solution and searching critical slip surface with Genetic-Traversal Random Method. The analytical solution is more accurate than Fellenius' slices method. The Genetic-Traversal Random Method uses random pick to utilize mutation. A computer automatic search program is developed for the Genetic-Traversal Random Method. After comparison with other methods like slope/w software, results indicate that the Genetic-Traversal Random Search Method can give very low safety factor which is about half of the other methods. However the obtained minimum safety factor with Genetic-Traversal Random Search Method is very close to the lower bound solutions of slope safety factor given by the Ansys software. PMID:24782679

Mode of Action Profiles for Pesticide Compounds with Rodent Liver Tumor Outcomes

EPA Science Inventory

Mode of action (MOA) provides a central framework for assessing human relevance of adverse health outcomes observed in nonclinical safety studies. The goal of this study was to characterize MOA profiles for known rodent liver tumorigens identified from a database of pesticides as...

Light vehicle crash avoidance needs and countermeasure profiles for safety applications based on vehicle-to-vehicle communications

DOT National Transportation Integrated Search

2013-04-30

This report discusses light-vehicle crash countermeasure profiles and functions for five target pre-crash scenario groups based on vehicle-to-vehicle (V2V) communications. Target pre-crash scenario groups include rear-end, lane change, opposite direc...

Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

PubMed

Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2015-02-01

The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fixed combination of repaglinide and metformin in the management of type 2 diabetes

PubMed Central

Moses, Robert

2009-01-01

Treatment to target fasting blood glucose (FBG), postprandial glucose (PPG) and HbA1c are essential in the management of type 2 diabetes to reduce the risk of vascular complications. Early combination therapy with oral agents is increasingly being seen as important to achieve this. Repaglinide, a rapid-acting insulin secretagogue, targets PPG, and metformin, an insulin sensitizer, targets FBG. Because of their complementary modes of action these therapies are frequently given as combination therapy in separate tablets. To overcome the issues with adherence to multiple tablets, repaglinide and metformin are now available in a fixed-dose combination (FDC). Repaglinide/metformin FDC is bioequivalent to each tablet given separately, suggesting that the efficacy and safety profile is similar. There is no effect of food on repaglinide when in the FDC. Repaglinide/metformin FDC is as effective in reducing HbA1c and FBG whether given twice or three times daily, with a similar safety profile. Repaglinide/metformin FDC twice daily is as effective in reducing HbA1c and FBG as rosiglitazone/metformin FDC with a similar safety profile, but unlike the rosiglitazone/metformin FDC, repaglinide/metformin FDC improves the lipid profile. Repaglinide/metformin FDC represents a new option in the pursuit of achieving glucose targets and reducing vascular risk in type 2 diabetes, with the advantage of improving adherence. PMID:21437123

Fixed combination of repaglinide and metformin in the management of type 2 diabetes.

PubMed

Moses, Robert

2009-06-24

Treatment to target fasting blood glucose (FBG), postprandial glucose (PPG) and HbA(1c) are essential in the management of type 2 diabetes to reduce the risk of vascular complications. Early combination therapy with oral agents is increasingly being seen as important to achieve this. Repaglinide, a rapid-acting insulin secretagogue, targets PPG, and metformin, an insulin sensitizer, targets FBG. Because of their complementary modes of action these therapies are frequently given as combination therapy in separate tablets. To overcome the issues with adherence to multiple tablets, repaglinide and metformin are now available in a fixed-dose combination (FDC). Repaglinide/metformin FDC is bioequivalent to each tablet given separately, suggesting that the efficacy and safety profile is similar. There is no effect of food on repaglinide when in the FDC. Repaglinide/metformin FDC is as effective in reducing HbA(1c) and FBG whether given twice or three times daily, with a similar safety profile. Repaglinide/metformin FDC twice daily is as effective in reducing HbA(1c) and FBG as rosiglitazone/metformin FDC with a similar safety profile, but unlike the rosiglitazone/metformin FDC, repaglinide/metformin FDC improves the lipid profile. Repaglinide/metformin FDC represents a new option in the pursuit of achieving glucose targets and reducing vascular risk in type 2 diabetes, with the advantage of improving adherence.

New geometric design consistency model based on operating speed profiles for road safety evaluation.

PubMed

Camacho-Torregrosa, Francisco J; Pérez-Zuriaga, Ana M; Campoy-Ungría, J Manuel; García-García, Alfredo

2013-12-01

To assist in the on-going effort to reduce road fatalities as much as possible, this paper presents a new methodology to evaluate road safety in both the design and redesign stages of two-lane rural highways. This methodology is based on the analysis of road geometric design consistency, a value which will be a surrogate measure of the safety level of the two-lane rural road segment. The consistency model presented in this paper is based on the consideration of continuous operating speed profiles. The models used for their construction were obtained by using an innovative GPS-data collection method that is based on continuous operating speed profiles recorded from individual drivers. This new methodology allowed the researchers to observe the actual behavior of drivers and to develop more accurate operating speed models than was previously possible with spot-speed data collection, thereby enabling a more accurate approximation to the real phenomenon and thus a better consistency measurement. Operating speed profiles were built for 33 Spanish two-lane rural road segments, and several consistency measurements based on the global and local operating speed were checked. The final consistency model takes into account not only the global dispersion of the operating speed, but also some indexes that consider both local speed decelerations and speeds over posted speeds as well. For the development of the consistency model, the crash frequency for each study site was considered, which allowed estimating the number of crashes on a road segment by means of the calculation of its geometric design consistency. Consequently, the presented consistency evaluation method is a promising innovative tool that can be used as a surrogate measure to estimate the safety of a road segment. Copyright © 2012 Elsevier Ltd. All rights reserved.

2011 Annual Meeting of the Safety Pharmacology Society: an overview.

PubMed

Cavero, Icilio

2012-03-01

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization this information should be complemented by a clear clinical proof of safety. The ongoing outsourcing process of Regulatory Safety Pharmacology activities from large Pharmas to contract research organizations should be taken as an opportunity to establish long-overdue in-house Exploratory Safety Pharmacology units fully dedicated to the optimization of clinical candidates on organ safety.

The Ultimate Factor of Safety for Aircraft and Spacecraft Its History, Applications and Misconceptions

NASA Technical Reports Server (NTRS)

Zipay, John J.; Modlin, C. Thomas, Jr.; Larsen, Curtis E.

2016-01-01

The ultimate factor of safety (FOSULT) concept used in aircraft and spacecraft has evolved over many decades. Currently an FOSULT 1.5 is the FAR-mandated value for aircraft while an FOSULT of 1.4 has been used in various spacecraft. This paper was motivated by the desire to concisely explain the origins, proper interpretation and application of the ultimate factor of safety concept, since the authors have seen throughout their careers many misconceptions and incorrect applications of this concept. The history of the ultimate factor of safety concept is briefly summarized, the proper application of the factor of safety in aircraft design, structural analysis and operations is covered in detail, examples of limit load exceedance in aircraft and spacecraft are discussed, the evolution of the 1.4 FOSULT for spacecraft is described and some misconceptions regarding the ultimate factor of safety concept are addressed. It is hoped that this paper can be a summary resource for engineers to understand the origin, purpose and proper application of the ultimate factor of safety.

Predicting safety culture: the roles of employer, operations manager and safety professional.

PubMed

Wu, Tsung-Chih; Lin, Chia-Hung; Shiau, Sen-Yu

2010-10-01

This study explores predictive factors in safety culture. In 2008, a sample 939 employees was drawn from 22 departments of a telecoms firm in five regions in central Taiwan. The sample completed a questionnaire containing four scales: the employer safety leadership scale, the operations manager safety leadership scale, the safety professional safety leadership scale, and the safety culture scale. The sample was then randomly split into two subsamples. One subsample was used for measures development, one for the empirical study. A stepwise regression analysis found four factors with a significant impact on safety culture (R²=0.337): safety informing by operations managers; safety caring by employers; and safety coordination and safety regulation by safety professionals. Safety informing by operations managers (ß=0.213) was by far the most significant predictive factor. The findings of this study provide a framework for promoting a positive safety culture at the group level. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Optimizing outcomes with polymethylmethacrylate fillers.

PubMed

Gold, Michael H; Sadick, Neil S

2018-06-01

The ideal filler should be long-lasting, biocompatible, chemically inert, soft and easy to use, and have a long history of safety. This review focuses on the evolution and development of the PMMA-collagen gel, Bellafill, and the 10 years of postmarketing experience of Bellafill since it received premarket approval (PMA) from the FDA as Artefill in 2006. Artefill was rebranded to Bellafill in 2015. The authors conducted a literature search on PubMed for key articles describing the steps in which Arteplast, a PMMA filler developed in 1989, led to the development of Bellafill, the only PMMA filler approved by the US FDA for the treatment of nasolabial folds and acne scar correction. The factors governing efficacy and safety were also evaluated for the major PMMA fillers available in the world. The process of manufacturing and purifying PMMA has played a major role in minimizing adverse events for Bellafill. Postmarketing surveillance data for the 2007-2016 period show that for more than 530 000 Bellafill syringes distributed worldwide, 11 confirmed granulomas (excluding clinical trial data) (0.002% of syringes sold) have been reported. Data on other PMMA fillers are limited and inconsistent. The authors suggest that adverse events are often attributable to lack of proficiency in treatment technique and other factors. Bellafill has demonstrated an excellent safety and effectiveness profile in multiple clinical studies, customer feedback, and 10 years of postmarketing surveillance experience. Adverse events occur with all fillers for a variety of reasons. In addition to quality of the product, injector skill and technique are critical to ensuring good clinical outcomes. © 2018 Wiley Periodicals, Inc.

Development and initial validation of an Aviation Safety Climate Scale.

PubMed

Evans, Bronwyn; Glendon, A Ian; Creed, Peter A

2007-01-01

A need was identified for a consistent set of safety climate factors to provide a basis for aviation industry benchmarking. Six broad safety climate themes were identified from the literature and consultations with industry safety experts. Items representing each of the themes were prepared and administered to 940 Australian commercial pilots. Data from half of the sample (N=468) were used in an exploratory factor analysis that produced a 3-factor model of Management commitment and communication, Safety training and equipment, and Maintenance. A confirmatory factor analysis on the remaining half of the sample showed the 3-factor model to be an adequate fit to the data. The results of this study have produced a scale of safety climate for aviation that is both reliable and valid. This study developed a tool to assess the level of perceived safety climate, specifically of pilots, but may also, with minor modifications, be used to assess other groups' perceptions of safety climate.

Effect of particle pinch on the fusion performance and profile features of an international thermonuclear experimental reactor-like fusion reactor

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

Wang, Shijia, E-mail: wangsg@mail.ustc.edu.cn; Wang, Shaojie

2015-04-15

The evolution of the plasma temperature and density in an international thermonuclear experimental reactor (ITER)-like fusion device has been studied by numerically solving the energy transport equation coupled with the particle transport equation. The effect of particle pinch, which depends on the magnetic curvature and the safety factor, has been taken into account. The plasma is primarily heated by the alpha particles which are produced by the deuterium-tritium fusion reactions. A semi-empirical method, which adopts the ITERH-98P(y,2) scaling law, has been used to evaluate the transport coefficients. The fusion performances (the fusion energy gain factor, Q) similar to the ITERmore » inductive scenario and non-inductive scenario (with reversed magnetic shear) are obtained. It is shown that the particle pinch has significant effects on the fusion performance and profiles of a fusion reactor. When the volume-averaged density is fixed, particle pinch can lower the pedestal density by ∼30%, with the Q value and the central pressure almost unchanged. When the particle source or the pedestal density is fixed, the particle pinch can significantly enhance the Q value by  60%, with the central pressure also significantly raised.« less

High-beta, steady-state hybrid scenario on DIII-D

DOE PAGES

Petty, C. C.; Kinsey, J. E.; Holcomb, C. T.; ...

2015-12-17

Here, the potential of the hybrid scenario (first developed as an advanced inductive scenario for high fluence) as a regime for high-beta, steady-state plasmas is demonstrated on the DIII-D tokamak. These experiments show that the beneficial characteristics of hybrids, namely safety factor ≥1 with low central magnetic shear, high stability limits and excellent confinement, are maintained when strong central current drive (electron cyclotron and neutral beam) is applied to increase the calculated non-inductive fraction to ≈100% (≈50% bootstrap current). The best discharges achieve normalized beta of 3.4, IPB98(y,2) confinement factor of 1.4, surface loop voltage of 0.01 V, and nearlymore » equal electron and ion temperatures at low collisionality. A zero-dimensional physics model shows that steady-state hybrid operation with Q fus ~ 5 is feasible in FDF and ITER. The advantage of the hybrid scenario as an Advanced Tokamak regime is that the external current drive can be deposited near the plasma axis where the efficiency is high; additionally, good alignment between the current drive and plasma current profiles is not necessary as the poloidal magnetic flux pumping self-organizes the current density profile in hybrids with an m/n=3/2 tearing mode.« less

Safety assessment in the urban park environment in Alborz Province, Iran.

PubMed

Oostakhan, Morteza; Babaei, Aliakbar

2013-01-01

Urban parks, as one of the recreational and sports sectors, could cause serious injuries among different ages if the safety issues in their design are not considered. These injuries can result from the equipment in the park, including play and sports equipment, or even from environmental factors, too. Lack of safety benchmark in parks will impact on the development of future proposals. In this article, attempts are made to survey the important safety factors in the urban parks including playgrounds, fitness equipment, pedestrian surface and environmental factors into a risk assessment. Hence, a checklist of safety factors was used. A Yes or No descriptor was allocated to any factor for determining safety level. The study also suggests recommendations for future planning concerning existing failures for designers. It was found that the safety level of the regional and local parks differ from each other.

Students' Perceptions of Safety at School after Sandy Hook

ERIC Educational Resources Information Center

Fisher, Benjamin W.; Nation, Maury; Nixon, Carol T.; McIlroy, Sarah

2017-01-01

High profile school shootings have served as pivotal events for developing policies to promote student safety. Although previous studies indicate that exposure to violence is associated with feeling unsafe at school and poorer academic and psychosocial outcomes, research on the relationship between widely publicized acts of school violence and…

Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies.

PubMed

Fleischmann, Roy; Kremer, Joel; Tanaka, Yoshiya; Gruben, David; Kanik, Keith; Koncz, Tamas; Krishnaswami, Sriram; Wallenstein, Gene; Wilkinson, Bethanie; Zwillich, Samuel H; Keystone, Edward

2016-12-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies. © 2016 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Impact of IgG Fc-Oligosaccharides on Recombinant Monoclonal Antibody Structure, Stability, Safety, and Efficacy.

PubMed

Liu, Hongcheng; Nowak, Christine; Andrien, Bruce; Shao, Mei; Ponniah, Gomathinayagam; Neill, Alyssa

2017-09-01

Glycosylation of the conserved asparagine residue in the CH2 domain is the most common posttranslational modification of recombinant monoclonal antibodies. Ideally, a consistent oligosaccharide profile should be maintained from early clinical material to commercial material for the development of recombinant monoclonal therapeutics, though variation in the profile is a typical result of process changes. The risk of oligosaccharide variation posed to further development is required to be thoroughly evaluated based on its impact on antibody structure, stability, efficacy and safety. The variation should be controlled within a range so that there is no detrimental impact on safety and efficacy and thus allowing the use of early phase safety and efficacy data to support project advancement to later phase. This review article focuses on the current scientific understanding of the commonly observed oligosaccharides found in recombinant monoclonal antibodies and their impact on structure, stability and biological functions, which are the basis to evaluate safety and efficacy. It also provides a brief discussion on critical quality attribute (CQA) assessment with regard to oligosaccharides based on the mechanism of action (MOA). © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1173-1181, 2017. © 2017 American Institute of Chemical Engineers.

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

PubMed

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

School and Community Factors Involved in Chilean Students' Perception of School Safety

ERIC Educational Resources Information Center

López, Verónica; Torres-Vallejos, Javier; Villalobos-Parada, Boris; Gilreath, Tamika D.; Ascorra, Paula; Bilbao, Marian; Morales, Macarena; Carrasco, Claudia

2017-01-01

Identifying and understanding predictors of school safety perceptions is important due to its consequences for students. However, it is not clear what school-related factors most contribute to explaining students' perception of school safety, and how they relate to community-related factors such as neighborhood safety. The purpose of this study…

Sustained high βN plasmas on EAST tokamak

NASA Astrophysics Data System (ADS)

Gao, Xiang; the EAST team

2018-05-01

Sustained high normalized beta (βN ∼ 1.9) plasmas with an ITER-like tungsten divertor have been achieved on EAST tokamak recently. The high power NBI heating system of 4.8 MW and the 4.6 GHz lower hybrid wave of 1 MW were developed and applied to produce edge and internal transport barriers in high βN discharges. The central flat q profile with q (ρ) ∼ 1 at ρ < 0.3 region and edge safety factor q95 = 4.7 is identified by the multi-channel far-infrared laser polarimeter and the EFIT code. The fraction of non-inductive current is about 40%. The relation between fishbone activity and ITB formation is observed and discussed.

Two-point motional Stark effect diagnostic for Madison Symmetric Torus

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

Ko, J.; Den Hartog, D. J.; Caspary, K. J.

2010-10-15

A high-precision spectral motional Stark effect (MSE) diagnostic provides internal magnetic field measurements for Madison Symmetric Torus (MST) plasmas. Currently, MST uses two spatial views - on the magnetic axis and on the midminor (off-axis) radius, the latter added recently. A new analysis scheme has been developed to infer both the pitch angle and the magnitude of the magnetic field from MSE spectra. Systematic errors are reduced by using atomic data from atomic data and analysis structure in the fit. Reconstructed current density and safety factor profiles are more strongly and globally constrained with the addition of the off-axis radiusmore » measurement than with the on-axis one only.« less

Natural Resources. Ohio's Competency Analysis Profile. Forest Industry Worker. Resource Conservation.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

This competency analysis profile lists 155 competencies that have been identified by employers as core competencies for inclusion in programs to train forest industry and resource conservation workers. The core competencies are organized into 10 units dealing the following: general safety precautions, natural resource industry operations, soil…

Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-fixed paraffin-embedded (FFPE) Samples

EPA Science Inventory

Formalin-fixed paraffin-embedded (FFPE) samples provide a vast untapped resource for chemical safety and translational science. To date, genomic profiling of FFPE samples has been limited by poor RNA quality and inconsistent results with limited utility in dose-response assessmen...

Managing risk in healthcare: understanding your safety culture using the Manchester Patient Safety Framework (MaPSaF).

PubMed

Parker, Dianne

2009-03-01

To provide sufficient information about the Manchester Patient Safety Framework (MaPSaF) to allow healthcare professionals to assess its potential usefulness. The assessment of safety culture is an important aspect of risk management, and one in which there is increasing interest among healthcare organizations. Manchester Patient Safety Framework offers a theory-based framework for assessing safety culture, designed specifically for use in the NHS. The framework covers multiple dimensions of safety culture, and five levels of safety culture development. This allows the generation of a profile of an organization's safety culture in terms of areas of relative strength and challenge, which can be used to identify focus issues for change and improvement. Manchester Patient Safety Framework provides a useful method for engaging healthcare professionals in assessing and improving the safety culture in their organization, as part of a programme of risk management.

Enhancing safety and aroma appealing of fresh-cut fruits and vegetables using the antimicrobial and aromatic power of essential oils.

PubMed

Ayala-Zavala, J Fernando; González-Aguilar, Gustavo A; del-Toro-Sánchez, L

2009-09-01

Microbial and aroma attributes are within the most decisive factors limiting safety and sensory appealing of fresh-cut fruits and vegetables. Alternatively, several plant essential oils (EOs) are constituted of several volatile active compounds and most of them present antimicrobial potential and had different aroma profile. Considering these premises, this hypothesis article states that safety and aroma appealing of fresh-cut produce could be improved with EO treatment. EOs could prevent fresh-cut fruit decay; however, their volatile constituents could be sorbed by the produce, and according to the aroma notes of the antimicrobial oil, sensorial appealing of odor, and flavor of the treated produce might be affected positively or negatively. Specifically, garlic oil is a natural antimicrobial constituted by sulfur compounds, which are responsible for its odor and antimicrobial properties. Besides, fresh-cut tomato is a highly perishable product that needs antimicrobial agents to preserve its quality and safety for a longer period of time. From the sensorial point of view, aroma combination of garlic and tomato is a common seasoning practice in Europe and America and well accepted by consumers. Once the right combination of flavors between the EOs and the fresh-cut produce has been selected, safety and quality of the treated fruit could be improved by adding antimicrobial protection and extra aroma. Therefore, other combinations between EOs and fresh-cut produce are discussed. This approximation could reinforce the trends of natural food preservation, accomplishing the demands of the increasing sector of consumers demanding tasty and convenient fresh-cut produce, containing only natural ingredients.

Safety results from a phase III study (TURANDOT trial by CECOG) of first-line bevacizumab in combination with capecitabine or paclitaxel for HER-2-negative locally recurrent or metastatic breast cancer.

PubMed

Lang, I; Inbar, M J; Kahán, Z; Greil, R; Beslija, S; Stemmer, S M; Kaufman, B; Zvirbule, Z; Steger, G G; Messinger, D; Brodowicz, T; Zielinski, C

2012-11-01

We report safety data from a randomised, phase III study (CECOG/BC.1.3.005) evaluating first-line bevacizumab plus paclitaxel or capecitabine for locally recurrent or metastatic breast cancer. Patients aged ≥18 years with human epidermal growth factor receptor-2-negative breast adenocarcinoma were randomised to Arm A: bevacizumab 10 mg/kg days 1 and 15; paclitaxel 90 mg/m(2) days 1, 8, and 15, every 4 weeks; or Arm B: bevacizumab 15 mg/kg day 1; capecitabine 1000 mg/m(2) b.i.d., days 1-14, every 3 weeks, until disease progression, unacceptable toxicity or consent withdrawal. A post hoc interim safety analysis included 561 patients (Arm A: 284, Arm B: 277). The regimens demonstrated similar frequencies of all-grade and serious adverse events (SAEs), but different safety profiles. Treatment-related events occurred in 85.2% (Arm A) and 78.0% (Arm B) of patients. Fatigue was most common in Arm A (30.6% versus 23.5% Arm B), and hand-foot syndrome (HFS) most common in Arm B (49.5% versus 2.5% Arm A). Diarrhoea (Arm A: 0.4%, Arm B: 1.4%) and pulmonary embolism (Arm A: 0.7%, Arm B: 1.1%) were the most frequently reported SAEs. These findings are in-line with safety data for bevacizumab plus paclitaxel or capecitabine, reported in previous phase III trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safety and efficacy evaluation of gelatin-based nanoparticles associated with UV filters.

PubMed

Oliveira, Camila Areias de; Dario, Michelli Ferrera; Sarruf, Fernanda Daud; Mariz, Inês Fátima Afonso; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

2016-04-01

The safety and efficacy assessment of nanomaterials is a major concern of industry and academia. These materials, due to their nanoscale size, can have chemical, physical, and biological properties that differ from those of their larger counterparts. The encapsulation of natural ingredients can provide marked improvements in sun protection efficacy. This strategy promotes solubility enhancement of flavonoids and yields an improved active ingredient with innovative physical, physicochemical and functional characteristics. Rutin, a flavonoid, has chemical and functional stability in topical vehicles exerting a synergistic effect in association with ultraviolet (UV) filters. However, the solubility of rutin is a limiting factor. Additionally, this bioactive compound does not have tendency to permeate across the stratum corneum. As an alternative to common synthetic based sunscreens, rutin-entrapped gelatin nanoparticles were designed. The present study investigated the pre-clinical safety of gelatin nanoparticles (GNPs) using an in vitro method and also assessed the clinical safety and efficacy of the association of GNPs with three commonly used chemical UV filters (ethylhexyl dimethyl PABA, ethylhexyl methoxycinnamate and methoxydibenzoylmethane). The non-irritant and adequate safety profile under sun-exposed skin conditions of the nanomaterials and the emulsions qualified the products for clinical efficacy assays. The in vivo results indicated that the GNPs increased the antioxidant protection of the emulsions developed. However, the presence of rutin in the nanosized material did not enhance performance on the SPF test. In conclusion, these findings characterized the nanomaterials as an innovative platform for multifunctional bioactive sunscreens. Copyright © 2015 Elsevier B.V. All rights reserved.

Safety Evaluation of a Novel Strain of Bacteroides fragilis.

PubMed

Wang, Ye; Deng, Huimin; Li, Zhengchao; Tan, Yafang; Han, Yanping; Wang, Xiaoyi; Du, Zongmin; Liu, Yangyang; Yang, Ruifu; Bai, Yang; Bi, Yujing; Zhi, Fachao

2017-01-01

Commensal non-toxigenic Bacteroides fragilis confers powerful health benefits to the host, and has recently been identified as a promising probiotic candidate. We previously isolated B. fragilis strain ZY-312 and identified it as a novel strain based on 16S rRNA sequencing and morphological analyses. We also determined that ZY-312 displayed desirable probiotic properties, including tolerance to simulated digestive fluid, adherence, and in vitro safety. In this study, we aim to investigate whether ZY-312 meets the safety criteria required for probiotic bacteria through comprehensive and systematic evaluation. Consequently, the fatty acid profile, metabolite production, and biochemical activity of strain ZY-312 were found to closely resemble descriptions of B. fragilis in Bergey's manual. Taxonomic identification of strain ZY-312 based on whole genome sequencing indicated that ZY-312 and ATCC 25285 showed 99.99% similarity. The 33 putative virulence-associated factors identified in ZY-312 mainly encoded structural proteins and proteins with physiological activity, while the lack of bft indicated that ZY-312 was non-toxigenic. In vivo safety was proven in both normal and immune-deficient mice. The 11 identified antibiotic resistance genes were located on the chromosome rather than on a plasmid, ruling out the risk of plasmid-mediated transfer of antibiotic resistance. In vitro , ZY-312 showed resistance to cefepime, kanamycin, and streptomycin. Finally, and notably, ZY-312 exhibited high genetic stability after 100 passages in vitro . This study supplements the foundation work on the safety evaluation of ZY-312, and contributes to the development of the first probiotic representative from the dominant Bacteroidetes phylum.

Safety Evaluation of a Novel Strain of Bacteroides fragilis

PubMed Central

Deng, Huimin; Li, Zhengchao; Tan, Yafang; Han, Yanping; Wang, Xiaoyi; Du, Zongmin; Liu, Yangyang; Yang, Ruifu; Bai, Yang; Bi, Yujing; Zhi, Fachao

2017-01-01

Commensal non-toxigenic Bacteroides fragilis confers powerful health benefits to the host, and has recently been identified as a promising probiotic candidate. We previously isolated B. fragilis strain ZY-312 and identified it as a novel strain based on 16S rRNA sequencing and morphological analyses. We also determined that ZY-312 displayed desirable probiotic properties, including tolerance to simulated digestive fluid, adherence, and in vitro safety. In this study, we aim to investigate whether ZY-312 meets the safety criteria required for probiotic bacteria through comprehensive and systematic evaluation. Consequently, the fatty acid profile, metabolite production, and biochemical activity of strain ZY-312 were found to closely resemble descriptions of B. fragilis in Bergey’s manual. Taxonomic identification of strain ZY-312 based on whole genome sequencing indicated that ZY-312 and ATCC 25285 showed 99.99% similarity. The 33 putative virulence-associated factors identified in ZY-312 mainly encoded structural proteins and proteins with physiological activity, while the lack of bft indicated that ZY-312 was non-toxigenic. In vivo safety was proven in both normal and immune-deficient mice. The 11 identified antibiotic resistance genes were located on the chromosome rather than on a plasmid, ruling out the risk of plasmid-mediated transfer of antibiotic resistance. In vitro, ZY-312 showed resistance to cefepime, kanamycin, and streptomycin. Finally, and notably, ZY-312 exhibited high genetic stability after 100 passages in vitro. This study supplements the foundation work on the safety evaluation of ZY-312, and contributes to the development of the first probiotic representative from the dominant Bacteroidetes phylum. PMID:28367145

Use of a safety climate questionnaire in UK health care: factor structure, reliability and usability.

PubMed

Hutchinson, A; Cooper, K L; Dean, J E; McIntosh, A; Patterson, M; Stride, C B; Laurence, B E; Smith, C M

2006-10-01

To explore the factor structure, reliability, and potential usefulness of a patient safety climate questionnaire in UK health care. Four acute hospital trusts and nine primary care trusts in England. The questionnaire used was the 27 item Teamwork and Safety Climate Survey. Thirty three healthcare staff commented on the wording and relevance. The questionnaire was then sent to 3650 staff within the 13 NHS trusts, seeking to achieve at least 600 responses as the basis for the factor analysis. 1307 questionnaires were returned (36% response). Factor analyses and reliability analyses were carried out on 897 responses from staff involved in direct patient care, to explore how consistently the questions measured the underlying constructs of safety climate and teamwork. Some questionnaire items related to multiple factors or did not relate strongly to any factor. Five items were discarded. Two teamwork factors were derived from the remaining 11 teamwork items and three safety climate factors were derived from the remaining 11 safety items. Internal consistency reliabilities were satisfactory to good (Cronbach's alpha > or =0.69 for all five factors). This is one of the few studies to undertake a detailed evaluation of a patient safety climate questionnaire in UK health care and possibly the first to do so in primary as well as secondary care. The results indicate that a 22 item version of this safety climate questionnaire is useable as a research instrument in both settings, but also demonstrates a more general need for thorough validation of safety climate questionnaires before widespread usage.

Equilibrium drives of the low and high field side n = 2 plasma response and impact on global confinement

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

Paz-Soldan, C.; Logan, N. C.; Haskey, S. R.

The nature of the multi-modal n=2 plasma response and its impact on global confinement is studied as a function of the axisymmetric equilibrium pressure, edge safety factor, collisionality, and L-versus H-mode conditions. Varying the relative phase (ΔΦ UL) between upper and lower in-vessel coils demonstrates that different n=2 poloidal spectra preferentially excite different plasma responses. These different plasma response modes are preferentially detected on the tokamak high-field side (HFS) or low-field side (LFS) midplanes, have different radial extents, couple differently to the resonant surfaces, and have variable impacts on edge stability and global confinement. In all equilibrium conditions studied, themore » observed confinement degradation shares the same ΔΦ UL dependence as the coupling to the resonant surfaces given by both ideal (IPEC) and resistive (MARS-F) MHD computation. Varying the edge safety factor shifts the equilibrium field-line pitch and thus the ΔΦ UL dependence of both the global confinement and the n=2 magnetic response. As edge safety factor is varied, modeling finds that the HFS response (but not the LFS response), the resonant surface coupling, and the edge displacements near the X-point all share the same ΔΦ UL dependence. The LFS response magnitude is strongly sensitive to the core pressure and is insensitive to the collisionality and edge safety factor. This indicates that the LFS measurements are primarily sensitive to a pressure-driven kink-ballooning mode that couples to the core plasma. MHD modeling accurately reproduces these (and indeed all) LFS experimental trends and supports this interpretation. In contrast to the LFS, the HFS magnetic response and correlated global confinement impact is unchanged with plasma pressure, but is strongly reduced in high collisionality conditions in both H- and L-mode. This experimentally suggests the bootstrap current drives the HFS response through the kink-peeling mode drive, though surprisingly weak or no dependence on the bootstrap current is seen in modeling. Instead, modeling is revealed to be very sensitive to the details of the edge current profile and equilibrium truncation. Furthermore, holding truncation fixed, most HFS experimental trends are not captured, thus demonstrating a stark contrast between the robustness of the HFS experimental results and the sensitivity of its computation.« less

Equilibrium drives of the low and high field side n  =  2 plasma response and impact on global confinement

NASA Astrophysics Data System (ADS)

Paz-Soldan, C.; Logan, N. C.; Haskey, S. R.; Nazikian, R.; Strait, E. J.; Chen, X.; Ferraro, N. M.; King, J. D.; Lyons, B. C.; Park, J.-K.

2016-05-01

The nature of the multi-modal n  =  2 plasma response and its impact on global confinement is studied as a function of the axisymmetric equilibrium pressure, edge safety factor, collisionality, and L-versus H-mode conditions. Varying the relative phase (Δ {φ\\text{UL}} ) between upper and lower in-vessel coils demonstrates that different n  =  2 poloidal spectra preferentially excite different plasma responses. These different plasma response modes are preferentially detected on the tokamak high-field side (HFS) or low-field side (LFS) midplanes, have different radial extents, couple differently to the resonant surfaces, and have variable impacts on edge stability and global confinement. In all equilibrium conditions studied, the observed confinement degradation shares the same Δ {φ\\text{UL}} dependence as the coupling to the resonant surfaces given by both ideal (IPEC) and resistive (MARS-F) MHD computation. Varying the edge safety factor shifts the equilibrium field-line pitch and thus the Δ {φ\\text{UL}} dependence of both the global confinement and the n  =  2 magnetic response. As edge safety factor is varied, modeling finds that the HFS response (but not the LFS response), the resonant surface coupling, and the edge displacements near the X-point all share the same Δ {φ\\text{UL}} dependence. The LFS response magnitude is strongly sensitive to the core pressure and is insensitive to the collisionality and edge safety factor. This indicates that the LFS measurements are primarily sensitive to a pressure-driven kink-ballooning mode that couples to the core plasma. MHD modeling accurately reproduces these (and indeed all) LFS experimental trends and supports this interpretation. In contrast to the LFS, the HFS magnetic response and correlated global confinement impact is unchanged with plasma pressure, but is strongly reduced in high collisionality conditions in both H- and L-mode. This experimentally suggests the bootstrap current drives the HFS response through the kink-peeling mode drive, though surprisingly weak or no dependence on the bootstrap current is seen in modeling. Instead, modeling is revealed to be very sensitive to the details of the edge current profile and equilibrium truncation. Holding truncation fixed, most HFS experimental trends are not captured, thus demonstrating a stark contrast between the robustness of the HFS experimental results and the sensitivity of its computation.

Equilibrium drives of the low and high field side n = 2 plasma response and impact on global confinement

DOE PAGES

Paz-Soldan, C.; Logan, N. C.; Haskey, S. R.; ...

2016-03-31

The nature of the multi-modal n=2 plasma response and its impact on global confinement is studied as a function of the axisymmetric equilibrium pressure, edge safety factor, collisionality, and L-versus H-mode conditions. Varying the relative phase (ΔΦ UL) between upper and lower in-vessel coils demonstrates that different n=2 poloidal spectra preferentially excite different plasma responses. These different plasma response modes are preferentially detected on the tokamak high-field side (HFS) or low-field side (LFS) midplanes, have different radial extents, couple differently to the resonant surfaces, and have variable impacts on edge stability and global confinement. In all equilibrium conditions studied, themore » observed confinement degradation shares the same ΔΦ UL dependence as the coupling to the resonant surfaces given by both ideal (IPEC) and resistive (MARS-F) MHD computation. Varying the edge safety factor shifts the equilibrium field-line pitch and thus the ΔΦ UL dependence of both the global confinement and the n=2 magnetic response. As edge safety factor is varied, modeling finds that the HFS response (but not the LFS response), the resonant surface coupling, and the edge displacements near the X-point all share the same ΔΦ UL dependence. The LFS response magnitude is strongly sensitive to the core pressure and is insensitive to the collisionality and edge safety factor. This indicates that the LFS measurements are primarily sensitive to a pressure-driven kink-ballooning mode that couples to the core plasma. MHD modeling accurately reproduces these (and indeed all) LFS experimental trends and supports this interpretation. In contrast to the LFS, the HFS magnetic response and correlated global confinement impact is unchanged with plasma pressure, but is strongly reduced in high collisionality conditions in both H- and L-mode. This experimentally suggests the bootstrap current drives the HFS response through the kink-peeling mode drive, though surprisingly weak or no dependence on the bootstrap current is seen in modeling. Instead, modeling is revealed to be very sensitive to the details of the edge current profile and equilibrium truncation. Furthermore, holding truncation fixed, most HFS experimental trends are not captured, thus demonstrating a stark contrast between the robustness of the HFS experimental results and the sensitivity of its computation.« less

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

2009 Human Factors and Roadway Safety Workshop : Overviews of Safety Initiatives in Iowa [SD .WMV (720x480/29fps/80.2 MB)

DOT National Transportation Integrated Search

2009-11-05

Iowa Department of Transportation Research and Technology Bureau video presentation from the 2009 human factors and roadway safety workshop session titled: Overview of Safety Initiatives in Iowa : Tom Welch, Iowa DOT Highway Division Safety Engineer,...

Applications of aerospace technology in industry, a technology transfer profile: Fire safety

NASA Technical Reports Server (NTRS)

Kottenstette, J. P.; Freeman, J. E.; Heins, C. R.; Hildred, W. M.; Johnson, F. D.; Staskin, E. R.

1971-01-01

The fire safety field is considered as being composed of three parts: an industry, a technology base, and a user base. An overview of the field is presented, including a perspective on the magnitude of the national fire safety problem. Selected NASA contributions to the technology of fire safety are considered. Communication mechanisms, particularly conferences and publications, used by NASA to alert the community to new developments in the fire safety field, are reviewed. Several examples of nonaerospace applications of NASA-generated fire safety technology are also presented. Issues associated with attempts to transfer this technology from the space program to other sectors of the American economy are outlined.

Assessment of the impact of dipped guideways on urban rail transit systems: Ventilation and safety requirements

NASA Technical Reports Server (NTRS)

1982-01-01

The ventilation and fire safety requirements for subway tunnels with dipped profiles between stations as compared to subway tunnels with level profiles were evaluated. This evaluation is based upon computer simulations of a train fire emergency condition. Each of the tunnel configurations evaluated was developed from characteristics that are representative of modern transit systems. The results of the study indicate that: (1) The level tunnel system required about 10% more station cooling than dipped tunnel systems in order to meet design requirements; and (2) The emergency ventilation requirements are greater with dipped tunnel systems than with level tunnel systems.

Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment

PubMed Central

2013-01-01

Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients. PMID:23697612

Is the use of colloids for fluid replacement harmless in children?

PubMed

Saudan, Sonja

2010-06-01

Albumin has been regarded as the gold standard for maintaining adequate colloid osmotic pressure in children, but increased cost, the lack of clear-cut benefits for survival, and fear of transmission of unknown viruses have contributed to its replacement by hydroxyethyl starch and gelatin preparations. Each of the synthetic colloids has unique physicochemical characteristics that determine their likely efficacy and adverse effect profile. This review will examine the advantages and disadvantages of the use of different colloid solutions in children with a particular focus on their safety profile. Dextrans are rarely used because of their negative effects on coagulation and potential for anaphylactic reactions. Gelatin and albumin have little effect on hemostasis, but the disadvantages of gelatin include its high anaphylactoid potential and limited beneficial volume effect. Tetrastarches have significantly fewer adverse effects on coagulation and renal function than the older hydroxyethyl starches and are now approved for children. Dissolving tetrastarches in a plasma-adapted, balanced solution rather than in saline further improves safety with regard to coagulation and acid-base balance. Tetrastarches offer the best currently available compromise between cost-effectiveness and safety profile in children with preexisting normal renal function and coagulation.

Factors Influencing Implementation of OHSAS 18001 in Indian Construction Organizations: Interpretive Structural Modeling Approach

PubMed Central

Rajaprasad, Sunku Venkata Siva; Chalapathi, Pasupulati Venkata

2015-01-01

Background Construction activity has made considerable breakthroughs in the past two decades on the back of increases in development activities, government policies, and public demand. At the same time, occupational health and safety issues have become a major concern to construction organizations. The unsatisfactory safety performance of the construction industry has always been highlighted since the safety management system is neglected area and not implemented systematically in Indian construction organizations. Due to a lack of enforcement of the applicable legislation, most of the construction organizations are forced to opt for the implementation of Occupational Health Safety Assessment Series (OHSAS) 18001 to improve safety performance. Methods In order to better understand factors influencing the implementation of OHSAS 18001, an interpretive structural modeling approach has been applied and the factors have been classified using matrice d'impacts croises-multiplication appliqué a un classement (MICMAC) analysis. The study proposes the underlying theoretical framework to identify factors and to help management of Indian construction organizations to understand the interaction among factors influencing in implementation of OHSAS 18001. Results Safety culture, continual improvement, morale of employees, and safety training have been identified as dependent variables. Safety performance, sustainable construction, and conducive working environment have been identified as linkage variables. Management commitment and safety policy have been identified as the driver variables. Conclusion Management commitment has the maximum driving power and the most influential factor is safety policy, which states clearly the commitment of top management towards occupational safety and health. PMID:26929828

Predictors of Hospital Nurses' Safety Practices: Work Environment, Workload, Job Satisfaction, and Error Reporting.

PubMed

Chiang, Hui-Ying; Hsiao, Ya-Chu; Lee, Huan-Fang

Nurses' safety practices of medication administration, prevention of falls and unplanned extubations, and handover are essentials to patient safety. This study explored the prediction between such safety practices and work environment factors, workload, job satisfaction, and error-reporting culture of 1429 Taiwanese nurses. Nurses' job satisfaction, error-reporting culture, and one environmental factor of nursing quality were found to be major predictors of safety practices. The other environment factors related to professional development and participation in hospital affairs and nurses' workload had limited predictive effects on the safety practices. Increasing nurses' attention to patient safety by improving these predictors is recommended.

Validation of the group nuclear safety climate questionnaire.

PubMed

Navarro, M Felisa Latorre; Gracia Lerín, Francisco J; Tomás, Inés; Peiró Silla, José María

2013-09-01

Group safety climate is a leading indicator of safety performance in high reliability organizations. Zohar and Luria (2005) developed a Group Safety Climate scale (ZGSC) and found it to have a single factor. The ZGSC scale was used as a basis in this study with the researchers rewording almost half of the items on this scale, changing the referents from the leader to the group, and trying to validate a two-factor scale. The sample was composed of 566 employees in 50 groups from a Spanish nuclear power plant. Item analysis, reliability, correlations, aggregation indexes and CFA were performed. Results revealed that the construct was shared by each unit, and our reworded Group Safety Climate (GSC) scale showed a one-factor structure and correlated to organizational safety climate, formalized procedures, safety behavior, and time pressure. This validation of the one-factor structure of the Zohar and Luria (2005) scale could strengthen and spread this scale and measure group safety climate more effectively. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Calibration of highway safety manual work zone crash modification factors.

DOT National Transportation Integrated Search

2014-06-01

The Highway Safety Manual is the national safety manual that provides quantitative methods for analyzing highway safety. The : HSM presents crash modification factors related to work zone characteristics such as work zone duration and length. These c...

Relationship between organizational justice and organizational safety climate: do fairness perceptions influence employee safety behaviour?

PubMed

Gyekye, Seth Ayim; Haybatollahi, Mohammad

2014-01-01

This study investigated the relationships between organizational justice, organizational safety climate, job satisfaction, safety compliance and accident frequency. Ghanaian industrial workers participated in the study (N = 320). Safety climate and justice perceptions were assessed with Hayes, Parender, Smecko, et al.'s (1998) and Blader and Tyler's (2003) scales respectively. A median split was performed to dichotomize participants into 2 categories: workers with positive and workers with negative justice perceptions. Confirmatory factors analysis confirmed the 5-factor structure of the safety scale. Regression analyses and t tests indicated that workers with positive fairness perceptions had constructive perspectives regarding workplace safety, expressed greater job satisfaction, were more compliant with safety policies and registered lower accident rates. These findings provide evidence that the perceived level of fairness in an organization is closely associated with workplace safety perception and other organizational factors which are important for safety. The implications for safety research are discussed.

Aviation occupant survival factors: an empirical study of the SQ006 accident.

PubMed

Chang, Yu-Hern; Yang, Hui-Hua

2010-03-01

We present an empirical study of Singapore Airline (SIA) flight SQ006 to illustrate the critical factors that influence airplane occupant survivability. The Fuzzy Delphi Method was used to identify and rank the survival factors that may reduce injury and fatality in potentially survivable accidents. This is the first attempt by a group from both the public and private sectors in Taiwan to focus on cabin-safety issues related to survival factors. We designed a comprehensive survey based on our discussions with aviation safety experts. We next designed an array of important cabin-safety dimensions and then investigated and selected the critical survival factors for each dimension. Our findings reveal important cabin safety and survivability information that should provide a valuable reference for developing and evaluating aviation safety programs. We also believe that the results will be practical for designing cabin-safety education material for air travelers. Finally, the major contribution of this research is that it has identified 47 critical factors that influence accident survivability; therefore, it may encourage improvements that will promote more successful cabin-safety management. Copyright 2009 Elsevier Ltd. All rights reserved.

Clinical safety and effectiveness of transversus abdominis plane (TAP) block in post-operative analgesia: a systematic review and meta-analysis.

PubMed

Ma, Ning; Duncan, Joanna K; Scarfe, Anje J; Schuhmann, Susanne; Cameron, Alun L

2017-06-01

Transversus abdominis plane (TAP) blocks can provide analgesia postoperatively for a range of surgeries. Abundant clinical trials have assessed TAP block showing positive analgesic effects. This systematic review assesses safety and effectiveness outcomes of TAP block in all clinical settings, comparing with both active (standard care) and inactive (placebo) comparators. PubMed, EMBASE, The Cochrane Library and the University of York CRD databases were searched. RCTs were screened for their eligibility and assessed for risk of bias. Meta-analyses were performed on available data. TAP block showed an equivalent safety profile to all comparators in the incidence of nausea (OR = 1.07) and vomiting (OR = 0.81). TAP block was more effective in reducing morphine consumption [MD = 13.05, 95% CI (8.33, 51.23)] and in delaying time to first analgesic request [MD = 123.49, 95% CI (48.59, 198.39)]. Postoperative pain within 24 h was reduced or at least equivalent in TAP block compared to its comparators. Therefore, TAP block is a safe and effective procedure compared to standard care, placebo and other analgesic techniques. Further research is warranted to investigate whether the TAP block technique can be improved by optimizing dose and technique-related factors.

The use of sibutramine in the management of obesity and related disorders: an update.

PubMed

Tziomalos, Konstantinos; Krassas, Gerasimos E; Tzotzas, Themistoklis

2009-01-01

To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity-related disorders. The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesity-associated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality. Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality.

The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations.

PubMed

Pardo, Gabriel; Jones, David E

2017-12-01

The treatment landscape for relapsing forms of multiple sclerosis (RMS) has expanded considerably over the last 10 years with the approval of multiple new disease-modifying therapies (DMTs), and others in late-stage clinical development. All DMTs for RMS are believed to reduce central nervous system immune-mediated inflammatory processes, which translate into demonstrable improvement in clinical and radiologic outcomes. However, some DMTs are associated with long-lasting effects on the immune system and/or serious adverse events, both of which may complicate the use of subsequent therapies. When customizing a treatment program, a benefit-risk assessment must consider multiple factors, including the efficacy of the DMT to reduce disease activity, the short- and long-term safety and immunologic profiles of each DMT, the criteria used to define switching treatment, and the risk tolerance of each patient. A comprehensive benefit-risk assessment can only be achieved by evaluating the immunologic, safety, and efficacy data for DMTs in the controlled clinical trial environment and the postmarketing clinical practice setting. This review is intended to help neurologists make informed decisions when treating RMS by summarizing the known data for each DMT and raising awareness of the multiple considerations involved in treating people with RMS throughout the entire course of their disease.

The use of sibutramine in the management of obesity and related disorders: An update

PubMed Central

Tziomalos, Konstantinos; Krassas, Gerasimos E; Tzotzas, Themistoklis

2009-01-01

Aims: To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity-related disorders. Methods and results: The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesity-associated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality. Conclusions: Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality. PMID:19475780

[Preclinical safety evaluation of chloral hydrate after topical application using the example of psoriatic itch].

PubMed

Wohlrab, J; Gilbrich, F; Wolff, L; Fischer, M; Philipp, S

2017-03-01

Psoriasis is known today as a T‑cell-mediated autoimmunological systemic disease. The chronic inflammatory processes involve neuroimmunological factors that are held responsible not only for various aspects of psychiatric-neurological comorbidities but also for neurosensory problems, primarily itching. Amongst other things, the significance of GABA A receptors are often discussed in this context. The topical use of chloral hydrate in semisolid preparations for antipruritic therapy goes back to Neisser and is currently experiencing a revival in individually manufactured formulations. However, it is currently unknown whether the unwanted side effects that are described for systemic use of chloral hydrate are also relevant for topical application. For lack of clinical safety data, preclinical tests for cutaneous cytotoxicity and calculations for systemic bioavailability after topical application have been performed. The present data cannot fully remove safety concerns for topical application of chloral hydrate in the formulation favoured by the NRF (Neues Rezepturformularium)-the so-called 1‑2-3-cream. A twice daily use of the 1‑2-3-cream on a maximum of 10% of the body surface can be regarded as safe. For a better assessment of harmlessness, tests for cutaneous bioavailability (concentration-time profile) on human skin and clinical studies would be necessary.

Investigating ethnic minorities' perceptions of safety climate in the construction industry.

PubMed

Chan, Albert P C; Wong, Francis K W; Hon, Carol K H; Lyu, Sainan; Javed, Arshad Ali

2017-12-01

An increasing number of ethnic minorities (EMs) have been employed in the construction industry to alleviate severe labor shortages in many countries. Unfortunately, statistics show that EMs have higher fatal and non-fatal occupational injury rates than their local counterparts. However, EMs are often underrepresented in safety climate (SC) research as they are difficult to reach and gauge their perception. A positive relationship has been widely found between SC and safety performance. Understanding the safety perceptions of EMs helps to reduce injuries and improve their safety performance. Based on a sample of 320 EMs from 20 companies in the construction industry, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to identify the SC factors of EMs, and validate the extracted factors, respectively. Multivariate analysis of variance was undertaken to examine mean differences in perceptions of SC by personal characteristics. Three SC factors for EMs encapsulating 16 variables were identified through EFA. The hypothesized CFA model for a three-factor structure derived from EFA showed a satisfactory goodness-of-fit, composite reliability, and construct validity. Three SC factors were identified, namely: (a) safety management commitment, safety resources, and safety communication; (b) employee's involvement and workmate's influence; and (c) perception of safety rules, procedures and risks. The perceptions of SC differed significantly by nationality, marital status, the number of family members supported, and drinking habit. This study reveals the perception of EMs toward SC. The findings highlight the areas for safety improvement and provide leading indicators for safety performance of EMs. The findings are also enlightening for countries with a number of EMs, such as the United Sates, the United Kingdom, Australia, Singapore, and the Middle East. Copyright © 2017. Published by Elsevier Ltd.

16 CFR 1105.2 - Factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Factors. 1105.2 Section 1105.2 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CONTRIBUTIONS TO COSTS OF PARTICIPANTS IN DEVELOPMENT OF CONSUMER PRODUCT SAFETY STANDARDS § 1105.2 Factors. The Commission...

Evaluating the impact of grade crossing safety factors through signal detection theory

DOT National Transportation Integrated Search

2012-10-22

The purpose of this effort was to apply signal detection theory to descriptively model the impact : of five grade crossing safety factors to understand their effect on driver decision making. The : safety factors consisted of: improving commercial mo...

10 CFR 32.74 - Manufacture and distribution of sources or devices containing byproduct material for medical use.

Code of Federal Regulations, 2013 CFR

2013-01-01

... accidents; (iv) For devices containing byproduct material, the radiation profile of a prototype device; (v... source or device pertinent to an evaluation of its radiation safety, including: (i) The byproduct...) Instructions for handling and storing the source or device from the radiation safety standpoint; these...

10 CFR 32.74 - Manufacture and distribution of sources or devices containing byproduct material for medical use.

Code of Federal Regulations, 2014 CFR

2014-01-01

... accidents; (iv) For devices containing byproduct material, the radiation profile of a prototype device; (v... source or device pertinent to an evaluation of its radiation safety, including: (i) The byproduct...) Instructions for handling and storing the source or device from the radiation safety standpoint; these...

Immunogenicity, effectiveness and safety of combined hepatitis A and B vaccine: a systematic literature review.

PubMed

Bakker, Marina; Bunge, Eveline M; Marano, Cinzia; de Ridder, Marc; De Moerlooze, Laurence

2016-07-01

Hepatitis A and B are two of the most common vaccine-preventable diseases and vaccination for Hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for those at risk of contracting HAV and/or HBV through their occupation, travel or lifestyle. To describe the vaccine efficacy, immunogenicity, effectiveness and safety of the combined vaccine against hepatitis A and hepatitis B. A systematic review of the literature published between 1990 and 2015. Anti-HAV seropositivity rates ranged from 96.2% to 100% and anti-HBs seroprotection rates from 82% to 100%. Antibodies persisted up to 15 years and geometric mean concentration (GMC) remained above the seropositivity cut-off value for both. Anti-HAV and anti-HBs immune responses were lower in less immunocompetent individuals one month after completion of the immunization schedule. The safety profiles of Twinrix(TM) and monovalent hepatitis A and B vaccines were similar. The vaccine offers satisfactory long-term immunogenicity rates, expected duration of protection and safety profile similar to the monovalent hepatitis A or B vaccines.

Patient safety in surgical environments: cross-countries comparison of psychometric properties and results of the Norwegian version of the Hospital Survey on Patient Safety.

PubMed

Haugen, Arvid S; Søfteland, Eirik; Eide, Geir E; Nortvedt, Monica W; Aase, Karina; Harthug, Stig

2010-09-22

How hospital health care personnel perceive safety climate has been assessed in several countries by using the Hospital Survey on Patient Safety (HSOPS). Few studies have examined safety climate factors in surgical departments per se. This study examined the psychometric properties of a Norwegian translation of the HSOPS and also compared safety climate factors from a surgical setting to hospitals in the United States, the Netherlands and Norway. This survey included 575 surgical personnel in Haukeland University Hospital in Bergen, an 1100-bed tertiary hospital in western Norway: surgeons, operating theatre nurses, anaesthesiologists, nurse anaesthetists and ancillary personnel. Of these, 358 returned the HSOPS, resulting in a 62% response rate. We used factor analysis to examine the applicability of the HSOPS factor structure in operating theatre settings. We also performed psychometric analysis for internal consistency and construct validity. In addition, we compared the percent of average positive responds of the patient safety climate factors with results of the US HSOPS 2010 comparative data base report. The professions differed in their perception of patient safety climate, with anaesthesia personnel having the highest mean scores. Factor analysis using the original 12-factor model of the HSOPS resulted in low reliability scores (r = 0.6) for two factors: "adequate staffing" and "organizational learning and continuous improvement". For the remaining factors, reliability was ≥ 0.7. Reliability scores improved to r = 0.8 by combining the factors "organizational learning and continuous improvement" and "feedback and communication about error" into one six-item factor, supporting an 11-factor model. The inter-item correlations were found satisfactory. The psychometric properties of the questionnaire need further investigations to be regarded as reliable in surgical environments. The operating theatre personnel perceived their hospital's patient safety climate far more negatively than the health care personnel in hospitals in the United States and with perceptions more comparable to those of health care personnel in hospitals in the Netherlands. In fact, the surgical personnel in our hospital may perceive that patient safety climate is less focused in our hospital, at least compared with the results from hospitals in the United States.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

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

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com; Weng, Zuquan; Sun, Liya

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. Inmore » the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.« less

Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

PubMed

Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

2016-06-22

Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.

Factors influencing patient safety in Sweden: perceptions of patient safety officers in the county councils

PubMed Central

2013-01-01

Background National, regional and local activities to improve patient safety in Sweden have increased over the last decade. There are high ambitions for improved patient safety in Sweden. This study surveyed health care professionals who held key positions in their county council’s patient safety work to investigate their perceptions of the conditions for this work, factors they believe have been most important in reaching the current level of patient safety and factors they believe would be most important for achieving improved patient safety in the future. Methods The study population consisted of 218 health care professionals holding strategic positions in patient safety work in Swedish county councils. Using a questionnaire, the following topics were analysed in this study: profession/occupation; number of years involved in a designated task on patient safety issues; knowledge/overview of the county council’s patient safety work; ability to influence this work; conditions for this work; and the importance of various factors for current and future levels of patient safety. Results The response rate to the questionnaire was 79%. The conditions that had the highest number of responses in complete agreement were “patients’ involvement is important for patient safety” and “patient safety work has good support from the county council’s management”. Factors that were considered most important for achieving the current level of patient safety were root cause and risk analyses, incident reporting and the Swedish Patient Safety Law. An organizational culture that encourages reporting and avoids blame was considered most important for improved patient safety in the future, closely followed by improved communication between health care practitioners and patients. Conclusion Health care professionals with important positions in the Swedish county councils’ patient safety work believe that conditions for this work are somewhat constrained. They attribute the current levels of patient safety to a broad range of factors and believe that many different solutions can contribute to enhanced patient safety in the future, suggesting that this work must be multifactorial. PMID:23391301

Evaluation on the Efficiency of Subsurface Drainage in Chiu-Fen Landslide at Northern Taiwan

NASA Astrophysics Data System (ADS)

Ying, L. Y.; Lin, D. G.

2015-12-01

For administrative district, the Chiu-Fen landslide is situated at northern Taiwan and comes within the jurisdiction of Ruei-Fang district, New Taipei City Government. Chiu-Fen village is a famous spot for sightseeing and tourism in Southeast Asia. In the last decade, for economic purpose, a vast area of slope land in Chiu-Fen area was reclaimed into business and commercial districts. However, due to the complicated geological and hydrological conditions, improper reclamation, and lack of appropriate soil and water conservation facilities, large scale landslides are frequently triggered by typhoon rainfall and causes damages to the transportation and residential building in the community. As a consequence, the government initiated a comprehensive field investigations and remediation plans to stabilize the landslide from 1997 and the remediation works were concentrated on subsurface drainages, namely the application of drainage well (a vertical shaft with multi-level horizontal drainage boreholes). To investigate the efficiency of drainage wells on the landslide, the A1-profile in the landslide which covers the drainage wells W2 and W4 was selected for a series of rainfall seepage and slope stability analyses. In addition, a 48-hrs design rainfall with return period of 25, 50 and 100 years based on the local meteorological data bank was adopted for the analyses. The numerical results indicate the factor safety FS of the three potential sliding surfaces within A1-profile are constantly keeping greater than one (FS > 1.0) and without decreasing with the elapsed time during rainfall. This implies that the subsurface drainage works can drain off the infiltrated rainwater from a high intensity and long duration rainfall and preserve the slope stability of landslides from deterioration. Finally, the efficiency of the drainage wells can be evaluated quantitatively in terms of the time-dependent factor of safety and the pore water pressure distribution on several potential sliding surfaces.

Preliminary numerical simulation for shallow strata stability of coral reef in South China Sea

NASA Astrophysics Data System (ADS)

Tang, Qinqin; Zhan, Wenhuan; Zhang, Jinchang

2017-04-01

Coral reefs are the geologic material and special rock and soil, which live in shallow water of the tropic ocean and are formed through biological and geological action. Since infrastructure construction is being increasingly developed on coral reefs during recent years, it is necessary to evaluate the shallow strata stability of coral reefs in the South China Sea. The paper is to study the borehole profiles for shallow strata of coral reefs in the South China Sea, especially in the hydrodynamic marine environment?, and to establish a geological model for numerical simulation with Geo-Studio software. Five drilling holes show a six-layer shallow structure of South China Sea, including filling layer, mid-coarse sand, coral sand gravel, fine sand, limestone debris and reef limestone. The shallow coral reef profile next to lagoon is similar to "layers cake", in which the right side close to the sea is analogous to "block cake". The simulation results show that coral reef stability depends on wave loads and earthquake strength, as well as the physical properties of coral reefs themselves. The safety factor of the outer reef is greater than 10.0 in the static condition, indicating that outer reefs are less affected by the wave and earthquake. However, the safety factor next to lagoon is ranging from 0.1 to 4.9. The main reason for the variations that the strata of coral reefs close to the sea are thick. For example, the thickness of reef limestone is more than 10 m and equivalent to the block. When the thickness of inside strata is less than 10 m, they show weak engineering geological characteristics. These findings can provide useful information for coral reef constructions in future. This work was funded by National Basic Research Program of China (contract: 2013CB956104) and National Natural Science Foundation of China (contract: 41376063).

2009 Human Factors and Roadway Safety Workshop : Opening Session [SD .WMV (720x480/29fps/546.0 MB)

DOT National Transportation Integrated Search

2009-11-05

Iowa Department of Transportation Research and Technology Bureau video presentation from the 2009 human factors and roadway safety workshop session titled: 2009 Human Factors and Roadway Safety Workshop Opening Session : Sandra Larson, director, Iowa...

14 CFR 27.303 - Factor of safety.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Factor of safety. 27.303 Section 27.303 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Strength Requirements General § 27.303 Factor of safety. Unless...

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2).

PubMed

Simonneau, Gérald; D'Armini, Andrea M; Ghofrani, Hossein-Ardeschir; Grimminger, Friedrich; Hoeper, Marius M; Jansa, Pavel; Kim, Nick H; Wang, Chen; Wilkins, Martin R; Fritsch, Arno; Davie, Neil; Colorado, Pablo; Mayer, Eckhard

2015-05-01

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit-risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat. Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC). Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd 6MWD had changed by +51±62 m (n=172) versus CHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176) versus CHEST-1 baseline (n=236). Long-term riociguat had a favourable benefit-risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year. Copyright ©ERS 2015.

Clinical strategies to aim an adequate safety profile for patients and effective training for surgical residents: The laparoscopic cholecystectomy model.

PubMed

Bresadola, Vittorio; Pravisani, Riccardo; Pighin, Marina; Seriau, Luca; Cherchi, Vittorio; Giuseppe, Sergio; Risaliti, Andrea

2016-11-01

Training programs for resident surgeons represent a challenge for the mentoring activity. The aim of the present study is to investigate the impact of our training program for laparoscopic cholecystectomy on patient's safety and on the modulation of the residents' exposure to clinical scenario with different grades of complexity. This is a retrospective study based on a clinical series of laparoscopic cholecystectomy performed in a teaching hospital. Study population was grouped according to the expertise of the attending primary operator among resident surgeons. Four groups were identified: consultant (C), senior resident (SR); intermediate level resident (IR); junior resident (JR). The intraoperative and postoperative outcomes were confronted to evaluate the patient's safety profile. 447 patients were submitted to LC: 96 cases were operated by a C, 200 by SR, 112 by IR and 39 by JR. The mean operative time was the longest for the JR group. A statistically higher rate of conversion to open approach was registered in C and IR groups in comparison to JR and SR groups. However, in C and IR groups, patients had worse ASA score, higher BMI and more frequent past history of previous abdominal surgery, cholecystitis or pancreatitis. Overall, it was not registered any statistically significant difference among the groups in terms of length of hospital stay and prevalence of major postoperative complications. Applying an educational model based on both graduated levels of responsibility and modulated grade of clinical complexity can guarantee an high safety profile.

Safety and Antioxidant Efficacy Profiles of Rutin-Loaded Ethosomes for Topical Application.

PubMed

Cândido, Thalita Marcílio; De Oliveira, Camila Areias; Ariede, Maíra Bueno; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

2018-05-01

Topical application of dermocosmetics containing antioxidant and/or the intake of antioxidants through diet or supplementation are remarkable tools in an attempt to slow down some of the harmful effects of free radicals. Rutin is a strong antioxidant compound used in food and pharmaceutical industries. It was established that rutin presents a low skin permeation rate, a property that could be considered an inconvenience to the satisfactory action for a dermocosmetic formulation to perform its antioxidant activity onto the skin. Therefore, it is indispensable to improve its delivery, aiming at increasing its antioxidant capacity in deeper layers of the epidermis, being a possibility to associate the rutin to liposomal vesicles, such as ethosomes. Thus, in this work, the pre-clinical safety of rutin-loaded ethosomes was investigated employing an in vitro method, and the clinical safety and efficacy were also assessed. Rutin-loaded ethosomes were efficaciously obtained in a nanoscale dimension with a relevant bioactive compound loading (80.2%) and provided antioxidant in vitro activity in comparison with the blank sample. Pre-clinical and clinical safety assays assured the innocuous profile of the rutin-loaded ethosomes. The ethosomes containing the bioactive compound accomplished a more functional delivery system profile, since in the tape stripping assay, the deeper layers presented higher rutin amounts than the active delivered in its free state. However, the ex vivo antioxidant efficacy test detected no positive antioxidant activity from the rutin-loaded ethosomes, even though the in vitro assay demonstrated an affirmative antioxidant action.

Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

PubMed Central

Schäfer, Birgit; Holzer, Georg W.; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A.; Kreil, Thomas R.; Barrett, P. Noel; Falkner, Falko G.

2011-01-01

Background Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. Methodology/Principal Findings A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 105 TCID50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. Conclusions/Significance The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice. PMID:21931732

Patient safety during assistant propelled wheelchair transfers: the effect of the seat cushion on risk of falling.

PubMed

Okunribido, Olanrewaju O

2013-01-01

This article is a report of a study of the effect of the seat cushion on risk of falling from a wheelchair. Two laboratory studies and simulated assistant propelled wheelchair transfers were conducted with four healthy female participants. For the laboratory studies there were three independent variables: trunk posture (upright/flexed forward), seat cushion (flat polyurethane/propad low profile), and feet condition (dangling/supported), and two dependent variables: occupied wheelchair (wheelchair) center of gravity (CG), and stability. For the simulated transfers there was one independent variable: seat cushion (flat polyurethane/propad low profile), and one dependent variable: perception of safety (risk of falling). Results showed that the wheelchair CG was closer to the front wheels, and stability lower for the propad low profile cushion compared to the polyurethane cushion, when the participants sat with their feet dangling. During the simulated transfers, sitting on the propad low profile cushion caused participants to feel more apprehensive (anxious or uneasy) compared to sitting on the polyurethane cushion. The findings can contribute to the assessment of risk and care planning of non-ambulatory wheelchair users.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

PubMed

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern. After 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

Effectiveness and safety of generic version of abacavir/lamivudine and efavirenz in treatment naïve HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2011-2012.

PubMed

Galindo, Jaime; Amariles, Pedro; Mueses-Marín, Héctor F; Hincapié, Jaime A; González-Avendaño, Sebastián; Galindo-Orrego, Ximena

2016-10-03

Generic drug policies are often associated with concerns about the quality and effectiveness of these products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs. The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and efavirenz in treatment-naïve HIV-infected patients. A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients 18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that provides comprehensive outpatient consultation and continuing care. The primary end-point was to achieve viral load <40 copies/mL at 12 months after baseline to assess effectiveness. Secondary end-point of the study were 1) to asses increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness, and 2) to assess both gastrointestinal, skin, and central nervous system symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as safety profile. Data were determined at baseline, 3, 6, and 12 months. Close clinical monitoring and pharmaceutical care were used for data collection. Wilcoxon matched-pairs signed-rank test was used to compare proportions or medians. Sixty patients were invited to participate in the study; 42 were enrolled and 33 completed the follow-up. Of the nine patients excluded from the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42 patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1 RNA <40 copies/mL. There was a significant increase (172 cells/mm 3 ) in the median for CD4 T lymphocyte count. The adverse events were mild and met the safety profile for this antiretroviral regimen, mainly of central nervous system symptoms, skin rash, lipid abnormalities, and an increase of 2 % in the median of the percentage of cardiovascular risk. The clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary ARV drugs. Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000202 . Registered 19 November 2015.

Clinical safety and efficacy of "filgrastim biosimilar 2" in Japanese patients in a post-marketing surveillance study.

PubMed

Tamura, Kazuo; Hashimoto, Kazue; Nishikawa, Kiyohiro

2018-05-01

We conducted a post-marketing surveillance to evaluate the safety and efficacy of TKN732, approved as "filgrastim biosimilar 2", in Japanese patients who developed neutropenia in the course of cancer chemotherapy or hematopoietic stem cell transplantation. A total of 653 patients were registered during the 2-year enrollment period starting from May 2013, and 627 and 614 patients were eligible for safety and efficacy analyses of the G-CSF biosimilar, respectively. Forty-three adverse drug reactions were reported in 33 patients (5.26%). Back pain was most frequently observed and reported in 20 patients (3.19%), followed by pyrexia (1.28%) and bone pain (0.96%). Risk factors for adverse reactions identified by logistic regression analyses were younger age, presence of past medical history, and lower total dose at the onset of adverse reactions. Among the 576 cancer patients who developed Grade 2-4 neutropenia after chemotherapy, recovery to Grade 1/0 was reported in 553 patients (96%) following filgrastim biosimilar 2 treatment. The median duration of neutrophil counts below 1500/μL was 5 days. In addition, all 11 patients who underwent hematopoietic stem cell transplantation had good responses to filgrastim biosimilar 2. In conclusion, this study showed that filgrastim biosimilar 2 has a similar safety profile and comparable effects to the original G-CSF product in the real world clinical setting. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Safety climate and attitude as evaluation measures of organizational safety.

PubMed

Isla Díaz, R; Díaz Cabrera, D

1997-09-01

The main aim of this research is to develop a set of evaluation measures for safety attitudes and safety climate. Specifically it is intended: (a) to test the instruments; (b) to identify the essential dimensions of the safety climate in the airport ground handling companies; (c) to assess the quality of the differences in the safety climate for each company and its relation to the accident rate; (d) to analyse the relationship between attitudes and safety climate; and (e) to evaluate the influences of situational and personal factors on both safety climate and attitude. The study sample consisted of 166 subjects from three airport companies. Specifically, this research was centered on ground handling departments. The factor analysis of the safety climate instrument resulted in six factors which explained 69.8% of the total variance. We found significant differences in safety attitudes and climate in relation to type of enterprise.

The safety of vedolizumab for ulcerative colitis and Crohn's disease

PubMed Central

Colombel, Jean-Frédéric; Sands, Bruce E; Rutgeerts, Paul; Sandborn, William; Danese, Silvio; D'Haens, Geert; Panaccione, Remo; Loftus, Edward V; Sankoh, Serap; Fox, Irving; Parikh, Asit; Milch, Catherine; Abhyankar, Brihad; Feagan, Brian G

2017-01-01

Objective Vedolizumab is a gut-selective antibody to α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab. Design Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p<0.0001), corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p<0.0001). Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study. Eighteen vedolizumab-exposed patients (<1%) were diagnosed with a malignancy. Conclusions Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. Trial registration number NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933. PMID:26893500

Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients.

PubMed

Gligorov, J; Ataseven, B; Verrill, M; De Laurentiis, M; Jung, K H; Azim, H A; Al-Sakaff, N; Lauer, S; Shing, M; Pivot, X

2017-09-01

To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC. Copyright © 2017 Elsevier Ltd. All rights reserved.

The clinical safety of high-dose piracetam--its use in the treatment of acute stroke.

PubMed

De Reuck, J; Van Vleymen, B

1999-03-01

Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.

Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells.

PubMed

Trevisan, Marta; Desole, Giovanna; Costanzi, Giulia; Lavezzo, Enrico; Palù, Giorgio; Barzon, Luisa

2017-01-20

Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from adult somatic cells. After the pioneering work by Yamanaka, who first generated iPSCs by retroviral transduction of four reprogramming factors, several alternative methods to obtain iPSCs have been developed in order to increase the yield and safety of the process. However, the question remains open on whether the different reprogramming methods can influence the pluripotency features of the derived lines. In this study, three different strategies, based on retroviral vectors, episomal vectors, and Sendai virus vectors, were applied to derive iPSCs from human fibroblasts. The reprogramming efficiency of the methods based on episomal and Sendai virus vectors was higher than that of the retroviral vector-based approach. All human iPSC clones derived with the different methods showed the typical features of pluripotent stem cells, including the expression of alkaline phosphatase and stemness maker genes, and could give rise to the three germ layer derivatives upon embryoid bodies assay. Microarray analysis confirmed the presence of typical stem cell gene expression profiles in all iPSC clones and did not identify any significant difference among reprogramming methods. In conclusion, the use of different reprogramming methods is equivalent and does not affect gene expression profile of the derived human iPSCs.

Alpharetroviral Vector-mediated Gene Therapy for X-CGD: Functional Correction and Lack of Aberrant Splicing

PubMed Central

Kaufmann, Kerstin B.; Brendel, Christian; Suerth, Julia D.; Mueller-Kuller, Uta; Chen-Wichmann, Linping; Schwäble, Joachim; Pahujani, Shweta; Kunkel, Hana; Schambach, Axel; Baum, Christopher; Grez, Manuel

2013-01-01

Comparative integrome analysis has revealed that the most neutral integration pattern among retroviruses is attributed to alpharetroviruses. We chose X-linked chronic granulomatous disease (X-CGD) as model to evaluate the potential of self-inactivating (SIN) alpharetroviral vectors for gene therapy of monogenic diseases. Therefore, we combined the alpharetroviral vector backbone with the elongation factor-1α short promoter, both considered to possess a low genotoxic profile, to drive transgene (gp91phox) expression. Following efficient transduction transgene expression was sustained and provided functional correction of the CGD phenotype in a cell line model at low vector copy number. Further analysis in a murine X-CGD transplantation model revealed gene-marking of bone marrow cells and oxidase positive granulocytes in peripheral blood. Transduction of human X-CGD CD34+ cells provided functional correction up to wild-type levels and long-term expression upon transplantation into a humanized mouse model. In contrast to lentiviral vectors, no aberrantly spliced transcripts containing cellular exons fused to alpharetroviral sequences were found in transduced cells, implying that the safety profile of alpharetroviral vectors may extend beyond their neutral integration profile. Taken together, this highlights the potential of this SIN alpharetroviral system as a platform for new candidate vectors for future gene therapy of hematopoietic disorders. PMID:23207695

Control of Current Profile and Instability by Radiofrequency Wave Injection in JT-60U and Its Applicability in JT-60SA

NASA Astrophysics Data System (ADS)

Isayama, A.; Suzuki, T.; Hayashi, N.; Ide, S.; Hamamatsu, K.; Fujita, T.; Hosoyama, H.; Kamada, Y.; Nagasaki, K.; Oyama, N.; Ozeki, T.; Sakata, S.; Seki, M.; Sueoka, M.; Takechi, M.; Urano, H.

2007-09-01

Recent results of control of current profile and instability using radiofrequency wave in JT-60U and prediction analysis in JT-60SA are descried. In JT-60U, control of current profile in high-beta regime was demonstrated by using a real-time system, where the motional Stark effect diagnostic and lower hybrid wave were used as a detector and actuator, respectively. The minimum value of the safety factor was raised from 1.3 to 1.7 so as to follow the commanded value. Complete stabilization of a neoclassical tearing mode (NTM) with the poloidal mode number m = 2 and the toroidal mode number n = 1 was demonstrated using electron cyclotron (EC) current drive. By scanning the location of EC current drive in detail, strong stabilization effect was found for misalignment less than about half of the full island width. In addition, destabilization of the 2/1 NTM was observed for misalignment comparable to the full island width. Simulation of NTM stabilization in JT-60SA was performed by using the TOPICS code combined with the modified Rutherford equation. The TOPICS simulation showed that complete stabilization can be achieved more effectively by optimizing the EC wave injection angle and modulating the EC wave.

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

Chrystal, C.; Grierson, B. A.; Staebler, G. M.

Here, experiments at the DIII-D tokamak have used dimensionless parameter scans to investigate the dependencies of intrinsic torque and momentum transport in order to inform a prediction of the rotation profile in ITER. Measurements of intrinsic torque profiles and momentum confinement time in dimensionless parameter scans of normalized gyroradius and collisionality are used to predict the amount of intrinsic rotation in the pedestal of ITER. Additional scans of T e/T i and safety factor are used to determine the accuracy of momentum flux predictions of the quasi-linear gyrokinetic code TGLF. In these scans, applications of modulated torque are used tomore » measure the incremental momentum diffusivity, and results are consistent with the E x B shear suppression of turbulent transport. These incremental transport measurements are also compared with the TGLF results. In order to form a prediction of the rotation profile for ITER, the pedestal prediction is used as a boundary condition to a simulation that uses TGLF to determine the transport in the core of the plasma. The predicted rotation is ≈20 krad/s in the core, lower than in many current tokamak operating scenarios. TGLF predictions show that this rotation is still significant enough to have a strong effect on confinement via E x B shear.« less

Predicting rotation for ITER via studies of intrinsic torque and momentum transport in DIII-D

DOE PAGES

Chrystal, C.; Grierson, B. A.; Staebler, G. M.; ...

2017-03-30

Here, experiments at the DIII-D tokamak have used dimensionless parameter scans to investigate the dependencies of intrinsic torque and momentum transport in order to inform a prediction of the rotation profile in ITER. Measurements of intrinsic torque profiles and momentum confinement time in dimensionless parameter scans of normalized gyroradius and collisionality are used to predict the amount of intrinsic rotation in the pedestal of ITER. Additional scans of T e/T i and safety factor are used to determine the accuracy of momentum flux predictions of the quasi-linear gyrokinetic code TGLF. In these scans, applications of modulated torque are used tomore » measure the incremental momentum diffusivity, and results are consistent with the E x B shear suppression of turbulent transport. These incremental transport measurements are also compared with the TGLF results. In order to form a prediction of the rotation profile for ITER, the pedestal prediction is used as a boundary condition to a simulation that uses TGLF to determine the transport in the core of the plasma. The predicted rotation is ≈20 krad/s in the core, lower than in many current tokamak operating scenarios. TGLF predictions show that this rotation is still significant enough to have a strong effect on confinement via E x B shear.« less

Control of Current Profile and Instability by Radiofrequency Wave Injection in JT-60U and Its Applicability in JT-60SA

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

Isayama, A.; Suzuki, T.; Hayashi, N.

2007-09-28

Recent results of control of current profile and instability using radiofrequency wave in JT-60U and prediction analysis in JT-60SA are descried. In JT-60U, control of current profile in high-beta regime was demonstrated by using a real-time system, where the motional Stark effect diagnostic and lower hybrid wave were used as a detector and actuator, respectively. The minimum value of the safety factor was raised from 1.3 to 1.7 so as to follow the commanded value. Complete stabilization of a neoclassical tearing mode (NTM) with the poloidal mode number m = 2 and the toroidal mode number n = 1 wasmore » demonstrated using electron cyclotron (EC) current drive. By scanning the location of EC current drive in detail, strong stabilization effect was found for misalignment less than about half of the full island width. In addition, destabilization of the 2/1 NTM was observed for misalignment comparable to the full island width. Simulation of NTM stabilization in JT-60SA was performed by using the TOPICS code combined with the modified Rutherford equation. The TOPICS simulation showed that complete stabilization can be achieved more effectively by optimizing the EC wave injection angle and modulating the EC wave.« less

A Twin Factor Mixture Modeling Approach to Childhood Temperament: Differential Heritability

PubMed Central

Scott, Brandon G.; Lemery-Chalfant, Kathryn; Clifford, Sierra; Tein, Jenn-Yun; Stoll, Ryan; Goldsmith, H. Hill

2016-01-01

Twin factor mixture modeling was used to identify temperament profiles, while simultaneously estimating a latent factor model for each profile with a sample of 787 twin pairs (Mage =7.4 years; SD = .84; 49% female; 88.3% Caucasian), using mother- and father-reported temperament. A 4-profile, 1-factor model fit the data well. Profiles included ‘Regulated, Typical Reactive’, ‘Well-regulated, Positive Reactive’, ‘Regulated, Surgent’, and ‘Dysregulated, Negative Reactive.’ All profiles were heritable, with heritability lower and shared environment also contributing to membership in the ‘Regulated, Typical Reactive’ and ‘Dysregulated, Negative Reactive’ profiles. PMID:27291568

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

PubMed

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

2016-08-01

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

Transport Barriers in Bootstrap Driven Tokamaks

NASA Astrophysics Data System (ADS)

Staebler, Gary

2017-10-01

Maximizing the bootstrap current in a tokamak, so that it drives a high fraction of the total current, reduces the external power required to drive current by other means. Improved energy confinement, relative to empirical scaling laws, enables a reactor to more fully take advantage of the bootstrap driven tokamak. Experiments have demonstrated improved energy confinement due to the spontaneous formation of an internal transport barrier in high bootstrap fraction discharges. Gyrokinetic analysis, and quasilinear predictive modeling, demonstrates that the observed transport barrier is due to the suppression of turbulence primarily due to the large Shafranov shift. ExB velocity shear does not play a significant role in the transport barrier due to the high safety factor. It will be shown, that the Shafranov shift can produce a bifurcation to improved confinement in regions of positive magnetic shear or a continuous reduction in transport for weak or negative magnetic shear. Operation at high safety factor lowers the pressure gradient threshold for the Shafranov shift driven barrier formation. The ion energy transport is reduced to neoclassical and electron energy and particle transport is reduced, but still turbulent, within the barrier. Deeper into the plasma, very large levels of electron transport are observed. The observed electron temperature profile is shown to be close to the threshold for the electron temperature gradient (ETG) mode. A large ETG driven energy transport is qualitatively consistent with recent multi-scale gyrokinetic simulations showing that reducing the ion scale turbulence can lead to large increase in the electron scale transport. A new saturation model for the quasilinear TGLF transport code, that fits these multi-scale gyrokinetic simulations, can match the data if the impact of zonal flow mixing on the ETG modes is reduced at high safety factor. This work was supported by the U.S. Department of Energy under DE-FG02-95ER54309 and DE-FC02-04ER54698.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors).

PubMed

Winthrop, K L; Mariette, X; Silva, J T; Benamu, E; Calabrese, L H; Dumusc, A; Smolen, J S; Aguado, J M; Fernández-Ruiz, M

2018-06-01

The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection. Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

PubMed

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I; Fischer, Kathelijn; Gill, Joan C; P'Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St Ledger, Katie; Pabinger, Ingrid

2016-08-04

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. © 2016 by The American Society of Hematology.

Teaching patient safety and human factors in undergraduate nursing curricula in England: a pilot survey.

PubMed

Robson, Wayne; Clark, Debbie; Pinnock, David; White, Nick; Baxendale, Bryn

Patient safety is a key priority for all healthcare systems, and there is growing recognition for the need to educate tomorrow's nurses about the role of human factors in reducing avoidable harm to patients. A pilot survey was sent to 20 schools of nursing in England to explore the teaching of patient safety and human factors. All 13 schools that responded (65% response rate) stated that patient safety was covered in their curricula and was allocated more than 4 hours; all the classes included human factors. Only two respondents indicated their teaching to be multi-professional. Awareness of the World Health Organization's multiprofessional patient safety curriculum guide was poor. Faculties also seemed unaware that the Institute for Healthcare Improvement provides free online patient safety modules for students and that there is a global network of student patient safety chapters.

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

PubMed

2010-09-29

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

Quasi-Static Probabilistic Structural Analyses Process and Criteria

NASA Technical Reports Server (NTRS)

Goldberg, B.; Verderaime, V.

1999-01-01

Current deterministic structural methods are easily applied to substructures and components, and analysts have built great design insights and confidence in them over the years. However, deterministic methods cannot support systems risk analyses, and it was recently reported that deterministic treatment of statistical data is inconsistent with error propagation laws that can result in unevenly conservative structural predictions. Assuming non-nal distributions and using statistical data formats throughout prevailing stress deterministic processes lead to a safety factor in statistical format, which integrated into the safety index, provides a safety factor and first order reliability relationship. The embedded safety factor in the safety index expression allows a historically based risk to be determined and verified over a variety of quasi-static metallic substructures consistent with the traditional safety factor methods and NASA Std. 5001 criteria.

Safety evaluation of trelagliptin in the treatment of Japanese type 2 diabetes mellitus patients.

PubMed

Kaku, Kohei

2017-11-01

Trelagliptin is a novel, long-acting dipeptidyl peptidase-4 (DPP-4) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM) in japan. The safety and efficacy of trelagliptin has been evaluated in three published clinical trials to date: one phase II and two phase III studies. As trelagliptin only requires dosing once per week, this new agent has the potential to improve compliance and subsequently, glycaemic control, in patients with T2DM. Areas covered: This article reviews the available safety data for trelagliptin from published clinical trials, and evaluates the published safety profile relative to competitor once-daily and once-weekly DPP-4 inhibitors. Expert opinion: Clinical trial data to date suggest that trelagliptin is a safe and efficacious medication with a similar safety profile to once-daily DPP-4 inhibitors, and to the once-weekly DPP-4 inhibitor, omarigliptin. Trelagliptin is well tolerated when given alone, and in combination with other anti-diabetic medications. An advantage of trelagliptin over existing once-daily DPP-4 inhibitors is the decrease of dosing frequency, rather than once-daily. No specific, serious adverse events have been reported for trelagliptin in published clinical trials, making it an attractive alternative to other DPP-4 inhibitors.

Patient safety in otolaryngology: a descriptive review.

PubMed

Danino, Julian; Muzaffar, Jameel; Metcalfe, Chris; Coulson, Chris

2017-03-01

Human evaluation and judgement may include errors that can have disastrous results. Within medicine and healthcare there has been slow progress towards major changes in safety. Healthcare lags behind other specialised industries, such as aviation and nuclear power, where there have been significant improvements in overall safety, especially in reducing risk of errors. Following several high profile cases in the USA during the 1990s, a report titled "To Err Is Human: Building a Safer Health System" was published. The report extrapolated that in the USA approximately 50,000 to 100,000 patients may die each year as a result of medical errors. Traditionally otolaryngology has always been regarded as a "safe specialty". A study in the USA in 2004 inferred that there may be 2600 cases of major morbidity and 165 deaths within the specialty. MEDLINE via PubMed interface was searched for English language articles published between 2000 and 2012. Each combined two or three of the keywords noted earlier. Limitations are related to several generic topics within patient safety in otolaryngology. Other areas covered have been current relevant topics due to recent interest or new advances in technology. There has been a heightened awareness within the healthcare community of patient safety; it has become a major priority. Focus has shifted from apportioning blame to prevention of the errors and implementation of patient safety mechanisms in healthcare delivery. Type of Errors can be divided into errors due to action and errors due to knowledge or planning. In healthcare there are several factors that may influence adverse events and patient safety. Although technology may improve patient safety, it also introduces new sources of error. The ability to work with people allows for the increase in safety netting. Team working has been shown to have a beneficial effect on patient safety. Any field of work involving human decision-making will always have a risk of error. Within Otolaryngology, although patient safety has evolved along similar themes as other surgical specialties; there are several specific high-risk areas. Medical error is a common problem and its human cost is of immense importance. Steps to reduce such errors require the identification of high-risk practice within a complex healthcare system. The commitment to patient safety and quality improvement in medicine depend on personal responsibility and professional accountability.

Analysis on Dangerous Source of Large Safety Accident in Storage Tank Area

NASA Astrophysics Data System (ADS)

Wang, Tong; Li, Ying; Xie, Tiansheng; Liu, Yu; Zhu, Xueyuan

2018-01-01

The difference between a large safety accident and a general accident is that the consequences of a large safety accident are particularly serious. To study the tank area which factors directly or indirectly lead to the occurrence of large-sized safety accidents. According to the three kinds of hazard source theory and the consequence cause analysis of the super safety accident, this paper analyzes the dangerous source of the super safety accident in the tank area from four aspects, such as energy source, large-sized safety accident reason, management missing, environmental impact Based on the analysis of three kinds of hazard sources and environmental analysis to derive the main risk factors and the AHP evaluation model is established, and after rigorous and scientific calculation, the weights of the related factors in four kinds of risk factors and each type of risk factors are obtained. The result of analytic hierarchy process shows that management reasons is the most important one, and then the environmental factors and the direct cause and Energy source. It should be noted that although the direct cause is relatively low overall importance, the direct cause of Failure of emergency measures and Failure of prevention and control facilities in greater weight.

Zero-profile implant versus conventional cage-plate implant in anterior cervical discectomy and fusion for the treatment of degenerative cervical spondylosis: a meta-analysis.

PubMed

Shao, Haiyu; Chen, Jinping; Ru, Bin; Yan, Feifei; Zhang, Jun; Xu, Shaonan; Huang, Yazeng

2015-09-17

Zero-profile implant has become more and more popular in anterior cervical discectomy and fusion (ACDF) for the treatment of degenerative cervical spondylosis. However, there was no enough evidence judging its efficiency and safety. The aim of this analysis was to evaluate the efficacy and safety of Zero-profile implant compared with conventional cage-plate (CCP) in ACDF. All studies directly comparing the outcomes between the Zero-profile implant and CCP implant in ACDF were included, and the search strategy followed the requirements of the Cochrane Library Handbook. Two of the authors extracted relevant data and checked the accuracy independently using standardized data collection form. Seven studies involving 560 patients were included, 262 in the Zero-profile group and 298 in the CCP group. Zero-profile implant had a lower rate of postoperative dysphagia at 2 weeks, 6 months, and 1 year (p = 0.0002, p = 0.008, and p = 0.001, respectively) than CCP implant. Zero-profile also reduced blood loss (p = 0.0001), while operation time and incidence of postoperative transient dysphagia had no statistical significance (p = 0.92, p = 0.42, respectively) between two groups. Based on the results of our analysis, the application of Zero-profile implant in ACDF had a lower rate of postoperative dysphagia at 2 weeks, 6 months, and 1 year than CCP implant. Zero-profile implant also had fewer blood loss during operation. More rigorous and adequately powered prospective randomized controlled trials with larger sample size are required to elucidate a more objective outcome.

2009 Human Factors and Roadway Safety Workshop : National Perspectives on Safety [SD .WMV (720x480/29fps/227.0 MB)

DOT National Transportation Integrated Search

2009-11-05

Iowa Department of Transportation Research and Technology Bureau video presentation from the 2009 human factors and roadway safety workshop session titled: National Perspectives on Safety : Essie Wagner, program analyst, National Highway Traffic Safe...

Safety climate in university and college laboratories: impact of organizational and individual factors.

PubMed

Wu, Tsung-Chih; Liu, Chi-Wei; Lu, Mu-Chen

2007-01-01

Universities and colleges serve to be institutions of education excellence; however, problems in the areas of occupational safety may undermine such goals. Occupational safety must be the concern of every employee in the organization, regardless of job position. Safety climate surveys have been suggested as important tools for measuring the effectiveness and improvement direction of safety programs. Thus, this study aims to investigate the influence of organizational and individual factors on safety climate in university and college laboratories. Employees at 100 universities and colleges in Taiwan were mailed a self-administered questionnaire survey; the response rate was 78%. Multivariate analysis of variance revealed that organizational category of ownership, the presence of a safety manager and safety committee, gender, age, title, accident experience, and safety training significantly affected the climate. Among them, accident experience and safety training affected the climate with practical significance. The authors recommend that managers should address important factors affecting safety issues and then create a positive climate by enforcing continuous improvements.

Profile: a computer program for displaying the geometric relationships of the responses in a factorial design

Treesearch

Stanford L. Arner

1974-01-01

One procedure in analyzing the responses to factors in an experiment is to construct profiles of the means. Profiles are plots of the sample means of each level of one factor at each level of one or more of the other factors in the experiment. The construction of these profiles and tests of hypotheses about the mean responses is called profile analysis. This paper...

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

PubMed Central

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

2017-01-01

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. PMID:28350366

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

PubMed

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.

Safety characteristics of the lithium SO2 system

NASA Technical Reports Server (NTRS)

Watson, T.

1978-01-01

Extensive tests were conducted to quantitatively define the safety characteristics of high-rate SO2 multicell batteries under various discharge and temperature profiles, which closely simulated actual field-use conditions. The resulting behavior patters of the multicell batteries and the corrective action which can be implemented to minimize or prevent hazardous battery performance are briefly summarized.

Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors.

PubMed

Naing, Aung; Papadopoulos, Kyriakos P; Autio, Karen A; Ott, Patrick A; Patel, Manish R; Wong, Deborah J; Falchook, Gerald S; Pant, Shubham; Whiteside, Melinda; Rasco, Drew R; Mumm, John B; Chan, Ivan H; Bendell, Johanna C; Bauer, Todd M; Colen, Rivka R; Hong, David S; Van Vlasselaer, Peter; Tannir, Nizar M; Oft, Martin; Infante, Jeffrey R

2016-10-10

Purpose Interleukin-10 (IL-10) stimulates the expansion and cytotoxicity of tumor-infiltrating CD8+ T cells and inhibits inflammatory CD4+ T cells. Pegylation prolongs the serum concentration of IL-10 without changing the immunologic profile. This phase I study sought to determine the safety and antitumor activity of AM0010. Patients and Methods Patients with selected advanced solid tumors were treated with AM0010 in a dose-escalation study, which was followed by a renal cell cancer (RCC) dose-expansion cohort. AM0010 was self-administered subcutaneously at doses of 1 to 40 μg/kg once per day. Primary end points were safety and tolerability; clinical activity and immune activation were secondary end points. Results In the dose-escalation and -expansion cohorts, 33 and 18 patients, respectively, were treated with daily subcutaneous injection of AM0010. AM0010 was tolerated in a heavily pretreated patient population. Treatment-related adverse events (AEs) included anemia, fatigue, thrombocytopenia, fever, and injection site reactions. Grade 3 to 4 nonhematopoietic treatment-related AEs, including rash (n = 2) and transaminitis (n = 1), were observed in five of 33 patients. Grade 3 to 4 anemia or thrombocytopenia was observed in five patients. Most treatment-related AEs were transient or reversible. AM0010 led to systemic immune activation with elevated immune-stimulatory cytokines and reduced transforming growth factor beta in the serum. Partial responses were observed in one patient with uveal melanoma and four of 15 evaluable patients with RCC treated at 20 μg/kg (overall response rate, 27%). Prolonged stable disease of at least 4 months was observed in four patients, including one with colorectal cancer with disease stabilization for 20 months. Conclusion AM0010 has an acceptable toxicity profile with early evidence of antitumor activity, particularly in RCC. These data support the further evaluation of AM0010 both alone and in combination with other immune therapies and chemotherapies.

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib.

PubMed

Kawalec, Paweł; Śladowska, Katarzyna; Malinowska-Lipień, Iwona; Brzostek, Tomasz; Kózka, Maria

2018-01-01

Xeljanz ® (tofacitinib) is an oral small-molecule inhibitor that reversibly inhibits Janus-activated kinase (JAK)-dependent cytokine signaling, thus reducing inflammation. As a result of these mechanisms, effects on the immune system such as a moderate decrease in the total lymphocyte count, a dose-dependent decrease in natural killer (NK) cell count, and an increase in B-cell count have been observed. Therefore, tofacitinib provides an innovative approach to modulating the immune and inflammatory responses in patients with rheumatoid arthritis (RA), which is especially important in individuals who do not respond to tumor necrosis factor inhibitors or show a loss of response over time. The aim of this article was to review studies on the pharmacology, mode of action, pharmacokinetics, efficacy, and safety of tofacitinib in patients with RA. Tofacitinib has been shown to reduce symptoms of RA and improve the quality of life in the analyzed groups of patients. Moreover, it showed high efficacy and an acceptable safety profile in Phase III randomized clinical trials on RA and was the first JAK inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in the RA therapy, thus providing a useful alternative treatment strategy. Randomized controlled studies revealed a significant benefit over placebo in efficacy outcomes (American College of Rheumatology [ACR] 20 and ACR50 response rates); accordingly, clinically meaningful improvements in patient-related outcomes compared with placebo have been reported. The safety profile seems acceptable, although some severe adverse effects have been observed, including serious infections, opportunistic infections (including tuberculosis and herpes zoster), malignancies, and cardiovascular events, which require strict monitoring irrespective of the duration of tofacitinib administration. As an oral drug, tofacitinib offers an alternative to subcutaneous or intravenous biologic drugs and should be recognized as a more convenient way of drug administration.

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib

PubMed Central

Kawalec, Paweł; Śladowska, Katarzyna; Malinowska-Lipień, Iwona; Brzostek, Tomasz; Kózka, Maria

2018-01-01

Xeljanz® (tofacitinib) is an oral small-molecule inhibitor that reversibly inhibits Janus-activated kinase (JAK)-dependent cytokine signaling, thus reducing inflammation. As a result of these mechanisms, effects on the immune system such as a moderate decrease in the total lymphocyte count, a dose-dependent decrease in natural killer (NK) cell count, and an increase in B-cell count have been observed. Therefore, tofacitinib provides an innovative approach to modulating the immune and inflammatory responses in patients with rheumatoid arthritis (RA), which is especially important in individuals who do not respond to tumor necrosis factor inhibitors or show a loss of response over time. The aim of this article was to review studies on the pharmacology, mode of action, pharmacokinetics, efficacy, and safety of tofacitinib in patients with RA. Tofacitinib has been shown to reduce symptoms of RA and improve the quality of life in the analyzed groups of patients. Moreover, it showed high efficacy and an acceptable safety profile in Phase III randomized clinical trials on RA and was the first JAK inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in the RA therapy, thus providing a useful alternative treatment strategy. Randomized controlled studies revealed a significant benefit over placebo in efficacy outcomes (American College of Rheumatology [ACR] 20 and ACR50 response rates); accordingly, clinically meaningful improvements in patient-related outcomes compared with placebo have been reported. The safety profile seems acceptable, although some severe adverse effects have been observed, including serious infections, opportunistic infections (including tuberculosis and herpes zoster), malignancies, and cardiovascular events, which require strict monitoring irrespective of the duration of tofacitinib administration. As an oral drug, tofacitinib offers an alternative to subcutaneous or intravenous biologic drugs and should be recognized as a more convenient way of drug administration. PMID:29317823

Development of an evidence-based framework of factors contributing to patient safety incidents in hospital settings: a systematic review

PubMed Central

McEachan, Rosemary R C; Giles, Sally J; Sirriyeh, Reema; Watt, Ian S; Wright, John

2012-01-01

Objective The aim of this systematic review was to develop a ‘contributory factors framework’ from a synthesis of empirical work which summarises factors contributing to patient safety incidents in hospital settings. Design A mixed-methods systematic review of the literature was conducted. Data sources Electronic databases (Medline, PsycInfo, ISI Web of knowledge, CINAHL and EMBASE), article reference lists, patient safety websites, registered study databases and author contacts. Eligibility criteria Studies were included that reported data from primary research in secondary care aiming to identify the contributory factors to error or threats to patient safety. Results 1502 potential articles were identified. 95 papers (representing 83 studies) which met the inclusion criteria were included, and 1676 contributory factors extracted. Initial coding of contributory factors by two independent reviewers resulted in 20 domains (eg, team factors, supervision and leadership). Each contributory factor was then coded by two reviewers to one of these 20 domains. The majority of studies identified active failures (errors and violations) as factors contributing to patient safety incidents. Individual factors, communication, and equipment and supplies were the other most frequently reported factors within the existing evidence base. Conclusions This review has culminated in an empirically based framework of the factors contributing to patient safety incidents. This framework has the potential to be applied across hospital settings to improve the identification and prevention of factors that cause harm to patients. PMID:22421911

Balancing Selectivity and Efficacy of Bispecific Epidermal Growth Factor Receptor (EGFR) × c-MET Antibodies and Antibody-Drug Conjugates*

PubMed Central

Sellmann, Carolin; Doerner, Achim; Knuehl, Christine; Rasche, Nicolas; Sood, Vanita; Krah, Simon; Rhiel, Laura; Messemer, Annika; Wesolowski, John; Schuette, Mark; Becker, Stefan; Toleikis, Lars; Kolmar, Harald; Hock, Bjoern

2016-01-01

Bispecific antibodies (bsAbs) and antibody-drug conjugates (ADCs) have already demonstrated benefits for the treatment of cancer in several clinical studies, showing improved drug selectivity and efficacy. In particular, simultaneous targeting of prominent cancer antigens, such as EGF receptor (EGFR) and c-MET, by bsAbs has raised increasing interest for potentially circumventing receptor cross-talk and c-MET-mediated acquired resistance during anti-EGFR monotherapy. In this study, we combined the selectivity of EGFR × c-MET bsAbs with the potency of cytotoxic agents via bispecific antibody-toxin conjugation. Affinity-attenuated bispecific EGFR × c-MET antibody-drug conjugates demonstrated high in vitro selectivity toward tumor cells overexpressing both antigens and potent anti-tumor efficacy. Due to basal EGFR expression in the skin, ADCs targeting EGFR in general warrant early safety assessments. Reduction in EGFR affinity led to decreased toxicity in keratinocytes. Thus, the combination of bsAb affinity engineering with the concept of toxin conjugation may be a viable route to improve the safety profile of ADCs targeting ubiquitously expressed antigens. PMID:27694443

Emerging Treatment Options in Mild to Moderate Ulcerative Colitis

PubMed Central

Lichtenstein, Gary R.; Hanauer, Stephen B.; Sandborn, William J.

2015-01-01

Ulcerative colitis (UC) is a chronic inflammatory condition associated with rectal bleeding and urgency, tenesmus, and diarrhea. Several medical therapies can be used in the treatment of UC. Aminosalicylates are widely used based on their efficacy in the induction and maintenance of remission. Although corticosteroids are effective in patients with more severe disease, systemic use is associated with significant safety concerns. The newer corticosteroid budesonide has lower systemic bioavailability and, consequently, a more favorable safety profile. A budesonide extended-release formulation allows once-daily dosing and delivers the agent locally throughout the colon. Biologic agents used for the treatment of moderate to severe UC include the tumor necrosis factor inhibitors infliximab, adalimumab, and golimumab, and the integrin inhibitor vedolizumab. Rectally administered therapy can also be useful in the treatment of UC. In October 2014, the US Food and Drug Administration approved a budesonide foam formulation for inducing remission in patients with active mild to moderate distal UC extending up to 40 cm from the anal verge. Budesonide foam rapidly distributes to the sigmoid colon and the rectum and avoids some of the drawbacks of suppositories and enemas. PMID:26491415

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

PubMed

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.

Scientific evaluation of the safety factor for the acceptable daily intake (ADI). Case study: butylated hydroxyanisole (BHA).

PubMed

Würtzen, G

1993-01-01

The principles of 'data-derived safety factors' are applied to toxicological and biochemical information on butylated hydroxyanisole (BHA). The calculated safety factor for an ADI is, by this method, comparable to the existing internationally recognized safety evaluations. Relevance for humans of forestomach tumours in rodents is discussed. The method provides a basis for organizing data in a way that permits an explicit assessment of its relevance.

Identifying at-risk profiles and protective factors for problem gambling: A longitudinal study across adolescence and early adulthood.

PubMed

Allami, Youssef; Vitaro, Frank; Brendgen, Mara; Carbonneau, René; Tremblay, Richard E

2018-05-01

Past studies have identified various risk and protective factors for problem gambling (PG). However, no study has examined the interplay between these factors using a combination of person-centered and variable-centered approaches embedded within a longitudinal design. The present study aimed to (a) identify distinct profiles in early adolescence based on a set of risk factors commonly associated with PG (impulsivity, depression, anxiety, drug-alcohol use, aggressiveness, and antisociality), (b) explore the difference in reported gambling problems between these profiles during midadolescence and early adulthood, and (c) identify family- and peer-related variables that could operate as protective or compensatory factors in this context. Two samples were used: (a) a population sample (N = 1,033) living in low socioeconomic-status neighborhoods and (b) a population sample (N = 3,017) representative of students attending Quebec schools. Latent profile analyses were conducted to identify at-risk profiles based on individual risk factors measured at age 12 years. Negative binomial regression models were estimated to compare profiles in terms of their reported gambling problems at ages 16 and 23. Finally, family- and peer-related variables measured at age 14 were included to test their protective or compensatory role with respect to the link between at-risk profiles and gambling problems. Four profiles were identified: well-adjusted, internalizing, externalizing, and comorbid. Compared to the well-adjusted profile, the externalizing and comorbid profiles reported more gambling problems at ages 16 and 23, but the internalizing profile did not differ significantly. Various protective and compensatory factors emerged for each profile at both time points. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Numerical Solution of the Electron Heat Transport Equation and Physics-Constrained Modeling of the Thermal Conductivity via Sequential Quadratic Programming Optimization in Nuclear Fusion Plasmas

NASA Astrophysics Data System (ADS)

Paloma, Cynthia S.

The plasma electron temperature (Te) plays a critical role in a tokamak nu- clear fusion reactor since temperatures on the order of 108K are required to achieve fusion conditions. Many plasma properties in a tokamak nuclear fusion reactor are modeled by partial differential equations (PDE's) because they depend not only on time but also on space. In particular, the dynamics of the electron temperature is governed by a PDE referred to as the Electron Heat Transport Equation (EHTE). In this work, a numerical method is developed to solve the EHTE based on a custom finite-difference technique. The solution of the EHTE is compared to temperature profiles obtained by using TRANSP, a sophisticated plasma transport code, for specific discharges from the DIII-D tokamak, located at the DIII-D National Fusion Facility in San Diego, CA. The thermal conductivity (also called thermal diffusivity) of the electrons (Xe) is a plasma parameter that plays a critical role in the EHTE since it indicates how the electron temperature diffusion varies across the minor effective radius of the tokamak. TRANSP approximates Xe through a curve-fitting technique to match experimentally measured electron temperature profiles. While complex physics-based model have been proposed for Xe, there is a lack of a simple mathematical model for the thermal diffusivity that could be used for control design. In this work, a model for Xe is proposed based on a scaling law involving key plasma variables such as the electron temperature (Te), the electron density (ne), and the safety factor (q). An optimization algorithm is developed based on the Sequential Quadratic Programming (SQP) technique to optimize the scaling factors appearing in the proposed model so that the predicted electron temperature and magnetic flux profiles match predefined target profiles in the best possible way. A simulation study summarizing the outcomes of the optimization procedure is presented to illustrate the potential of the proposed modeling method.

Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects

PubMed Central

Frost, Charles; Nepal, Sunil; Wang, Jessie; Schuster, Alan; Byon, Wonkyung; Boyd, Rebecca A; Yu, Zhigang; Shenker, Andrew; Barrett, Yu Chen; Mosqueda-Garcia, Rogelio; LaCreta, Frank

2013-01-01

Aim Apixaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and under development for treatment of venous thromboembolism. This study examined the safety, pharmacokinetics and pharmacodynamics of multiple dose apixaban. Method This double-blind, randomized, placebo-controlled, parallel group, multiple dose escalation study was conducted in six sequential dose panels – apixaban 2.5, 5, 10 and 25 mg twice daily and 10 and 25 mg once daily– with eight healthy subjects per panel. Within each panel, subjects were randomized (3:1) to oral apixaban or placebo for 7 days. Subjects underwent safety assessments and were monitored for adverse events (AEs). Blood samples were taken to measure apixaban plasma concentration, international normalized ratio (INR), activated partial thromboplastin time (aPTT) and modified prothrombin time (mPT). Results Forty-eight subjects were randomized and treated (apixaban, n = 36; placebo, n = 12); one subject receiving 2.5 mg twice daily discontinued due to AEs (headache and nausea). No dose limiting AEs were observed. Apixaban maximum plasma concentration was achieved ∼3 h post-dose. Exposure increased approximately in proportion to dose. Apixaban steady-state concentrations were reached by day 3, with an accumulation index of 1.3–1.9. Peak : trough ratios were lower for twice daily vs. once daily regimens. Clotting times showed dose-related increases tracking the plasma concentration–time profile. Conclusion Multiple oral doses of apixaban were safe and well tolerated over a 10-fold dose range, with pharmacokinetics with low variability and concentration-related increases in clotting time measures. PMID:23451769

A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis.

PubMed

Sánchez, Mikel; Fiz, Nicolás; Azofra, Juan; Usabiaga, Jaime; Aduriz Recalde, Enmanuel; Garcia Gutierrez, Antonio; Albillos, Javier; Gárate, Ramón; Aguirre, Jose Javier; Padilla, Sabino; Orive, Gorka; Anitua, Eduardo

2012-08-01

This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee pain from osteoarthritis. We randomly assigned 176 patients with symptomatic knee osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis). The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As secondary outcomes, we also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety. The mean age of the patients was 59.8 years, and 52% were women. Compared with the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher (95% confidence interval, 0.5 to 27.6; P = .044). Regarding the secondary outcome measures, the rate of response to PRGF-Endoret was higher in all cases, although no significant differences were reached. Adverse events were mild and evenly distributed between the groups. Plasma rich in growth factors showed superior short-term results when compared with HA in a randomized controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate osteoarthritis of the knee. Level I, randomized controlled multicenter trial. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheumatoid arthritis.

PubMed

Dokoupilová, E; Aelion, J; Takeuchi, T; Malavolta, N; Sfikakis, P P; Wang, Y; Rohrer, S; Richards, H B

2018-02-20

To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.

Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a long-term, prospective real-life study.

PubMed

Vassilopoulos, Dimitrios; Delicha, Evie M; Settas, Loukas; Andrianakos, Alexandros; Aslanidis, Spyros; Boura, Panagiota; Katsounaros, Marios; Athanassiou, Panagiotis; Tempos, Konstantinos; Skarantavos, Grigorios; Antoniadis, Christodoulos; Papazoglou, Sotirios; Sakkas, Lazaros; Galanopoulou, Vassiliki; Skopouli, Fotini; Boki, Kyriaki; Daoussis, Dimitrios; Vritzali, Eleni; Sfikakis, Petros P

2016-01-01

To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice. This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months. 234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy. Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.

Immunogenicity and safety of two doses of a non-adjuvanted influenza A H1N1/2009 vaccine in young autoimmune rheumatic diseases patients.

PubMed

Aikawa, N E; Trudes, G; Campos, L M A; Pereira, R M R; Moraes, J C B; Ribeiro, A C; Miraglia, J; Timenetsky, M do Carmo S; Bonfa, E; Silva, Ca

2013-11-01

The aim of this study was to evaluate the immunogenicity and safety of the influenza A H1N1/2009 vaccine in children under 9 years old with autoimmune rheumatic diseases (ARD). Thirty-eight ARD patients and 11 healthy children received two doses of non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like vaccine. Subjects were evaluated before and 21 days after vaccination. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers (GMT) and factor increases (FI) in GMT were calculated. Mean ages were comparable between patients and controls. Pre-vaccination SP and GMT were similar in patients and controls (p > 0.05). Three weeks after immunization, SP (81.6% vs. 81.8%, p = 1.0), SC (81.6% vs. 90.9%, p = 0.66), GMT (151.5 vs. 282.1, p = 0.26) and the FI in GMT (16.7 vs. 36.3, p = 0.23) were similar in patients and controls, with both groups achieving an adequate response, according to the European Medicines Agency and Food and Drug Administration standards. Analysis of the possible factors influencing SC showed no difference in demographic data, leukocyte/lymphocyte counts or immunosuppressant use between seroconverted and non-seroconverted patients (p > 0.05). The vaccine demonstrated a satisfactory safety profile in this population. Two doses of influenza A H1N1/2009 vaccination induced an effective antibody response and caused adverse events in rare instances, suggesting this vaccine is appropriate and can be recommended for this age group.

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors).

PubMed

Reinwald, M; Silva, J T; Mueller, N J; Fortún, J; Garzoni, C; de Fijter, J W; Fernández-Ruiz, M; Grossi, P; Aguado, J M

2018-06-01

The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the reviewed agents. Copyright © 2018. Published by Elsevier Ltd.

Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

PubMed

Schubert, R; Eickmeier, O; Garn, H; Baer, P C; Mueller, T; Schulze, J; Rose, M A; Rosewich, M; Renz, H; Zielen, S

2009-01-01

Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p < 0.001) and specific IgG4(Mite) (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients. (c) 2008 S. Karger AG, Basel.

Ferulic acid photoprotective properties in association with UV filters: multifunctional sunscreen with improved SPF and UVA-PF.

PubMed

Peres, Daniela D'Almeida; Sarruf, Fernanda Daud; de Oliveira, Camila Areias; Velasco, Maria Valéria Robles; Baby, André Rolim

2018-05-26

Ultraviolet (UV) radiation stimulates several injurious biological effects on cutaneous tissue, causing, for instance, photocarcinogenesis. Sunscreens are topical products designed to protect the skin against these harmful effects and their use must be encouraged. The addition of antioxidants, as ferulic acid (FA), a phenolic compound from the class of the hydroxycinnamic acids, in sunscreens could improve their sun protection factor (SPF) and prevent inflammatory reactions. Here, the clinical safety and efficacy of an association of ethylhexyl triazone and bis-ethylhexyloxyphenol methoxyphenyl triazine (UV filters) with ferulic acid were assessed. Samples had good skin biocompatibility and presented satisfactory safety profile, even in a sun-exposed condition. A synergic effect between the natural polyphenol and the UV filters was evidenced, as well as, FA increased in vivo SPF in 37% and the UVA protection factor (UVA-PF) in 26%. The in vivo data indicated that FA reinforced the broad-spectrum characteristic of the photoprotective formulations. Additionally, according to the results from the ex vivo antioxidant test, it is plausible to recommend adjustments on the ex vivo protocol to explicitly determine the positive effects of topical antioxidant ingredients applied over the skin. These results provided a new perspective for the development of multifunctional bioactive sunscreens using FA as a new platform. Copyright © 2018 Elsevier B.V. All rights reserved.

Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.

PubMed

Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Myasoedova, Veronika; Amato, Manuela; Ventre, Itala; Tremoli, Elena; Minno, Alessandro Di

2017-01-01

In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recombinant granulocyte colony-stimulating factor (rG-CSF) in the management of neutropenia induced by anthracyclines and ifosfamide in patients with soft tissue sarcomas (NEUSAR).

PubMed

Bongiovanni, Alberto; Monti, Manuela; Foca, Flavia; Recine, Federica; Riva, Nada; Di Iorio, Valentina; Liverani, Chiara; De Vita, Alessandro; Miserocchi, Giacomo; Mercatali, Laura; Amadori, Dino; Ibrahim, Toni

2017-01-01

Anthracycline and ifosfamide-based chemotherapy represents a widely used regimen both in early and advanced settings in soft tissue sarcoma (STS). Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the severity of chemotherapy-induced neutropenia. The aim of this study was to assess the efficacy and safety of biosimilar G-CSF in these patients. Between 2003 and 2013, 67 patients with soft tissue tumors under epirubicin and ifosfamide (EI) treatment receiving biosimilar filgrastim (Zarzio®), originator filgrastim (Granulokine®, Neupogen®), and lenograstim (only originator Myelostim®) as primary prophylaxis for a total of 260 cycles of therapy were retrospectively analyzed. Baseline patient characteristics were summarized in a propensity score (PS). The incidence of febrile neutropenia (FN) was 44.0 % in biosimilar filgrastim, 40.0 % in originator filgrastim, and 45.5 % in the lenograstim groups (p = 0.935). All grade and G4 neutropenia were similar in the three groups with the same safety profile. The use of biosimilar filgrastim achieved cost savings of €225.25 over originator filgrastim and €262.00 over lenograstim. Biosimilar G-CSF was effective in preventing FN and in reducing the need for hospitalization in STS patients undergoing EI treatment. It also proved comparable to its reference products from both a clinical and cost-effective standpoint.

National surveillance of Salmonella Enteritidis in commercial eggs in Japan.

PubMed

Esaki, H; Shimura, K; Yamazaki, Y; Eguchi, M; Nakamura, M

2013-05-01

A total of 105 033 eggs were collected across Japan from June 2010 to January 2011 and tested for Salmonella Enteritidis to provide data for the risk profiling of S. Enteritidis in eggs by the Food Safety Commission of Japan. S. Enteritidis isolates were recovered from three samples (20 eggs/sample) and these samples were different in regard to sampling period, grading and packaging centre and farm. The prevalence of S. Enteritidis in commercial eggs in Japan is estimated at ~0.003% which was a tenfold decrease in prevalence compared to similar surveillance in the mid 1990s. The decrease in the contamination in commercial eggs is considered a contributory factor in the decrease of foodborne diseases associated with S. Enteritidis in this period.

Improving fast-ion confinement in high-performance discharges by suppressing Alfvén eigenmodes

DOE PAGES

Kramer, Geritt J.; Podestà, Mario; Holcomb, Christopher; ...

2017-03-28

Here, we show that the degradation of fast-ion confinement in steady-state DIII-D discharges is quantitatively consistent with predictions based on the effects of multiple unstable Alfven eigenmodes on beam-ion transport. Simulation and experiment show that increasing the radius where the magnetic safety factor has its minimum is effective in minimizing beam-ion transport. This is favorable for achieving high performance steady-state operation in DIII-D and future reactors. A comparison between the experiments and a critical gradient model, in which only equilibrium profiles were used to predict the most unstable modes, show that in a number of cases this model reproduces themore » measured neutron rate well.« less

Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.

PubMed

Skalski, Joseph H; Kern, Ryan M; Midthun, David E; Edell, Eric S; Maldonado, Fabien

2016-01-01

We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.

Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study.

PubMed

Park, Won; Lee, Sang Joon; Yun, Jihye; Yoo, Dae Hyun

2015-01-01

To compare the pharmacokinetics (PK), safety and tolerability of biosimilar infliximab (CT-P13 [Remsima(®), Inflectra(®)]) with two formulations of the reference medicinal product (RMP) (Remicade(®)) from either Europe (EU-RMP) or the USA (US-RMP). This was a double-blind, three-arm, parallel-group study (EudraCT number: 2013-003173-10). Healthy subjects received single doses (5 mg/kg) of CT-P13 (n = 71), EU-RMP (n = 71) or US-RMP (n = 71). The primary objective was to compare the PK profiles for the three formulations. Assessments of comparative safety and tolerability were secondary objectives. Baseline demographics were well balanced across the three groups. Primary end points (Cmax, AUClast and AUCinf) were equivalent between all formulations (CT-P13 vs EU-RMP; CT-P13 vs US-RMP; EU-RMP vs US-RMP). All other PK end points supported the high similarity of the three treatments. Tolerability profiles of the formulations were similar. The PK profile of CT-P13 is highly similar to EU-RMP and US-RMP. All three formulations were equally well tolerated.

The Role of Mifepristone in Meningiomas Management: A Systematic Review of the Literature.

PubMed

Cossu, Giulia; Levivier, Marc; Daniel, Roy Thomas; Messerer, Mahmoud

2015-01-01

We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients. A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014. Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition. A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered. No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients' selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required.

Brexpiprazole: A Partial Dopamine Agonist for the Treatment of Schizophrenia.

PubMed

Ekinci, Asli; Ekinci, Okan

2018-01-31

Schizophrenia is a chronic and debilitating mental disorder that affects the patient's and their family's life. The disease remains a complicated disorder that is challenging to treat, despite there being a large antipsychotic armamentarium. Brexpiprazole acts both as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at the serotonin 5- HT2A and noradrenaline alpha1B and alpha2C receptors, all with similar potency. This balanced receptor profile may produce promising antipsychotic effects on positive, negative and cognitive symptoms in schizophrenia with minimal adverse effects. This review summarizes the pharmacodynamics and pharmacokinetic profile of brexpiprazole and the clinical trial information pertaining to its effectiveness and safety and tolerability, discusses its best clinical use, and compares its clinical profile to those of other widely used antipsychotic agents. Brexpiprazole demonstrated significant clinical efficacy and had good safety and tolerability in well-designed trials with patients with schizophrenia. This agent may be a useful treatment alternative. However, it will be valuable to consider a long-term observational study that includes an active comparator, especially other second-generation antipsychotics (SGAs), to further evaluate the efficacy and safety of brexpiprazole in the treatment of schizophrenia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study).

PubMed

Kinugawa, Koichiro; Inomata, Takayuki; Sato, Naoki; Yasuda, Moriyoshi; Shimakawa, Toshiyuki; Bando, Kosuke; Mizuguchi, Kazuki

2015-01-01

The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < 80 years (U-80). The results showed that the effectiveness of tolvaptan in the aged patients was similar to that in U-80 patients. In the safety profile, the incidence rate of thirst was lower in the aged patients than that in U-80 patients (9.6% versus 11.6%, P = 0.0023). Furthermore, the incidence of hypernatremia, defined as ≥ 150 mEq/L in aged patients, was comparable with that in U-80 patients (2.9% versus 3.6%, respectively, P = 0.3657). Based on these findings, tolvaptan has similar effectiveness and safety profiles in aged patients compared with U-80 patients. In addition, we found that a higher starting dose of tolvaptan was markedly associated with the occurrence of hypernatremia exclusively in the aged population; therefore, we recommend that tolvaptan should be started at lower doses in aged patients.

Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review.

PubMed

Benoit, Eric; O'Donnell, Thomas F; Patel, Amit N

2013-01-01

Researchers have accumulated a decade of experience with autologous cell therapy in the treatment of critical limb ischemia (CLI). We conducted a systematic review of clinical trials in the literature to determine the safety and efficacy of cell therapy in CLI. We searched the literature for clinical trials of autologous cell therapy in CLI, including observational series of five or more patients to accrue a large pool of patients for safety analysis. Safety analysis included evaluation of death, cancer, unregulated angiogenesis, and procedural adverse events such as bleeding. Efficacy analysis included the clinical endpoints amputation and death as well as functional and surrogate endpoints. We identified 45 clinical trials, including seven RCTs, and 1,272 patients who received cell therapy. The overall adverse event rate was low (4.2%). Cell therapy patients did not have a higher mortality rate than control patients and demonstrated no increase in cancer incidence when analyzed against population rates. With regard to efficacy, cell therapy patients had a significantly lower amputation rate than control patients (OR 0.36, p = 0.0004). Cell therapy also demonstrated efficacy in a variety of functional and surrogate outcomes. Clinical trials differed in the proportion of patients with risk factors for clinical outcomes, and these influenced rates of amputation and death. Cell therapy presents a favorable safety profile with a low adverse event rate and no increase in severe events such as mortality and cancer and treatment with cell therapy decreases the risk of amputation. Cell therapy has a positive benefit-to-risk ratio in CLI and may be a valuable treatment option, particularly for those challenging patients who cannot undergo arterial reconstruction.

Lifestyle and accidents among young drivers.

PubMed

Gregersen, N P; Berg, H Y

1994-06-01

This study covers the lifestyle component of the problems related to young drivers' accident risk. The purpose of the study is to measure the relationship between lifestyle and accident risk, and to identify specific high-risk and low-risk groups. Lifestyle is measured through a questionnaire, where 20-year-olds describe themselves and how often they deal with a large number of different activities, like sports, music, movies, reading, cars and driving, political engagement, etc. They also report their involvement in traffic accidents. With a principal component analysis followed by a cluster analysis, lifestyle profiles are defined. These profiles are finally correlated to accidents, which makes it possible to define high-risk and low-risk groups. The cluster analysis defined 15 clusters including four high-risk groups with an average overrisk of 150% and two low-risk groups with an average underrisk of 75%. The results are discussed from two perspectives. The first is the importance of theoretical understanding of the contribution of lifestyle factors to young drivers' high accident risk. The second is how the findings could be used in practical road safety measures, like education, campaigns, etc.

Current profile redistribution driven by neutral beam injection in a reversed-field pinch

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

Parke, E.; Department of Physics, University of Wisconsin-Madison 1150 University Ave., Madison, Wisconsin 53706; Anderson, J. K.

2016-05-15

Neutral beam injection in reversed-field pinch (RFP) plasmas on the Madison Symmetric Torus [Dexter et al., Fusion Sci. Technol. 19, 131 (1991)] drives current redistribution with increased on-axis current density but negligible net current drive. Internal fluctuations correlated with tearing modes are observed on multiple diagnostics; the behavior of tearing mode correlated structures is consistent with flattening of the safety factor profile. The first application of a parametrized model for island flattening to temperature fluctuations in an RFP allows inferrence of rational surface locations for multiple tearing modes. The m = 1, n = 6 mode is observed to shift inward by 1.1 ± 0.6 cm withmore » neutral beam injection. Tearing mode rational surface measurements provide a strong constraint for equilibrium reconstruction, with an estimated reduction of q{sub 0} by 5% and an increase in on-axis current density of 8% ± 5%. The inferred on-axis current drive is consistent with estimates of fast ion density using TRANSP [Goldston et al., J. Comput. Phys. 43, 61 (1981)].« less

Carbon microgranule injection into NSTX-U discharges for edge diagnostic research

NASA Astrophysics Data System (ADS)

Lunsford, Robert; Roquemore, A. Lane; Scotti, Filippo; Mansfield, Dennis; Bortolon, Alessandro; Kaita, Robert; Maingi, Rajesh

2016-10-01

Microgranule injection is a versatile means for investigating edge plasmas in fusion devices. Employing a dual bladed rotary turbine, carbon microgranules ranging in diameter from 300 - 700 microns are radially injected into NSTX-U discharges at approximately 50 m/sec. Utilizing multiple high speed camera views, a 3D reconstruction of the injection geometry is created which characterizes the ablation rate and granule trajectory. By coupling this with a neutral gas shielding (NGS) ablation model, the granule mass deposition profile can be determined. Simulation projects a depositional barycenter near the pedestal shoulder for H-mode discharges, and 20 cm inboard of the LCFS for L-mode discharges. Spectroscopic measurements of this localized particle source can be used to characterize impurity transport within the discharge, and potentially allows for direct measurement of the safety factor profile (q). In addition, the transient pressure peaking resultant from injection into H-mode plasmas can also result in the prompt triggering of an edge localized mode (ELM). Work supported by DOE Contract No. DE-AC02-09CH11466.

M3D-K Simulations of Beam-Driven Alfven Eigenmodes in ASDEX-U

NASA Astrophysics Data System (ADS)

Wang, Ge; Fu, Guoyong; Lauber, Philipp; Schneller, Mirjam

2013-10-01

Core-localized Alfven eigenmodes are often observed in neutral beam-heated plasma in ASDEX-U tokamak. In this work, hybrid simulations with the global kinetic/MHD hybrid code M3D-K have been carried out to investigate the linear stability and nonlinear dynamics of beam-driven Alfven eigenmodes using experimental parameters and profiles of an ASDEX-U discharge. The safety factor q profile is weakly reversed with minimum q value about qmin = 3.0. The simulation results show that the n = 3 mode transits from a reversed shear Alfven eigenmode (RSAE) to a core-localized toroidal Alfven eigenmode (TAE) as qmin drops from 3.0 to 2.79, consistent with results from the stability code NOVA as well as the experimental measurement. The M3D-K results are being compared with those of the linear gyrokinetic stability code LIGKA for benchmark. The simulation results will also be compared with the measured mode frequency and mode structure. This work was funded by the Max-Planck/Princeton Center for Plasma Physics.

LY3127760, a Selective Prostaglandin E4 (EP4) Receptor Antagonist, and Celecoxib: A Comparison of Pharmacological Profiles

PubMed Central

Smith, Claire; Hu, Leijun; Coutant, David E.; Whitehurst, Kelly; Phipps, Krista; McNearney, Terry Ann; Yang, Xiao; Ackermann, Bradley; Pottanat, Thomas; Landschulz, William

2017-01-01

Abstract Safety, tolerability, and pharmacology profiles of LY3127760, an EP4 antagonist, were explored in healthy subjects in a subject/investigator‐blind, parallel‐group, multiple‐ascending dose study. Cohorts consisted of 13 patients randomized to LY3127760, celecoxib (400 mg), or placebo (9:2:2 ratio) for 28 days. LY3127760 was well tolerated; the most commonly observed adverse events were gastrointestinal, similar to celecoxib. LY3127760 increased release of ex vivo tumor necrosis factor alpha after lipopolysaccharide/prostaglandin E2 stimulation when compared with placebo, suggesting a dose‐dependent blockade of the EP4 receptor. Compared with placebo, 24‐h urinary excretion of prostaglandin E metabolite was modestly increased; prostacyclin metabolite was inhibited; and thromboxane A2 metabolite was unchanged. Effects on sodium and potassium excretion were similar to those of celecoxib. We conclude that LY3127760 demonstrated similar effects on prostacyclin synthesis and renal sodium retention as celecoxib. These data support exploration of LY3127760 at daily doses of 60 mg to 600 mg in phase II trials. This trial's registration number: NCT01968070. PMID:28857461

Tokamak Equilibrium Reconstruction with MSE-LS Data in DIII-D

NASA Astrophysics Data System (ADS)

Lao, L.; Grierson, B.; Burrell, K. H.

2016-10-01

Equilibrium analysis of plasmas in DIII-D using EFIT was upgraded to include the internal magnetic field determined from spectroscopic measurements of motional-Stark-effect line-splitting (MSE-LS). MSE-LS provides measurements of the magnitude of the internal magnetic field, rather than the pitch angle as provided by MSE line-polarization (MSE-LP) used in most tokamaks to date. EFIT MSE-LS reconstruction algorithms and verifications are described. The capability of MSE-LS to provide significant constraints on the equilibrium analysis is evaluated. Reconstruction results with both synthetic and experimental MSE-LS data from 10 DIII-D discharges run over a range of conditions show that MSE-LS measurements can contribute to the equilibrium reconstruction of pressure and safety factor profiles. Adequate MSE-LS measurement accuracy and number of spatial locations are necessary. The 7 available experimental measurements provide useful additional constraints when used with other internal measurements. Using MSE-LS as the only internal measurement yields less current profile information. Work supported by the PPPL Subcontract S013769-F and US DOE under DE-FC02-04ER54698.

Severe and acute complications of biologics in psoriasis.

PubMed

Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

2017-12-01

Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

To what extent can theory account for the findings of road safety evaluation studies?

PubMed

Elvik, Rune

2004-09-01

This paper proposes a conceptual framework that can be used to assess to what extent the findings of road safety evaluation research make sense from a theoretical point of view. The effects of road safety measures are modelled as passing through two causal chains. One of these, termed the engineering effect, refers to the intended effects of a road safety measure on a set of risk factors related to accident occurrence or injury severity. The engineering effect of road safety measures is modelled in terms of nine basic risk factors, one or more of which any road safety measure needs to influence in order to have the intended effect on accidents or injuries. The other causal chain producing the effects of road safety measures is termed the behavioural effect, and refers to road user behavioural adaptations to road safety measures. The behavioural effect is related to the engineering effect, in the sense that certain properties of the engineering effect of a road safety measure influence the likelihood that behavioural adaptation will occur. The behavioural effect of a road safety measure is modelled in terms of six factors that influence the likelihood that behavioural adaptation will occur. The nine basic risk factors representing the engineering effect of a road safety measure, and the six factors influencing the likelihood of behavioural adaptation can be used as checklists in assessing whether or not the findings of road safety evaluation studies make sense from a theoretical point of view. At the current state of knowledge, a more stringent evaluation of the extent to which theory can explain the findings of road safety evaluation studies is, in most cases, not possible. Copyright 2003 Elsevier Ltd.

Arterial hypertension in the female world: pathophysiology and therapy.

PubMed

Cadeddu, Christian; Franconi, Flavia; Cassisa, Laura; Campesi, Ilaria; Pepe, Alessia; Cugusi, Lucia; Maffei, Silvia; Gallina, Sabina; Sciomer, Susanna; Mercuro, Giuseppe

2016-04-01

Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown.

Psychometrics of the AAN Caregiver Driving Safety Questionnaire and contributors to caregiver concern about driving safety in older adults.

PubMed

Carvalho, Janessa O; Springate, Beth; Bernier, Rachel A; Davis, Jennifer

2018-03-01

ABSTRACTBackground:The American Academy of Neurology (AAN) updated their practice parameters in the evaluation of driving risk in dementia and developed a Caregiver Driving Safety Questionnaire, detailed in their original manuscript (Iverson Gronseth, Reger, Classen, Dubinsky, & Rizzo, 2010). They described four factors associated with decreased driving ability in dementia patients: history of crashes or citations, informant-reported concerns, reduced mileage, and aggressive driving. An informant-reported AAN Caregiver Driving Safety Questionnaire was designed with these elements, and the current study was the first to explore the factor structure of this questionnaire. Additionally, we examined associations between these factors and cognitive and behavioral measures in patients with mild cognitive impairment or early Alzheimer's disease and their informants. Exploratory factor analysis revealed a four-component structure, consistent with the theory behind the AAN scale composition. These four factor scores also were significantly associated with performance on cognitive screening instruments and informant reported behavioral dysfunction. Regressions revealed that behavioral dysfunction predicted caregiver concerns about driving safety beyond objective patient cognitive dysfunction. In this first known quantitative exploration of the scale, our results support continued use of this scale in office driving safety assessments. Additionally, patient behavioral changes predicted caregiver concerns about driving safety over and above cognitive status, which suggests that caregivers may benefit from psychoeducation about cognitive factors that may negatively impact driving safety.

Doppler Radar Profiler for Launch Winds at the Kennedy Space Center (Phase 1a)

NASA Technical Reports Server (NTRS)

Murri, Daniel G.

2011-01-01

The NASA Engineering and Safety Center (NESC) received a request from the, NASA Technical Fellow for Flight Mechanics at Langley Research Center (LaRC), to develop a database from multiple Doppler radar wind profiler (DRWP) sources and develop data processing algorithms to construct high temporal resolution DRWP wind profiles for day-of-launch (DOL) vehicle assessment. This document contains the outcome of Phase 1a of the assessment including Findings, Observations, NESC Recommendations, and Lessons Learned.

Patient safety culture in out-of-hours primary care services in the Netherlands: a cross-sectional survey.

PubMed

Smits, Marleen; Keizer, Ellen; Giesen, Paul; Deilkås, Ellen Catharina Tveter; Hofoss, Dag; Bondevik, Gunnar Tschudi

2018-03-01

To examine patient safety culture in Dutch out-of-hours primary care using the safety attitudes questionnaire (SAQ) which includes five factors: teamwork climate, safety climate, job satisfaction, perceptions of management and communication openness. Cross-sectional observational study using an anonymous web-survey. Setting Sixteen out-of-hours general practitioner (GP) cooperatives and two call centers in the Netherlands. Subjects Primary healthcare providers in out-of-hours services. Main outcome measures Mean scores on patient safety culture factors; association between patient safety culture and profession, gender, age, and working experience. Overall response rate was 43%. A total of 784 respondents were included; mainly GPs (N = 470) and triage nurses (N = 189). The healthcare providers were most positive about teamwork climate and job satisfaction, and less about communication openness and safety climate. The largest variation between clinics was found on safety climate; the lowest on teamwork climate. Triage nurses scored significantly higher than GPs on each of the five patient safety factors. Older healthcare providers scored significantly higher than younger on safety climate and perceptions of management. More working experience was positively related to higher teamwork climate and communication openness. Gender was not associated with any of the patient safety factors. Our study showed that healthcare providers perceive patient safety culture in Dutch GP cooperatives positively, but there are differences related to the respondents' profession, age and working experience. Recommendations for future studies are to examine reasons for these differences, to examine the effects of interventions to improve safety culture and to make international comparisons of safety culture. Key Points Creating a positive patient safety culture is assumed to be a prerequisite for quality and safety. We found that: • healthcare providers in Dutch GP cooperatives perceive patient safety culture positively; • triage nurses scored higher than GPs, and older and more experienced healthcare professionals scored higher than younger and less experienced professionals - on several patient safety culture factors; and • within the GP cooperatives, safety climate and openness of communication had the largest potential for improvement.

Patient safety culture in out-of-hours primary care services in the Netherlands: a cross-sectional survey

PubMed Central

Smits, Marleen; Keizer, Ellen; Giesen, Paul; Deilkås, Ellen Catharina Tveter; Hofoss, Dag; Bondevik, Gunnar Tschudi

2018-01-01

Objective To examine patient safety culture in Dutch out-of-hours primary care using the safety attitudes questionnaire (SAQ) which includes five factors: teamwork climate, safety climate, job satisfaction, perceptions of management and communication openness. Design Cross-sectional observational study using an anonymous web-survey. Setting Sixteen out-of-hours general practitioner (GP) cooperatives and two call centers in the Netherlands. Subjects Primary healthcare providers in out-of-hours services. Main outcome measures Mean scores on patient safety culture factors; association between patient safety culture and profession, gender, age, and working experience. Results Overall response rate was 43%. A total of 784 respondents were included; mainly GPs (N = 470) and triage nurses (N = 189). The healthcare providers were most positive about teamwork climate and job satisfaction, and less about communication openness and safety climate. The largest variation between clinics was found on safety climate; the lowest on teamwork climate. Triage nurses scored significantly higher than GPs on each of the five patient safety factors. Older healthcare providers scored significantly higher than younger on safety climate and perceptions of management. More working experience was positively related to higher teamwork climate and communication openness. Gender was not associated with any of the patient safety factors. Conclusions Our study showed that healthcare providers perceive patient safety culture in Dutch GP cooperatives positively, but there are differences related to the respondents’ profession, age and working experience. Recommendations for future studies are to examine reasons for these differences, to examine the effects of interventions to improve safety culture and to make international comparisons of safety culture. Key Points Creating a positive patient safety culture is assumed to be a prerequisite for quality and safety. We found that: • healthcare providers in Dutch GP cooperatives perceive patient safety culture positively; • triage nurses scored higher than GPs, and older and more experienced healthcare professionals scored higher than younger and less experienced professionals – on several patient safety culture factors; and • within the GP cooperatives, safety climate and openness of communication had the largest potential for improvement. PMID:29334826

Treatment of hemophilia B: focus on recombinant factor IX

PubMed Central

Franchini, Massimo; Frattini, Francesco; Crestani, Silvia; Sissa, Cinzia; Bonfanti, Carlo

2013-01-01

Hemophilia B is a recessive X-linked bleeding disorder characterized by deficiency of the coagulation factor IX (FIX). In hemophilia B patients the severity of the bleeding phenotype is related to the degree of the FIX defect. Hemophilia B treatment has improved greatly in the last 20 years with the introduction first of plasma-derived and then of recombinant FIX concentrates. Replacement therapy may be administered through on-demand or prophylaxis regimens, but the latter treatment modality has been shown to be superior in prevention of hemophilic arthropathy and in improvement of patients’ quality of life. The purpose of this narrative review is to summarize the current knowledge on treatment strategies for hemophilia B, focusing on recombinant FIX products either clinically used or in development. There is only one rFIX product that is licensed to treat hemophilia B patients; from the analysis of the literature data presented in this review, the authors conclude that this rFIX product has demonstrated an excellent safety profile and excellent clinical efficacy for halting and preventing bleeds in hemophilia B patients. While prophylaxis has emerged as the best therapeutic strategy for such patients because of its ability to prevent hemophilic arthropathy and to improve patients’ quality of life, the pharmacokinetically tailored dosing of rFIX is another key point when planning hemophilia B treatment, as it allows optimization of the factor concentrate usage. Further clinical studies are needed to better assess the safety and efficacy (ie, the incidence of adverse reactions and inhibitor development) of newer rFIX products. PMID:23430394

Stability of DIII-D high-performance, negative central shear discharges

DOE PAGES

Hanson, Jeremy M.; Berkery, John W.; Bialek, James M.; ...

2017-03-20

Tokamak plasma experiments on the DIII-D device demonstrate high-performance, negative central shear (NCS) equilibria with enhanced stability when the minimum safety factor q min exceeds 2, qualitatively confirming theoretical predictions of favorable stability in the NCS regime. The discharges exhibit good confinement with an L-mode enhancement factor H 89 = 2.5, and are ultimately limited by the ideal-wall external kink stability boundary as predicted by ideal MHD theory, as long as tearing mode (TM) locking events, resistive wall modes (RWMs), and internal kink modes are properly avoided or controlled. Although the discharges exhibit rotating TMs, locking events are avoided asmore » long as a threshold minimum safety factor value q min > 2 is maintained. Fast timescale magnetic feedback control ameliorates RWM activity, expanding the stable operating space and allowing access to β N values approaching the ideal-wall limit. Quickly growing and rotating instabilities consistent with internal kink mode dynamics are encountered when the ideal-wall limit is reached. The RWM events largely occur between the no- and ideal-wall pressure limits predicted by ideal MHD. However, evaluating kinetic contributions to the RWM dispersion relation results in a prediction of passive stability in this regime due to high plasma rotation. In addition, the ideal MHD stability analysis predicts that the ideal-wall limit can be further increased to β N > 4 by broadening the current profile. Furthermore, this path toward improved stability has the potential advantage of being compatible with the bootstrap-dominated equilibria envisioned for advanced tokamak (AT) fusion reactors.« less

The prevalence of fatigue and associated health and safety risk factors among taxi drivers in Singapore

PubMed Central

Lim, See Ming; Chia, Sin Eng

2015-01-01

INTRODUCTION Driver fatigue is one of the biggest health and safety concerns within the road transport sector. This study aimed to determine the prevalence of fatigue among taxi drivers in Singapore, to better understand the general working and health conditions of this group of people, and to determine the risk factors associated with fatigued driving. METHODS A total of 340 taxi drivers were randomly selected for participation in a self-administered questionnaire survey, which included height and weight measurements. The response rate was 68.2%. The survey consisted of four main categories: personal particulars; social habits; work patterns; and sleep profile. The Epworth Sleepiness Scale was used to estimate the level of daytime sleepiness and fatigue. Multiple logistic regression analysis was used to estimate the adjusted odd ratios and 95% confidence intervals associated with risk factors related to fatigue among taxi drivers. RESULTS A high proportion of taxi drivers were obese and had self-reported hypertension, diabetes mellitus and high cholesterol. Driver fatigue was associated with very poor/poor self-rating of quality of sleep, having an additional part-time job, drinking three or more caffeinated drinks daily, and driving more than 10 hours a day. CONCLUSION We hope that the findings of the present study will improve awareness of the work and health conditions of taxi drivers, and contribute toward efforts to achieve a healthier workforce. A lower prevalence of fatigued driving may lead to lower risks of road traffic accidents, decreased economic loss, increased productivity, and safer roads for all. PMID:25532512

The prevalence of fatigue and associated health and safety risk factors among taxi drivers in Singapore.

PubMed

Lim, See Ming; Chia, Sin Eng

2015-02-01

Driver fatigue is one of the biggest health and safety concerns within the road transport sector. This study aimed to find out the prevalence of fatigue among taxi drivers in Singapore, to better understand the general working and health conditions of this group of people and to determine the risk factors associated with fatigued driving. A total of 340 taxi drivers were randomly selected for participation in this self-administered questionnaire survey, with height and weight measurements. The response rate was 68.2%. The survey consisted of four main categories: personal particulars; social habits; work patterns and sleep profile; and Epworth Sleepiness Scale, which was used to estimate the level of daytime sleepiness and fatigue. Multiple logistic regression analysis was used to estimate the adjusted odd ratios and 95% confidence intervals associated with the risk factors related to fatigue among the taxi drivers. A high proportion of the taxi drivers were obese and had self-reported hypertension, diabetes mellitus and high cholesterol. Driver fatigue was associated with very poor/poor self-rating of the quality of sleep, having an additional part-time job, drinking three or more caffeinated drinks daily, and driving more than 10 hours a day. We hope that the findings of the present study will improve the awareness regarding the work and health conditions of taxi drivers, and contribute toward the effort to achieve a healthier workforce. A lower prevalence of fatigued driving will lead to lower risks of road traffic accidents, decreased economic loss, increased productivity, and safer roads for all.

Stability of DIII-D high-performance, negative central shear discharges

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

Hanson, Jeremy M.; Berkery, John W.; Bialek, James M.

Tokamak plasma experiments on the DIII-D device demonstrate high-performance, negative central shear (NCS) equilibria with enhanced stability when the minimum safety factor q min exceeds 2, qualitatively confirming theoretical predictions of favorable stability in the NCS regime. The discharges exhibit good confinement with an L-mode enhancement factor H 89 = 2.5, and are ultimately limited by the ideal-wall external kink stability boundary as predicted by ideal MHD theory, as long as tearing mode (TM) locking events, resistive wall modes (RWMs), and internal kink modes are properly avoided or controlled. Although the discharges exhibit rotating TMs, locking events are avoided asmore » long as a threshold minimum safety factor value q min > 2 is maintained. Fast timescale magnetic feedback control ameliorates RWM activity, expanding the stable operating space and allowing access to β N values approaching the ideal-wall limit. Quickly growing and rotating instabilities consistent with internal kink mode dynamics are encountered when the ideal-wall limit is reached. The RWM events largely occur between the no- and ideal-wall pressure limits predicted by ideal MHD. However, evaluating kinetic contributions to the RWM dispersion relation results in a prediction of passive stability in this regime due to high plasma rotation. In addition, the ideal MHD stability analysis predicts that the ideal-wall limit can be further increased to β N > 4 by broadening the current profile. Furthermore, this path toward improved stability has the potential advantage of being compatible with the bootstrap-dominated equilibria envisioned for advanced tokamak (AT) fusion reactors.« less

Effect of Aripiprazole Lauroxil on Metabolic and Endocrine Profiles and Related Safety Considerations Among Patients With Acute Schizophrenia.

PubMed

Nasrallah, Henry A; Newcomer, John W; Risinger, Robert; Du, Yangchun; Zummo, Jacqueline; Bose, Anjana; Stankovic, Srdjan; Silverman, Bernard L; Ehrich, Elliot W

2016-11-01

Aripiprazole lauroxil, a long-acting injectable antipsychotic, demonstrated safety and efficacy in treating symptoms of schizophrenia in a double-blind, placebo-controlled trial. Because the metabolic profile of antipsychotics is an important safety feature, the effects of aripiprazole lauroxil on body weight, endocrine and metabolic profiles, and safety were examined in a secondary analysis. Patients with schizophrenia (DSM-IV-TR criteria) were randomly assigned to aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, or placebo intramuscularly once monthly between December 2011 and March 2014. Changes in body weight, body mass index, fasting blood glucose and serum lipids, glycosylated hemoglobin (HbA1c), and prolactin over 12 weeks were assessed. The incidence of treatment-emergent adverse events (AEs) was evaluated. Among 622 randomized patients, no clinically relevant changes from baseline to week 12 were observed for any serum lipid, lipoprotein, plasma glucose, or HbA1c value with placebo or either dose of aripiprazole lauroxil. Both doses of aripiprazole lauroxil were associated with reductions in mean prolactin levels, whereas placebo treatment was not. The mean (standard deviation) change from baseline for body weight was 0.74 (3.9) kg, 0.86 (3.7) kg, and 0.01 (3.6) kg for aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. AEs related to metabolic parameters were reported in 2.4%, 1.4%, and 2.4% of patients in the aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. Aripiprazole lauroxil was well tolerated, with a low-risk metabolic profile relative to published data for other antipsychotics. Changes similar to those observed with placebo were observed in the aripiprazole lauroxil groups for metabolic parameters, with modest weight gain in the active treatment groups over the 12-week course. ClinicalTrials.gov identifier: NCT01469039. © Copyright 2016 Physicians Postgraduate Press, Inc.

Space station crew safety alternatives study. Volume 3: Safety impact of human factors

NASA Technical Reports Server (NTRS)

Rockoff, L. A.; Raasch, R. F.; Peercy, R. L., Jr.

1985-01-01

The first 15 years of accumulated space station concepts for Initial Operational Capability (IOC) during the early 1990's was considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris. Of particular interest here is volume three (of five volumes) pertaining to the safety impact of human factors.

The Use of Twitter by Radiology Journals: An Analysis of Twitter Activity and Impact Factor.

PubMed

Kelly, Brendan S; Redmond, Ciaran E; Nason, Gregory J; Healy, Gerard M; Horgan, Niall A; Heffernan, Eric J

2016-11-01

Medical journals use social media as a means to disseminate new research and interact with readers. The microblogging site Twitter is one such platform. The aim of this study was to analyze the recent use of Twitter by the leading radiology journals. The top 50 journals by Impact Factor were included. Twitter profiles associated with these journals, or their corresponding societies, were identified. Whether each journal used other social media platforms was also recorded. Each Twitter profile was analyzed over a one-year period, with data collected via Twitonomy software. Klout scores of social media influence were calculated. Results were analyzed in SPSS using Student's t test, Fisher contingency tables, and Pearson correlations to identify any association between social media interaction and Impact Factors of journals. Fourteen journals (28%) had dedicated Twitter profiles. Of the 36 journals without dedicated Twitter profiles, 25 (50%) were associated with societies that had profiles, leaving 11 (22%) journals without a presence on Twitter. The mean Impact Factor of all journals was 3.1 ± 1.41 (range, 1.7-6.9). Journals with Twitter profiles had higher Impact Factors than those without (mean, 3.37 vs 2.14; P < .001). There was no statistically significant difference between the Impact Factors of the journals with dedicated Twitter profiles and those associated with affiliated societies (P = .47). Since joining Twitter, 7 of the 11 journals (64%) experienced increases in Impact Factor. A greater number of Twitter followers was correlated with higher journal Impact Factor (R 2  = 0.581, P = .029). The investigators assessed the prevalence and activity of the leading radiology journals on Twitter. Radiology journals with Twitter profiles have higher Impact Factors than those without profiles, and the number of followers of a journal's Twitter profile is positively associated with Impact Factor. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Critical safety assurance factors for manned spacecraft - A fire safety perspective

NASA Technical Reports Server (NTRS)

Rodney, George A.

1990-01-01

Safety assurance factors for manned spacecraft are discussed with a focus on the Space Station Freedom. A hazard scenario is provided to demonstrate a process commonly used by safety engineers and other analysts to identify onboard safety risks. Fire strategies are described, including a review of fire extinguishing agents being considered for the Space Station. Lessons learned about fire safety technology in other areas are also noted. NASA and industry research on fire safety applications is discussed. NASA's approach to ensuring safety for manned spacecraft is addressed in the context of its multidiscipline program.

Factors related to increasing safety belt use in states with safety belt use laws : second annual report to Congress

DOT National Transportation Integrated Search

1989-01-01

This report is the second in a series of four annual reports to the Congress on provisions of state safety belt use laws and other programmatic factors related to increasing safety belt use levels. The first Congressional Report reviewed what was kno...

Factors related to increasing safety belt use in states with safety belt use laws : second annual report to Congress, 1988.

DOT National Transportation Integrated Search

1989-01-01

This report. is the second in a series of four annual reports to the : Congress on provisions of state safety belt use laws and other : programmatic factors related to increasing safety belt use levels. : The first Congressional Report reviewed what ...

Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines.

PubMed

Pane, Josep; Coloma, Preciosa M; Verhamme, Katia M C; Sturkenboom, Miriam C J M; Rebollo, Irene

2017-01-01

Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit-risk monitoring of these devices throughout their entire life cycle. A literature review served to examine the current tools for the safety evaluation of NAIMDs and those for medicines. We searched MEDLINE using these two categories. We supplemented this search with Google searches using the same key terms used in the MEDLINE search. Using a comparative approach, we summarized the new product design, development cycle (preclinical and clinical phases), and post-market phases for NAIMDs and drugs. We also evaluated and compared the respective processes to integrate and assess safety data during the life cycle of the products, including signal detection, signal management, and subsequent potential regulatory actions. The search identified a gap in NAIMD safety signal generation: no global program exists that collects and analyzes adverse events and product quality issues. Data sources in real-world settings, such as electronic health records, need to be effectively identified and explored as additional sources of safety information, particularly in some areas such as the EU and USA where there are plans to implement the unique device identifier (UDI). The UDI and other initiatives will enable more robust follow-up and assessment of long-term patient outcomes. The safety evaluation system for NAIMDs differs in many ways from those for drugs, but both systems face analogous challenges with respect to monitoring real-world usage. Certain features of the drug safety evaluation process could, if adopted and adapted for NAIMDs, lead to better and more systematic evaluations of the latter.

Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status.

PubMed

Allam-Ndoul, Bénédicte; Guénard, Frédéric; Garneau, Véronique; Cormier, Hubert; Barbier, Olivier; Pérusse, Louis; Vohl, Marie-Claude

2016-05-27

Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1's (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3's (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

PubMed

Scott, Lesley J

2018-05-01

Apatinib [Aitan ® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

PubMed Central

Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

2014-01-01

Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

The Safety Attitudes Questionnaire: psychometric properties, benchmarking data, and emerging research.

PubMed

Sexton, John B; Helmreich, Robert L; Neilands, Torsten B; Rowan, Kathy; Vella, Keryn; Boyden, James; Roberts, Peter R; Thomas, Eric J

2006-04-03

There is widespread interest in measuring healthcare provider attitudes about issues relevant to patient safety (often called safety climate or safety culture). Here we report the psychometric properties, establish benchmarking data, and discuss emerging areas of research with the University of Texas Safety Attitudes Questionnaire. Six cross-sectional surveys of health care providers (n = 10,843) in 203 clinical areas (including critical care units, operating rooms, inpatient settings, and ambulatory clinics) in three countries (USA, UK, New Zealand). Multilevel factor analyses yielded results at the clinical area level and the respondent nested within clinical area level. We report scale reliability, floor/ceiling effects, item factor loadings, inter-factor correlations, and percentage of respondents who agree with each item and scale. A six factor model of provider attitudes fit to the data at both the clinical area and respondent nested within clinical area levels. The factors were: Teamwork Climate, Safety Climate, Perceptions of Management, Job Satisfaction, Working Conditions, and Stress Recognition. Scale reliability was 0.9. Provider attitudes varied greatly both within and among organizations. Results are presented to allow benchmarking among organizations and emerging research is discussed. The Safety Attitudes Questionnaire demonstrated good psychometric properties. Healthcare organizations can use the survey to measure caregiver attitudes about six patient safety-related domains, to compare themselves with other organizations, to prompt interventions to improve safety attitudes and to measure the effectiveness of these interventions.

The role of psychological factors in workplace safety.

PubMed

Kotzé, Martina; Steyn, Leon

2013-01-01

Workplace safety researchers and practitioners generally agree that it is necessary to understand the psychological factors that influence people's workplace safety behaviour. Yet, the search for reliable individual differences regarding psychological factors associated with workplace safety has lead to sparse results and inconclusive findings. The aim of this study was to investigate whether there are differences between the psychological factors, cognitive ability, personality and work-wellness of employees involved in workplace incidents and accidents and/or driver vehicle accidents and those who are not. The study population (N = 279) consisted of employees employed at an electricity supply organisation in South Africa. Mann-Whitney U-test and one-way ANOVA were conducted to determine the differences in the respective psychological factors between the groups. These results showed that cognitive ability did not seem to play a role in workplace incident/accident involvement, including driver vehicle accidents, while the wellness factors burnout and sense of coherence, as well as certain personality traits, namely conscientiousness, pragmatic and gregariousness play a statistically significant role in individuals' involvement in workplace incidents/accidents/driver vehicle accidents. Safety practitioners, managers and human resource specialists should take cognisance of the role of specifically work-wellness in workplace safety behaviour, as management can influence these negative states that are often caused by continuously stressful situations, and subsequently enhance work place safety.

Phase I/II evaluation of RV1001, a novel PI3Kδ inhibitor, in spontaneous canine lymphoma.

PubMed

Gardner, Heather L; Rippy, Sarah B; Bear, Misty D; Cronin, Kim L; Heeb, Heather; Burr, Holly; Cannon, Claire M; Penmetsa, Kumar V; Viswanadha, Srikant; Vakkalanka, Swaroop; London, Cheryl A

2018-01-01

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL). Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity. RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.

ELECTRO CONVULSIVE THERAPY IN PRE-PUBERTAL CATATONIA: A CASE STUDY

PubMed Central

Thakur, Anupam; Dutta, S.; Jagadheesan, K.; Sinha, Vinod Kumar

2001-01-01

Depression in prepubertal age group is a relatively rare condition. The presence of life threatening catatonic features call for aggressive treatment. Electro convulsive therapy (ECT) has been described to be effective in these circumstances; however, doubts have been raised about its safety profile. This present case study illustrates the efficacy and safety of ECT in prepubertal catatonia. PMID:21407888

Heparin pharmacovigilance in Brazil.

PubMed

Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R de M; Barros, Fabiana C R de; Carvalho, Maria das Graças; Perini, Edson

2011-01-01

To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

Advanced Range Safety System for High Energy Vehicles

NASA Technical Reports Server (NTRS)

Claxton, Jeffrey S.; Linton, Donald F.

2002-01-01

The advanced range safety system project is a collaboration between the National Aeronautics and Space Administration and the United States Air Force to develop systems that would reduce costs and schedule for safety approval for new classes of unmanned high-energy vehicles. The mission-planning feature for this system would yield flight profiles that satisfy the mission requirements for the user while providing an increased quality of risk assessment, enhancing public safety. By improving the speed and accuracy of predicting risks to the public, mission planners would be able to expand flight envelopes significantly. Once in place, this system is expected to offer the flexibility of handling real-time risk management for the high-energy capabilities of hypersonic vehicles including autonomous return-from-orbit vehicles and extended flight profiles over land. Users of this system would include mission planners of Space Launch Initiative vehicles, space planes, and other high-energy vehicles. The real-time features of the system could make extended flight of a malfunctioning vehicle possible, in lieu of an immediate terminate decision. With this improved capability, the user would have more time for anomaly resolution and potential recovery of a malfunctioning vehicle.

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

An open-label pilot study to assess the efficacy and safety of virgin coconut oil in reducing visceral adiposity.

PubMed

Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G

2011-01-01

Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans.

Cardiovascular safety of prokinetic agents: A focus on drug-induced arrhythmias.

PubMed

Giudicessi, J R; Ackerman, M J; Camilleri, M

2018-02-14

Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use. The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully. © 2018 John Wiley & Sons Ltd.

Balancing efficacy against safety in sublingual immunotherapy with inhalant allergens: what is the best approach?

PubMed

Caminati, Marco; Dama, Annarita; Schiappoli, Michele; Senna, Gianenrico

2013-10-01

Over the last 20 years, studies and clinical trials have demonstrated efficacy, safety and cost-effectiveness of sublingual immunotherapy (SLIT) for respiratory allergic diseases. Nevertheless, it seems to be mostly used as a second-line therapeutic option, and adherence to treatment is not always optimal. Selective literature research was done in Medline and PubMed, including guidelines, position papers and Cochrane meta-analyses concerning SLIT in adult patients. The most recent reviews confirm SLIT as viable and efficacious treatment especially for allergic rhinitis, even if the optimal dosage, duration, schedule are not clearly established for most of the products. Despite an optimal safety profile, tolerability and patient-reported outcomes concerning SLIT have received poor attention until now. Recently, new tools have been specifically developed in order to investigate these aspects. Regular assessment of tolerability profile and SLIT-related patient-reported outcomes will allow balancing efficacy with tolerability and all the other patient-related variables that may affect treatment effectiveness beyond its efficacy.

Safety of treatment options for spondyloarthritis: a narrative review.

PubMed

D'Angelo, Salvatore; Carriero, Antonio; Gilio, Michele; Ursini, Francesco; Leccese, Pietro; Palazzi, Carlo

2018-05-01

Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations. Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.

Safety and efficacy of elbasvir and grazoprevir for treatment of hepatitis C.

PubMed

Carrion, Andres F; Martin, Paul

2016-06-01

The combination of elbasvir and grazoprevir in a single co-formulated tablet is highly effective for treatment of hepatitis C virus (HCV) infection. This regimen affords profound inhibition of NS3/4A protease and NS5A activity, resulting in potent activity against HCV genotypes 1, 4, and 6 with high rates of sustained virological response. This review covers the mechanism of action, pharmacokinetics, clinical applications, efficacy and safety profile of elbasvir/grazoprevir including special populations such as individuals with compensated and decompensated cirrhosis, HCV/HIV co-infection, advanced chronic kidney disease, and those that previously failed antiviral therapy. Elbasvir/grazoprevir is an effective antiviral regimen for treatment of genotypes 1 and 4 and has a very favorable safety profile based on extensive data from several pre-licensure clinical trials that included patient subgroups at increased risk of toxicity. This regimen is currently the only one licensed for use in individuals with advanced chronic kidney disease requiring hemodialysis.

An Open-Label Pilot Study to Assess the Efficacy and Safety of Virgin Coconut Oil in Reducing Visceral Adiposity

PubMed Central

Liau, Kai Ming; Lee, Yeong Yeh; Chen, Chee Keong; Rasool, Aida Hanum G.

2011-01-01

Introduction. This is an open-label pilot study on four weeks of virgin coconut oil (VCO) to investigate its efficacy in weight reduction and its safety of use in 20 obese but healthy Malay volunteers. Methodology. Efficacy was assessed by measuring weight and associated anthropometric parameters and lipid profile one week before and one week after VCO intake. Safety was assessed by comparing organ function tests one week before and one week after intake of VCO. Paired t-test was used to analyse any differences in all the measurable variables. Results. Only waist circumference (WC) was significantly reduced with a mean reduction of 2.86 cm or 0.97% from initial measurement (P = .02). WC reduction was only seen in males (P < .05). There was no change in the lipid profile. There was a small reduction in creatinine and alanine transferase levels. Conclusion. VCO is efficacious for WC reduction especially in males and it is safe for use in humans. PMID:22164340

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

PubMed Central

Zhang, Wenli; Muck-Hausl, Martin; Wang, Jichang; Sun, Chuanbo; Gebbing, Maren; Miskey, Csaba; Ivics, Zoltan; Izsvak, Zsuzsanna; Ehrhardt, Anja

2013-01-01

We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models. PMID:24124483

Profiles of bullying victimization, discrimination, social support, and school safety: Links with Latino/a youth acculturation, gender, depressive symptoms, and cigarette use.

PubMed

Lorenzo-Blanco, Elma I; Unger, Jennifer B; Oshri, Assaf; Baezconde-Garbanati, Lourdes; Soto, Daniel

2016-01-01

Latino/a youth are at risk for symptoms of depression and cigarette smoking but this risk varies by acculturation and gender. To understand why some youth are at greater risk than others, we identified profiles of diverse community experiences (perceived discrimination, bullying victimization, social support, perceived school safety) and examined associations between profiles of community experience and depressive symptoms, cigarette smoking, acculturation, and gender. Data came from Project Red (Reteniendo y Entendiendo Diversidad para Salud), a school-based longitudinal study of acculturation among 1,919 Latino/a adolescents (52% female; 84% 14 years old; 87% U.S. born). Latent profile analysis (LPA) revealed 4 distinct profiles of community experience that varied by gender and acculturation. Boys were overrepresented in profile groups with high perceived discrimination, some bullying, and lack of positive experiences, while girls were overrepresented in groups with high bullying victimization in the absence and presence of other community experiences. Youth low on both U.S. and Latino/a cultural orientation described high perceived discrimination and lacked positive experiences, and were predominantly male. Profiles characterized by high perceived discrimination and /or high bullying victimization in the absence of positive experiences had higher levels of depressive symptoms and higher risk of smoking, relative to the other groups. Findings suggest that acculturation comes with diverse community experiences that vary by gender and relate to smoking and depression risk. Results from this research can inform the development of tailored intervention and prevention strategies to reduce depression and/or smoking for Latino/a youth. (c) 2016 APA, all rights reserved).

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency.

PubMed

Kulkarni, R; James, A H; Norton, M; Shapiro, A

2018-05-01

Essentials Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU kg -1 was effective and safe in women/girls with factor X deficiency. Background A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL -1 ) received on-demand or preventive pdFX (25 IU kg -1 ) for ≤ 2 years. Results Of 16 enrolled subjects, 10 women and girls (aged 14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pdFX, with a 98% treatment success rate versus 100% in men and boys. Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL -1 versus 1.91 IU dL -1 per IU kg -1 ), as was the mean half-life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion-site erythema, two fatigue, one back pain, one infusion-site pain) in two subjects were considered to be possibly pdFX-related. Following the trial, pdFX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions pdFX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pdFX pharmacokinetic profile was comparable. © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Core transport properties in JT-60U and JET identity plasmas

NASA Astrophysics Data System (ADS)

Litaudon, X.; Sakamoto, Y.; de Vries, P. C.; Salmi, A.; Tala, T.; Angioni, C.; Benkadda, S.; Beurskens, M. N. A.; Bourdelle, C.; Brix, M.; Crombé, K.; Fujita, T.; Futatani, S.; Garbet, X.; Giroud, C.; Hawkes, N. C.; Hayashi, N.; Hoang, G. T.; Hogeweij, G. M. D.; Matsunaga, G.; Nakano, T.; Oyama, N.; Parail, V.; Shinohara, K.; Suzuki, T.; Takechi, M.; Takenaga, H.; Takizuka, T.; Urano, H.; Voitsekhovitch, I.; Yoshida, M.; ITPA Transport Group; JT-60 Team; EFDA contributors, JET

2011-07-01

The paper compares the transport properties of a set of dimensionless identity experiments performed between JET and JT-60U in the advanced tokamak regime with internal transport barrier, ITB. These International Tokamak Physics Activity, ITPA, joint experiments were carried out with the same plasma shape, toroidal magnetic field ripple and dimensionless profiles as close as possible during the ITB triggering phase in terms of safety factor, normalized Larmor radius, normalized collision frequency, thermal beta, ratio of ion to electron temperatures. Similarities in the ITB triggering mechanisms and sustainment were observed when a good match was achieved of the most relevant normalized profiles except the toroidal Mach number. Similar thermal ion transport levels in the two devices have been measured in either monotonic or non-monotonic q-profiles. In contrast, differences between JET and JT-60U were observed on the electron thermal and particle confinement in reversed magnetic shear configurations. It was found that the larger shear reversal in the very centre (inside normalized radius of 0.2) of JT-60U plasmas allowed the sustainment of stronger electron density ITBs compared with JET. As a consequence of peaked density profile, the core bootstrap current density is more than five times higher in JT-60U compared with JET. Thanks to the bootstrap effect and the slightly broader neutral beam deposition, reversed magnetic shear configurations are self-sustained in JT-60U scenarios. Analyses of similarities and differences between the two devices address key questions on the validity of the usual assumptions made in ITER steady scenario modelling, e.g. a flat density profile in the core with thermal transport barrier? Such assumptions have consequences on the prediction of fusion performance, bootstrap current and on the sustainment of the scenario.

Shaping ability and safety of five different rotary nickel-titanium instruments compared with stainless steel hand instrumentation in simulated curved root canals.

PubMed

Schirrmeister, Jörg F; Strohl, Christian; Altenburger, Markus J; Wrbas, Karl-Thomas; Hellwig, Elmar

2006-06-01

To compare the shaping ability and safety of engine-driven FlexMaster, GT Rotary, ProFile, ProTaper, and RaCe rotary instrumentation and Hedström hand instrumentation in simulated root canals. One hundred fifty simulated colored root canals with a curvature of 20 degrees and a radius of 10 mm were randomly distributed among 6 groups of 25 specimens each. After preparation to apical size 30 the area of remaining color on the canal wall indicating unprepared areas was measured in mm2 using image analyzer software. Specimens treated with RaCe left least areas of remaining color compared to all other groups (P < .001), followed by ProTaper. Preparation with ProFile left behind the highest amount of unprepared areas. The ProFile group revealed significantly more remaining color than ProTaper, GT Rotary, and FlexMaster (P < .05). Four FlexMaster files separated. RaCe rotary files were safe and more effective compared to the other instruments.

Evaluating the Effectiveness of an Educational Intervention to Improve the Patient Safety Attitudes of Intern Pharmacists

PubMed Central

Fois, Romano A.; McLachlan, Andrew J.; Chen, Timothy F.

2017-01-01

Objective. To evaluate the effectiveness of a face-to-face educational intervention in improving the patient safety attitudes of intern pharmacists. Methods. A patient safety education program was delivered to intern pharmacists undertaking The University of Sydney Intern Training Program in 2014. Their patient safety attitudes were evaluated immediately prior to, immediately after, and three-months post-intervention. Underlying attitudinal factors were identified using exploratory factor analysis. Changes in factor scores were examined using analysis of variance. Results. Of the 120 interns enrolled, 95 (78.7%) completed all three surveys. Four underlying attitudinal factors were identified: attitudes towards addressing errors, questioning behaviors, blaming individuals, and reporting errors. Improvements in all attitudinal factors were evident immediately after the intervention. However, only improvements in attitudes towards blaming individuals involved in errors were sustained at three months post-intervention. Conclusion. The educational intervention was associated with short-term improvements in pharmacist interns’ patient safety attitudes. However, other factors likely influenced their attitudes in the longer term. PMID:28289295

Evaluating the Effectiveness of an Educational Intervention to Improve the Patient Safety Attitudes of Intern Pharmacists.

PubMed

Walpola, Ramesh L; Fois, Romano A; McLachlan, Andrew J; Chen, Timothy F

2017-02-25

Objective. To evaluate the effectiveness of a face-to-face educational intervention in improving the patient safety attitudes of intern pharmacists. Methods. A patient safety education program was delivered to intern pharmacists undertaking The University of Sydney Intern Training Program in 2014. Their patient safety attitudes were evaluated immediately prior to, immediately after, and three-months post-intervention. Underlying attitudinal factors were identified using exploratory factor analysis. Changes in factor scores were examined using analysis of variance. Results. Of the 120 interns enrolled, 95 (78.7%) completed all three surveys. Four underlying attitudinal factors were identified: attitudes towards addressing errors, questioning behaviors, blaming individuals, and reporting errors. Improvements in all attitudinal factors were evident immediately after the intervention. However, only improvements in attitudes towards blaming individuals involved in errors were sustained at three months post-intervention. Conclusion. The educational intervention was associated with short-term improvements in pharmacist interns' patient safety attitudes. However, other factors likely influenced their attitudes in the longer term.

Old and new adjuvants for hepatitis B vaccines.

PubMed

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

Cyclooxygenase-2 inhibitors: promise or peril?

PubMed Central

Mengle-Gaw, Laurel J; Schwartz, Benjamin D

2002-01-01

The discovery of two isoforms of the cyclooxygenase enzyme, COX-1 and COX-2, and the development of COX-2-specific inhibitors as anti-inflammatories and analgesics have offered great promise that the therapeutic benefits of NSAIDs could be optimized through inhibition of COX-2, while minimizing their adverse side effect profile associated with inhibition of COX-1. While COX-2 specific inhibitors have proven to be efficacious in a variety of inflammatory conditions, exposure of large numbers of patients to these drugs in postmarketing studies have uncovered potential safety concerns that raise questions about the benefit/risk ratio of COX-2-specific NSAIDs compared to conventional NSAIDs. This article reviews the efficacy and safety profiles of COX-2-specific inhibitors, comparing them with conventional NSDAIDs. PMID:12467519

Positive organizational behavior and safety in the offshore oil industry: Exploring the determinants of positive safety climate.

PubMed

Hystad, Sigurd W; Bartone, Paul T; Eid, Jarle

2014-01-01

Much research has now documented the substantial influence of safety climate on a range of important outcomes in safety critical organizations, but there has been scant attention to the question of what factors might be responsible for positive or negative safety climate. The present paper draws from positive organizational behavior theory to test workplace and individual factors that may affect safety climate. Specifically, we explore the potential influence of authentic leadership style and psychological capital on safety climate and risk outcomes. Across two samples of offshore oil-workers and seafarers working on oil platform supply ships, structural equation modeling yielded results that support a model in which authentic leadership exerts a direct effect on safety climate, as well as an indirect effect via psychological capital. This study shows the importance of leadership qualities as well as psychological factors in shaping a positive work safety climate and lowering the risk of accidents.

Positive organizational behavior and safety in the offshore oil industry: Exploring the determinants of positive safety climate

PubMed Central

Hystad, Sigurd W.; Bartone, Paul T.; Eid, Jarle

2013-01-01

Much research has now documented the substantial influence of safety climate on a range of important outcomes in safety critical organizations, but there has been scant attention to the question of what factors might be responsible for positive or negative safety climate. The present paper draws from positive organizational behavior theory to test workplace and individual factors that may affect safety climate. Specifically, we explore the potential influence of authentic leadership style and psychological capital on safety climate and risk outcomes. Across two samples of offshore oil-workers and seafarers working on oil platform supply ships, structural equation modeling yielded results that support a model in which authentic leadership exerts a direct effect on safety climate, as well as an indirect effect via psychological capital. This study shows the importance of leadership qualities as well as psychological factors in shaping a positive work safety climate and lowering the risk of accidents. PMID:24454524