Novel approaches to the pharmacotherapy of obesity.

PubMed

Gouni-Berthold, Ioanna; Brüning, Jens C; Berthold, Heiner K

2013-01-01

Although the obesity epidemic is constantly expanding at very high costs for health care systems, the currently available options for the pharmacotherapy of obesity are very limited. This is not due to lack of interest or research on the subject but rather to the poor efficacy and/or safety profile of the majority of the antiobesity drugs developed up to now. Since the late fifties, various medications were brought to advanced states of clinical development but either never made it to the market or were initially approved only to be withdrawn some years later because of safety issues. However, our understanding of the pathophysiology of obesity has been steadily increasing and new, promising drugs targeting various selected obesity-associated and energy-homeostasis-related pathways are now under development. Nonetheless, obesity remains a disease mainly caused by an excess of caloric intake in relation to energy expenditure and on that basis, its treatment should be a healthy diet and physical activity. When these options alone are not sufficient, then additional pharmacotherapy with an acceptable efficacy and safety profile could provide a useful option.

A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico.

PubMed

Bauer, Kristen; Esquilin, Ines O; Cornier, Alberto Santiago; Thomas, Stephen J; Quintero Del Rio, Ana I; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L

2015-09-01

This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1-50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2-4 years], 60% [5-20 years], and 93% [21-50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. © The American Society of Tropical Medicine and Hygiene.

Medication safety research by observational study design.

PubMed

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

2016-06-01

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

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

Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

PubMed

Garcia-Sicilia, José; Arístegui, Javier; Omeñaca, Félix; Carmona, Alfonso; Tejedor, Juan C; Merino, José M; García-Corbeira, Pilar; Walravens, Karl; Bambure, Vinod; Moris, Philippe; Caplanusi, Adrian; Gillard, Paul; Dieussaert, Ilse

2015-01-01

In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

Quantitative PCR and disaccharide profiling to characterize the animal origin of low-molecular-weight heparins.

PubMed

Houiste, Céline; Auguste, Cécile; Macrez, Céline; Dereux, Stéphanie; Derouet, Angélique; Anger, Pascal

2009-02-01

Low-molecular-weight heparins (LMWHs) are widely used in the management of thrombosis and acute coronary syndromes. They are obtained by the enzymatic or chemical depolymerization of porcine intestinal heparin. Enoxaparin sodium, a widely used LMWH, has a unique and reproducible oligosaccharide profile which is determined by the origin of the starting material and a tightly controlled manufacturing process. Although other enoxaparin-like LMWHs do exist, specific release criteria including the origin of the crude heparin utilized for their production, have not been established. A quantitative polymerase chain reaction method has been developed to ensure the purity of the porcine origin of crude heparin, with a DNA detection limit as low as 1 ppm for bovine, or 10 ppm for ovine contaminants. This method is routinely used as the release acceptance criterion during enoxaparin sodium manufacturing. Furthermore, when the process removes DNA, other analytical techniques can be used to assess any contamination. Disaccharide profiling after exhaustive depolymerization can determine the presence of at least 10% bovine or 20% ovine material; multivariate analysis is useful to perform the data analysis. Consistent with the availability of newer technology, these methods should be required as acceptance criteria for crude heparins used in the manufacture of LMWHs to ensure their safety, quality, and immunologic profile.

30 CFR 6.20 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false MSHA acceptance of equivalent non-MSHA product... LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.20 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non-MSHA product safety standards, or groups of standards, as equivalent...

30 CFR 6.20 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false MSHA acceptance of equivalent non-MSHA product... LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.20 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non-MSHA product safety standards, or groups of standards, as equivalent...

30 CFR 6.20 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false MSHA acceptance of equivalent non-MSHA product... LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.20 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non-MSHA product safety standards, or groups of standards, as equivalent...

30 CFR 6.20 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false MSHA acceptance of equivalent non-MSHA product... LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.20 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non-MSHA product safety standards, or groups of standards, as equivalent...

30 CFR 6.20 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false MSHA acceptance of equivalent non-MSHA product... LABORATORIES AND NON-MSHA PRODUCT SAFETY STANDARDS § 6.20 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non-MSHA product safety standards, or groups of standards, as equivalent...

Predictors of nurses' acceptance of an intravenous catheter safety device.

PubMed

Rivers, Dianna Lipp; Aday, Lu Ann; Frankowski, Ralph F; Felknor, Sarah; White, Donna; Nichols, Brenda

2003-01-01

It is important to determine the factors that predict whether nurses accept and use a new intravenous (IV) safety device because there are approximately 800,000 needlesticks per year with the risk of contracting a life-threatening bloodborne disease such as HIV or hepatitis C. To determine the predictors of nurses' acceptance of the Protectiv Plus IV catheter safety needle device at a teaching hospital in Texas. A one-time cross-sectional survey of nurses (N = 742) was conducted using a 34-item questionnaire. A framework was developed identifying organizational and individual predictors of acceptance. The three principal dimensions of acceptance were (a) satisfaction with the device, (b) extent to which the device is always used, and (c) nurse recommendations over other safety devices. Measurements included developing summary subscales for the variables of safety climate and acceptance. Descriptive statistics and multiple linear and logistic regression models were computed. The findings showed widespread acceptance of the device. Nurses who had adequate training and a positive institutional safety climate were more accepting (p

Long-term safety concerns with proton pump inhibitors.

PubMed

Ali, Tauseef; Roberts, David Neil; Tierney, William M

2009-10-01

Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide. Their use has resulted in dramatic improvements in treatment of peptic ulcer disease and gastroesophageal reflux disease. Despite an acceptable safety profile, mounting data demonstrate concerns about the long-term use of PPIs. To provide a comprehensive review regarding the concerns of long-term PPI use, a literature search was performed to identify pertinent original and review articles. Despite study shortcomings, the collective body of information overwhelmingly suggests an increased risk of infectious complications and nutritional deficiencies. Data regarding any increased risk in gastric or colon malignancy are less convincing. PPIs have revolutionized the management and complications of acid-related disorders with a high margin of safety; however, with the data available, efforts to reduce the dosing of or discontinue the use of PPIs must be reassessed frequently.

Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

PubMed Central

Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

2016-01-01

Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women. Trial Registration ClinicalTrials.gov NCT01071174 PMID:26963505

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.

The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine.

PubMed

Dbaibo, Ghassan; Van der Wielen, Marie; Reda, Mariam; Medlej, Fouad; Tabet, Carelle; Boutriau, Dominique; Sumbul, Anne; Anis, Sameh; Miller, Jacqueline M

2012-08-01

The immunogenicity and safety of the tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in subjects previously vaccinated with a tetravalent meningococcal polysaccharide vaccine and in subjects without previous meningococcal vaccination. In this phase II, open, controlled study (NCT00661557), healthy subjects aged 4.5-34 years received one dose of MenACWY-TT at month 0. Subjects in the MPS group (n=192) had received polysaccharide vaccine in a study conducted 30-42 months earlier; age-matched subjects in the noMPS control group (n=79) had received no meningococcal vaccination within the past 10 years. Serum bactericidal activity using rabbit complement (rSBA) was measured at month 0 and month 1. At month 1, ≥97.0% of subjects had rSBA titers ≥1:128. Post-vaccination rSBA geometric mean titers (GMTs) were ≥3.9-fold higher than pre-vaccination in both treatment groups. Exploratory analyses showed no statistically significant differences between groups in percentages of subjects with rSBA titers ≥1:8 and ≥1:128, but significantly lower rSBA GMTs and vaccine response rates for each serogroup in the MPS versus the noMPS group. MenACWY-TT had an acceptable safety profile in both groups. These results suggest that MenACWY-TT could be used in vaccination programs irrespective of the pre-vaccination status with polysaccharide vaccine. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

30 CFR 7.10 - MSHA acceptance of equivalent non-MSHA product safety standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false MSHA acceptance of equivalent non-MSHA product... General § 7.10 MSHA acceptance of equivalent non-MSHA product safety standards. (a) MSHA will accept non...) [Reserved] (d) After MSHA has determined that non-MSHA product safety standards are equivalent and has...

Two medical abortion regimens for late first-trimester termination of pregnancy: a prospective randomized trial.

PubMed

Dalenda, Chelly; Ines, Najar; Fathia, Boudaya; Malika, Affes; Bechir, Zouaoui; Ezzeddine, Sfar; Hela, Chelly; Badis, Channoufi Mohamed

2010-04-01

Medical abortion regimens based on the use of either misoprostol alone or in association with mifepristone have shown high efficacy and excellent safety profile in early pregnancy abortion. However, no clear recommendation is available for late first-trimester termination of pregnancy. A prospective randomized controlled trial included 122 women seeking medical abortion at 9 to 12 weeks of gestation. Seventy-three patients were given a fixed protocol of 200 mg of mifepristone followed 48 h later by 400 mcg oral misoprostol (Group 1). The second group of 49 patients was administered 800-mcg intravaginal single-dose misoprostol (Group 2). This study sought to compare safety, efficacy and acceptability of these two nonsurgical abortion regimens. Fifty-nine (80.8%) women in Group 1 had complete abortion vs. 38 (77.4%) women in Group 2 (p=.66). Abdominal pain was observed significantly more often in Group 2 (35/49 (71.4%) vs. 32/73 (43.8%) in Group 1, p<.0001. Medical abortion was equally acceptable among the two groups [37/49 (75.5%) and 55/73 (75.7%), p=.89]. For late first-trimester termination, a single 800-mcg vaginal dose of misoprostol seems to be as effective as the mifepristone+misoprostol regimen, with acceptable side effects. Copyright 2010 Elsevier Inc. All rights reserved.

Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China.

PubMed

Li, Rongcheng; Li, Chang Gui; Li, Yanping; Liu, Youping; Zhao, Hong; Chen, Xiaoling; Kuriyakose, Sherine; Van Der Meeren, Olivier; Hardt, Karin; Hezareh, Marjan; Roy-Ghanta, Sumita

2016-03-14

Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix™, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China. In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study. Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and ≥ 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in ≥ 94.7% IPV and ≥ 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration. Trivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

PubMed

Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

2015-12-01

We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers. This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination. Reactogenicity and safety were assessed, and vaccination-related serious adverse events were recorded from the time of primary vaccination. Before booster (year 4), 74.1%, 40.4%, 49.3% and 58.2% of MenACWY-TT-recipients retained rSBA titers ≥1:8 for serogroups A, C, W and Y, respectively; 28.8%, 73.2%, 80.6% and 65.4% retained hSBA ≥1:8. Percentages for the MenC-CRM group were 35.6% (rSBA-MenC) and 46.9% (hSBA-MenC). After MenACWY-TT booster, ≥99.5% had rSBA ≥1:8 and hSBA ≥1:8 for each serogroup. After MenC-CRM197 booster, all children had rSBA-MenC ≥1:8 and hSBA-MenC ≥1:8. At year 5, percentages above the cut-off were ≥97.4% (rSBA) and ≥95.5% (hSBA) in MenACWY-TT-vaccinees for each serogroup. The MenACWY-TT booster dose had a clinically acceptable safety profile. No vaccine-related serious adverse events were reported. There was evidence of antibody persistence 4 years after toddlers were primed with MenACWY-TT. Booster vaccination induced robust immune responses for all serogroups with an acceptable safety profile.

Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK-positive Non-Small Cell Lung Cancer.

PubMed

Yang, James Chih-Hsin; Ou, Sai-Hong Ignatius; De Petris, Luigi; Gadgeel, Shirish; Gandhi, Leena; Kim, Dong-Wan; Barlesi, Fabrice; Govindan, Ramaswamy; Dingemans, Anne-Marie C; Crino, Lucio; Lena, Herve; Popat, Sanjay; Ahn, Jin Seok; Dansin, Eric; Golding, Sophie; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Zeaiter, Ali; Shaw, Alice T

2017-10-01

Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy and safety data after 15 and 18 months more follow-up than in the respective primary analyses. Enrolled patients had ALK receptor tyrosine kinase gene (ALK)-positive NSCLC and had progressed while taking, or could not tolerate, crizotinib. Patients received oral alectinib, 600 mg twice daily. The primary end point in both studies was objective response rate assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included disease control rate, duration of response, progression-free survival, overall survival, and safety. The pooled data set included 225 patients (n = 138 in NP28673 and n = 87 in NP28761). The response-evaluable population included 189 patients (84% [n = 122 in NP28673 and n = 67 in NP28761]). In the response-evaluable population, objective response rate as assessed by the IRC was 51.3% (95% confidence interval [CI]: 44.0-58.6 [all PRs]), the disease control rate was 78.8% (95% CI: 72.3-84.4), and the median duration of response was 14.9 months (95% CI: 11.1-20.4) after 58% of events. Median progression-free survival as assessed by the IRC was 8.3 months (95% CI: 7.0-11.3) and median overall survival was 26.0 months (95% CI: 21.4-not estimable). Grade 3 or higher adverse events (AEs) occurred in 40% of patients, 6% of patients had treatment withdrawn on account of AEs, and 33% had AEs leading to dose interruptions/modification. This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Allogeneic blood stem cell transplantation: considerations for donors.

PubMed

Anderlini, P; Körbling, M; Dale, D; Gratwohl, A; Schmitz, N; Stroncek, D; Howe, C; Leitman, S; Horowitz, M; Gluckman, E; Rowley, S; Przepiorka, D; Champlin, R

1997-08-01

Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An "ad hoc" workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34+ progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection.

Manganese chloride tetrahydrate (CMC-001) enhanced liver MRI: evaluation of efficacy and safety in healthy volunteers.

PubMed

Albiin, Nils; Kartalis, Nikolaos; Bergquist, Annika; Sadigh, Bita; Brismar, Torkel B

2012-10-01

To evaluate the efficacy of three dose levels of the oral hepatobiliary manganese-based magnetic resonance imaging (MRI) contrast agent CMC-001, and assess its safety profile and patient acceptability. After ethics committee approval, 32 healthy volunteers (males/females: 18/14) were included. Liver MRI was performed before and 3 h after ingestion of 0.8, 0.4, and 0.2 g of CMC-001 on separate occasions. Liver-to-muscle signal intensity (SI) ratio from baseline to post-contrast and image quality was assessed. Adverse drug reactions/adverse events (ADRs/AEs) and clinico-laboratory tests were monitored. The increase in liver-to-muscle SI ratio was significantly higher after 0.8 g (0.696) compared to 0.4 g (0.458) and 0.2 g (0.223) (in all pair-wise comparisons, P < 0.0001). The overall image quality was superior after 0.8 g. ADRs/AEs were dose-related and predominantly of mild intensity. Liver MRI using 0.8 g CMC-001 has the highest efficacy and still acceptable ADRs and should therefore be preferred.

Safety of Lumbar Puncture Procedures in Patients with Alzheimer's Disease

PubMed Central

Peskind, E.; Nordberg, A.; Darreh-Shori, T.; Soininen, H.

2014-01-01

Changes in cerebrospinal fluid (CSF) biomarkers are representative of biochemical changes in the brain. Collection of CSF by lumbar puncture (LP) is essential for biomarker analysis, which is important for research in neurodegenerative disorders. However, LP for research purposes has been controversial due to a reported high incidence of severe LP headache when using standard 18g or 20g Quincke needles with a beveled cutting tip. A procedural safety analysis was performed using the database of a multicenter, 13-week study of CSF cholinesterase activity. A 24g Sprotte atraumatic needle was used to collect CSF at baseline and at Week 13 from 63 older patients with mild to moderate Alzheimer's disease. There was a < 2% LP headache incidence, and a favorable safety profile was reported. In conclusion, LP performed with a 24g Sprotte atraumatic needle (blunt, “bullet” tip) was a well-tolerated procedure, with good acceptability. PMID:19519311

Flight evaluation of two-segment approaches using area navigation guidance equipment

NASA Technical Reports Server (NTRS)

Schwind, G. K.; Morrison, J. A.; Nylen, W. E.; Anderson, E. B.

1976-01-01

A two-segment noise abatement approach procedure for use on DC-8-61 aircraft in air carrier service was developed and evaluated. The approach profile and procedures were developed in a flight simulator. Full guidance is provided throughout the approach by a Collins Radio Company three-dimensional area navigation (RNAV) system which was modified to provide the two-segment approach capabilities. Modifications to the basic RNAV software included safety protection logic considered necessary for an operationally acceptable two-segment system. With an aircraft out of revenue service, the system was refined and extensively flight tested, and the profile and procedures were evaluated by representatives of the airlines, airframe manufacturers, the Air Line Pilots Association, and the Federal Aviation Adminstration. The system was determined to be safe and operationally acceptable. It was then placed into scheduled airline service for an evaluation during which 180 approaches were flown by 48 airline pilots. The approach was determined to be compatible with the airline operational environment, although operation of the RNAV system in the existing terminal area air traffic control environment was difficult.

Ensuring the optimal safety of licensed vaccines: a perspective of the vaccine research, development, and manufacturing companies.

PubMed

Kanesa-thasan, Niranjan; Shaw, Alan; Stoddard, Jeffrey J; Vernon, Thomas M

2011-05-01

Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.

An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children.

PubMed

Knuf, Markus; Pantazi-Chatzikonstantinou, Anna; Pfletschinger, Ulrich; Tichmann-Schumann, Irmingard; Maurer, Hartwig; Maurer, Lothar; Fischbach, Thomas; Zinke, Henrike; Pankow-Culot, Heidemarie; Papaevangelou, Vassiliki; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

2011-06-06

Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥ 97.3% of ACWY-TT vaccinees had rSBA titres ≥ 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥ 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules. Copyright © 2011 Elsevier Ltd. All rights reserved.

Performing the Peace: Using Playback Theatre in the Strengthening of Police-Community Relations.

PubMed

Smigelsky, Melissa A; Neimeyer, Robert A; Murphy, Virginia; Brown, DeAndre; Brown, Vinessa; Berryhill, Anthony; Knowlton, Joy

Police-community relations have catapulted onto the national stage after several high-profile instances of alleged police brutality. Blame and hostility can be barriers to positive police-community relations. Playback is a form of audience-inspired, improvisational theater designed to promote connectivity and empathy through storytelling. We tested the feasibility and acceptability of an arts-based intervention, bringing together police officers and formerly incarcerated individuals from the same community in Memphis, Tennessee. We collected pre/post quantitative data from five police officers and five ex-offenders who took part in the intervention, as well as qualitative data to provide contextual information. The project was feasible and acceptable to participants. Participants showed gains in their ability to make meaning of stressful life experiences. The officers and ex-offenders showed parallel gains in their increased positive attitudes toward the other group. This study demonstrates that creating contexts of safety and understanding necessary to address relational problems is both feasible and acceptable to law enforcement and ex-offenders.

Growth of Escherichia coli O157:H7 and Listeria monocytogenes in packaged fresh-cut romaine mix at fluctuating temperatures during commercial transport, retail storage, and display.

PubMed

Zeng, Wenting; Vorst, Keith; Brown, Wyatt; Marks, Bradley P; Jeong, Sanghyup; Pérez-Rodríguez, Fernando; Ryser, Elliot T

2014-02-01

Temperature abuse during commercial transport and retail sale of leafy greens negatively impacts both microbial safety and product quality. Consequently, the effect of fluctuating temperatures on Escherichia coli O157:H7 and Listeria monocytogenes growth in commercially-bagged salad greens was assessed during transport, retail storage, and display. Over a 16-month period, a series of time-temperature profiles for bagged salads were obtained from five transportation routes covering four geographic regions (432 profiles), as well as during retail storage (4,867 profiles) and display (3,799 profiles). Five different time-temperature profiles collected during 2 to 3 days of transport, 1 and 3 days of retail storage, and 3 days of retail display were then duplicated in a programmable incubator to assess E. coli O157:H7 and L. monocytogenes growth in commercial bags of romaine lettuce mix. Microbial growth predictions using the Koseki-Isobe and McKellar-Delaquis models were validated by comparing the root mean square error (RMSE), bias, and the acceptable prediction zone between the laboratory growth data and model predictions. Monte Carlo simulations were performed to calculate the probability distribution of microbial growth from 8,122,127,472 scenarios during transport, cold room storage, and retail display. Using inoculated bags of retail salad, E. coli O157:H7 and L. monocytogenes populations increased a maximum of 3.1 and 3.0 log CFU/g at retail storage. Both models yielded acceptable RMSEs and biases within the acceptable prediction zone for E. coli O157:H7. Based on the simulation, both pathogens generally increased <2 log CFU/g during transport, storage, and display. However, retail storage duration can significantly impact pathogen growth. This large-scale U.S. study-the first using commercial time/temperature profiles to assess the microbial risk of leafy greens-should be useful in filling some of the data gaps in current risk assessments for leafy greens.

75 FR 77675 - AREVA NP, Inc.; Confirmatory Order (Effective Immediately)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-13

..., appropriate notification of regulatory authorities, safety culture and safety conscious work environment...., outside the global AREVA organization), safety culture assessment in accordance with an accepted nuclear....e., outside the global AREVA organization), safety culture assessment in accordance with an accepted...

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.

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.

Sitagliptin/Simvastatin: a first combination tablet to treat type 2 diabetes and hypercholesterolemia – a review of its characteristics

PubMed Central

Ramadan, Wijdan H; Kabbara, Wissam K

2015-01-01

Background The purpose of this study was to review the current literature and information on the combination product Juvisync™ (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011. Methods PubMed (2001–2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis. Conclusion Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sitagliptin is a good option for diabetic patients to improve glycemic control with a lower risk of hypoglycemia and weight gain. PMID:25709467

A Randomized Male Tolerance Study of Dapivirine Gel Following Multiple Topical Penile Exposures (MTN 012/IPM 010)

PubMed Central

Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W.; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M.

2014-01-01

Abstract Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be “very likely” to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug. PMID:24070431

A randomized male tolerance study of dapivirine gel following multiple topical penile exposures (MTN 012/IPM 010).

PubMed

Cranston, Ross D; Hoesley, Craig; Carballo-Diéguez, Alex; Hendrix, Craig W; Husnik, Marla; Levy, Lisa; Hall, Wayne; Soto-Torres, Lydia; Nel, Annalene M

2014-02-01

Dapivirine (DPV) is a nonnucleoside reverse transcriptase inhibitor with a favorable safety profile following vaginal application. A penile tolerance study was conducted prior to further development of DPV as a candidate vaginal microbicide. Twenty-four circumcised and 24 uncircumcised (N=48) healthy HIV-negative male participants aged 18 years or older were randomized 2:1:1 to apply DPV 0.05% gel, matched placebo gel, or universal placebo gel, respectively, to their penis once daily for 7 sequential days. The safety, acceptability, and pharmacokinetic profile of DPV 0.05% gel were assessed by the presence of Grade 2 or higher genitourinary adverse events (AEs) and systemic AEs, a behavioral questionnaire, and pharmacokinetic plasma blood draw, respectively, at the final clinic visit (FCV). There were no Grade 2 genitourinary AEs in 47 participants completing the FCV. One participant in the DPV arm failed to attend the FCV. There were 13 AEs reported; all were Grade 1 except one Grade 2 corneal laceration unrelated to study product. Participants liked the gel to a moderate extent, yet 72% reported they would be "very likely" to use a gel like the one they used in the study every time they have intercourse. DPV was detectable in plasma in all 23 DPV arm study participants at the FCV. On average, the circumcised participants' DPV concentrations were 54% of those in uncircumcised participants (p=0.07). Topical seven-day penile application of DPV 0.05% gel was locally and systemically safe, was acceptable to male participants, and resulted in systemic exposure to the drug.

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

PubMed

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

77 FR 10358 - Acceptance of ASTM F963-11 as a Mandatory Consumer Product Safety Standard

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Safety. Pursuant to section 106 of the Consumer Product Safety Improvement Act of 2008, ASTM F963-11 will... INFORMATION: On February 10, 2009, section 106(a) of the Consumer Product Safety Improvement Act of 2008... CONSUMER PRODUCT SAFETY COMMISSION 16 CFR Chapter II Acceptance of ASTM F963-11 as a Mandatory...

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.

Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

PubMed

Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

2016-05-05

In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. Published by Elsevier Ltd.

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

Immunogenicity, reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III, randomized, open-label, multicenter study.

PubMed

Lal, Himal; Poder, Airi; Campora, Laura; Geeraerts, Brecht; Oostvogels, Lidia; Vanden Abeele, Carline; Heineman, Thomas C

2018-01-02

In phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01 B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months. In this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2. 346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination. Immune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals. Clinicaltrials.gov (NCT01751165). Copyright © 2017. Published by Elsevier Ltd.

49 CFR 193.2303 - Construction acceptance.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service...

49 CFR 193.2303 - Construction acceptance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service...

Discovery of Tetralones as Potent and Selective Inhibitors of Acyl-CoA:Diacylglycerol Acyltransferase 1.

PubMed

Cheung, Mui; Tangirala, Raghuram S; Bethi, Sridhar R; Joshi, Hemant V; Ariazi, Jennifer L; Tirunagaru, Vijaya G; Kumar, Sanjay

2018-02-08

Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) plays an important role in triglyceride synthesis and is a target of interest for the treatment of metabolic disorders. Herein we describe the structure-activity relationship of a novel tetralone series of DGAT1 inhibitors and our strategies for overcoming genotoxic liability of the anilines embedded in the chemical structures, leading to the discovery of a candidate compound, ( S )-2-(6-(5-(3-(3,4-difluorophenyl)ureido)pyrazin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid (GSK2973980A, 26d ). Compound 26d is a potent and selective DGAT1 inhibitor with excellent DMPK profiles and in vivo efficacy in a postprandial lipid excursion model in mice. Based on the overall biological and developability profiles and acceptable safety profiles in the 7-day toxicity studies in rats and dogs, compound 26d was selected as a candidate compound for further development in the treatment of metabolic disorders.

16 CFR 1110.5 - Acceptable certificates.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Acceptable certificates. 1110.5 Section 1110.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CERTIFICATES OF COMPLIANCE § 1110.5 Acceptable certificates. A certificate that is in hard copy or electronic...

16 CFR 1110.5 - Acceptable certificates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Acceptable certificates. 1110.5 Section 1110.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CERTIFICATES OF COMPLIANCE § 1110.5 Acceptable certificates. A certificate that is in hard copy or electronic...

16 CFR 1110.5 - Acceptable certificates.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Acceptable certificates. 1110.5 Section 1110.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CERTIFICATES OF COMPLIANCE § 1110.5 Acceptable certificates. A certificate that is in hard copy or electronic...

16 CFR 1110.5 - Acceptable certificates.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Acceptable certificates. 1110.5 Section 1110.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CERTIFICATES OF COMPLIANCE § 1110.5 Acceptable certificates. A certificate that is in hard copy or electronic...

Dose-dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor.

PubMed

Jin, Yan; Regev, Arie; Kam, Jeanelle; Phipps, Krista; Smith, Claire; Henck, Judith; Campanale, Kristina; Hu, Leijun; Hall, D Greg; Yang, Xiao Yan; Nakano, Masako; McNearney, Terry Ann; Uetrecht, Jack; Landschulz, William

2018-01-01

LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety and tolerability profile. Healthy subjects were randomized to receive LY3031207 (25, 75 and 275 mg), placebo or celecoxib (400 mg) once daily for 28 days. The safety, tolerability and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated. The study was terminated when two subjects experienced drug-induced liver injury (DILI) after they had received 225 mg LY3031207 for 19 days. Liver biopsy from these subjects revealed acute liver injury with eosinophilic infiltration. Four additional DILI cases were identified after LY3031207 dosing had been stopped. All six DILI cases shared unique presentations of hepatocellular injury with hypersensitivity features and demonstrated a steep dose-dependent trend. Prompt discontinuation of the study drug and supportive medical care resulted in full recovery. Metabolites from metabolic activation of the imidazole ring were observed in plasma and urine samples from all subjects randomized to LY3031207 dosing. This study emphasized the importance of careful safety monitoring and serious adverse events management in phase I trials. Metabolic activation of the imidazole ring may be involved in the development of hepatotoxicity of LY3031207. © 2017 The British Pharmacological Society.

Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9 H -carbazole-1-carboxamide (BMS-935177)

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

De Lucca, George V.; Shi, Qing; Liu, Qingjie

Bruton’s tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure–activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.

Effects of disciplinary cultures of researchers and research trainees on the acceptability of nanocarriers for drug delivery in different contexts of use: a mixed-methods study

NASA Astrophysics Data System (ADS)

Chenel, Vanessa; Boissy, Patrick; Cloarec, Jean-Pierre; Patenaude, Johane

2015-04-01

The acceptability of nanomedical applications, which have the potential to generate ethical and societal impacts, is a significant factor in the deployment of nanomedicine. A lack of fit between nanomedical applications and society's values may result from a partial consideration of such impacts. New approaches for technological evaluation focused on impact perception, acceptance, and acceptability are needed to go beyond traditional technology assessment approaches used with nanotechnology, which focus mainly on toxicological and safety criteria. Using a new evaluative approach based on perceived impacts of nanotechnology, the objective of this study was to assess perceptions among researchers and research trainees familiar with emergent technologies and from different disciplinary background the scope of acceptability judgments made towards the use of nanocarriers. This mixed-methods study was based on scenarios presenting two types of drug-delivery nanocarriers (carbon, synthetic DNA) in two contexts of use (lung cancer treatment, seasonal flu treatment). Researchers and research trainees in the natural sciences and engineering, and the social sciences and the humanities were invited by email to take part in this project. An online questionnaire followed by semi-directed interviews allowed characterization of disciplinary divergences regarding to impact perception, acceptance, and acceptability of the scenarios. The results suggest that impact perception is influenced by disciplinary culture. Also, trends can be seen between respondents' profiles and variables of acceptance and acceptability, and certain components of the acceptability judgement are specific to each disciplinary culture. The acknowledgment and consideration of these disciplinary divergences could allow, among others, for opening up interdisciplinary dialogue on matters related to the acceptability of nanomedical applications and their developments.

Effects of disciplinary cultures of researchers and research trainees on the acceptability of nanocarriers for drug delivery in different contexts of use: a mixed-methods study.

PubMed

Chenel, Vanessa; Boissy, Patrick; Cloarec, Jean-Pierre; Patenaude, Johane

The acceptability of nanomedical applications, which have the potential to generate ethical and societal impacts, is a significant factor in the deployment of nanomedicine. A lack of fit between nanomedical applications and society's values may result from a partial consideration of such impacts. New approaches for technological evaluation focused on impact perception, acceptance, and acceptability are needed to go beyond traditional technology assessment approaches used with nanotechnology, which focus mainly on toxicological and safety criteria. Using a new evaluative approach based on perceived impacts of nanotechnology, the objective of this study was to assess perceptions among researchers and research trainees familiar with emergent technologies and from different disciplinary background the scope of acceptability judgments made towards the use of nanocarriers. This mixed-methods study was based on scenarios presenting two types of drug-delivery nanocarriers (carbon, synthetic DNA) in two contexts of use (lung cancer treatment, seasonal flu treatment). Researchers and research trainees in the natural sciences and engineering, and the social sciences and the humanities were invited by email to take part in this project. An online questionnaire followed by semi-directed interviews allowed characterization of disciplinary divergences regarding to impact perception, acceptance, and acceptability of the scenarios. The results suggest that impact perception is influenced by disciplinary culture. Also, trends can be seen between respondents' profiles and variables of acceptance and acceptability, and certain components of the acceptability judgement are specific to each disciplinary culture. The acknowledgment and consideration of these disciplinary divergences could allow, among others, for opening up interdisciplinary dialogue on matters related to the acceptability of nanomedical applications and their developments.

Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma.

PubMed

Hashmi, Mehmood H; Van Veldhuizen, Peter J

2010-05-01

In advanced renal cell cancer and malignant melanoma, the current FDA approved immune modulators, such as IL-2, are the only agents which provide a durable complete remission. These responses, however, occur in < 10% of treated patients and their applicability is limited to selected patients because of their toxicity. The identification of new immunotherapeutic agents with an improved response rate and toxicity profile would represent a significant advancement in the treatment of these malignancies. This is a comprehensive review of IL-21 including its pharmacology and current developmental status. A literature review was performed using all PubMed listed publications involving IL-21, including original research articles, reviews and abstracts. It also includes a review of current ongoing trials and information from the official product website. Recombinant IL-21 (rIL-21) is a new immune modulator currently undergoing Phase I and II testing. It is a cytokine with a four helix structure that has structural and sequence homology to IL-2 and -15, but also possesses many unique biological properties. In this review, we evaluate the development, pharmacologic properties, safety profile and current clinical efficacy of rIL-21. rIL-21 has an acceptable safety profile and encouraging single agent activity in early phase renal cell carcinoma and melanoma clinical trials.

Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15-18 Months of Age in Mexico: A Randomized Trial.

PubMed

Melo, Flor Irene Rodriguez; Morales, José Juan Renteria; De Los Santos, Abiel Homero Mascareñas; Rivas, Enrique; Vigne, Claire; Noriega, Fernando

2017-06-01

The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated. This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed. Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study. Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies.

PubMed

Giovannoni, Gavin; Kappos, Ludwig; Gold, Ralf; Khatri, Bhupendra O; Selmaj, Krzysztof; Umans, Kimberly; Greenberg, Steven J; Sweetser, Marianne; Elkins, Jacob; McCroskery, Peter

2016-09-01

Daclizumab has been evaluated in multicentre, randomised, double-blind studies for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). Safety and tolerability are key considerations in MS treatment selection, as they influence adherence to medication. Evaluate the safety of daclizumab in patients with RRMS from an integrated analysis of six clinical studies. Patients treated with at least one dose of subcutaneous daclizumab 150mg or 300mg monthly in three completed and three ongoing clinical studies were included in this integrated analysis. Cumulative incidence of treatment-emergent adverse events (AEs) was the primary endpoint. This analysis included 2236 patients with 5214 patient-years of exposure to daclizumab. The cumulative incidence of any AE was 84% and of any serious AE excluding MS relapse was 16%. The incidences of AEs when evaluated by 6-month intervals remained stable over the 6.5 years of maximum follow-up. Most AEs were mild or moderate in severity. An important safety concern associated with daclizumab therapy involved hepatic AEs (16%) and serum transaminase elevations at least three times the upper limit of normal (10%), most of which were asymptomatic, self-limiting, and non-recurring. Cumulative incidences of cutaneous, infectious, and gastrointestinal AEs were 33%, 59%, and 25%, respectively; most events either resolved spontaneously or were treated successfully with standard medical interventions and did not result in discontinuation of treatment. This integrated analysis demonstrates that treatment of RRMS with daclizumab for periods of up to 6.5 years is associated with an acceptable safety profile with no evidence of cumulative toxicity over time. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma.

PubMed

O'Byrne, Paul M; Jacques, Loretta; Goldfrad, Caroline; Kwon, Namhee; Perrio, Michael; Yates, Louisa J; Busse, William W

2016-11-24

Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients. Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical development programme in asthma. Safety data from 10 parallel-group, randomised, double-blind Phase II and III studies (including 3345 patients who received at least one dose of fluticasone furoate) were integrated to provide information on adverse events, withdrawals, laboratory assessments, vital signs and hypothalamic-pituitary-adrenal axis function. The efficacy of once-daily fluticasone furoate was evaluated in all included studies. Once-daily fluticasone furoate 100 μg and 200 μg safety profiles were consistent with those reported for other inhaled corticosteroids, and both doses consistently demonstrated efficacy versus placebo. In the integrated analysis, no dose-response relationship was observed for the overall incidence of adverse events and there were no significant effects of fluticasone furoate on hypothalamic-pituitary-adrenal axis function. Once-daily fluticasone furoate 100 μg and 200 μg had acceptable safety profiles and was efficacious in adult and adolescent patients with asthma. There was no evidence of cortisol suppression at studied doses. GSK (NCT01499446/FFA20001, NCT00398645/FFA106783, NCT00766090/112202, NCT00603746/FFA109684, NCT00603278/FFA109685, NCT00603382/FFA109687, NCT01436071/115283, NCT01436110/115285, NCT01159912/112059, NCT01431950/114496, NCT01165138/HZA106827, NCT01086384/106837, NCT01134042/HZA106829 and NCT01244984/1139879).

Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

PubMed

Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

PubMed Central

Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

16 CFR § 1110.5 - Acceptable certificates.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Acceptable certificates. § 1110.5 Section § 1110.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS CERTIFICATES OF COMPLIANCE § 1110.5 Acceptable certificates. A certificate that is in hard copy or electronic...

Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative review of efficacy, safety, patient preference, and cost.

PubMed

Herman, Howard

2007-01-01

The aim of this review was to compare the efficacy, safety, patient preference, and cost-effectiveness of once-daily budesonide aqueous nasal spray (BANS), fluticasone propionate nasal spray (FPNS), mometasone furoate nasal spray (MFNS), and triamcinolone aqueous nasal spray (TANS) for treatment of allergic rhinitis (AR) in adult patients. A MEDLINE search (1966 to January 2004) was conducted to identify potentially relevant English language articles. Pertinent abstracts from recent allergy society meetings were identified also. The medical subject heading search terms included were intranasal corticosteroid (INS), nasal steroid, BANS, MFNS, FPNS, or TANS and AR. Selected studies were randomized, controlled, comparison trials of patients with AR treated with once-daily BANS, MFNS, FPNS, or TANS. All four INSs administered once daily were effective and well tolerated in the treatment of AR in adult patients, with similar efficacy and adverse event profiles. No differences were seen between INSs in systemic effects, except for significantly lower overnight urinary cortisol levels in healthy volunteers treated with FPNS compared with placebo. Based on sensory attributes, patients preferred BANS and TANS versus MFNS and FPNS. BANS was associated with more days of treatment per prescription at a lower cost per day for adults compared with the other INSs and is the only INS with a pregnancy category B rating. BANS, FPNS, MFNS, and TANS have similar efficacy and safety profiles. Differences in sensory attributes, documented safety during pregnancy, and cost may contribute to better patient acceptance of one INS versus another and promote better adherence to therapy.

Pharmacokinetic Profiles of Ticagrelor Orodispersible Tablets in Healthy Western and Japanese Subjects.

PubMed

Teng, Renli; Hammarberg, Maria; Carlson, Glenn F; Bokelund-Singh, Sara; Ruderfelt, Terese; Blychert, Eva

2017-11-01

Ticagrelor is an antiplatelet agent for patients with acute coronary syndrome or a history of myocardial infarction. Two studies compared pharmacokinetic profiles of orodispersible (OD) ticagrelor tablets versus immediate-release (IR) tablets in Western and Japanese subjects. Both studies were open-label, randomized, crossover, single-center trials. Thirty-six healthy subjects (94% white, 6% other race; Western study NCT02400333) and 42 Japanese healthy subjects (Japanese study NCT02436577) received a single 90-mg ticagrelor dose as an OD tablet [with/without water, and via a nasogastric tube (Western study only)], and an IR tablet; washout between treatments was ≥7 days. Assessments included ticagrelor and AR-C124910XX (active metabolite) plasma concentrations for pharmacokinetic analyses, and safety evaluations. In the Western study, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for ticagrelor and AR-C124910XX maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) were within the acceptance interval (80%-125%) for OD tablets (with/without water, via a nasogastric tube) versus the IR tablet; except for an ~15% lowering of ticagrelor C max (90% CI: 76.77%-93.78%) for the OD tablet taken with water. In the Japanese study, 90% CIs of the GMRs for AUC and C max of both ticagrelor and AR-C124910XX were all within the acceptance intervals for the OD (with/without water) versus IR tablet. No new safety issues were identified. Ticagrelor administered as an OD tablet to Western (without water, and via a nasogastric tube) and Japanese (with/without water) subjects was bioequivalent to the IR tablet.

Prospective evaluation of 1-day polyethylene glycol-3350 bowel preparation regimen in children.

PubMed

Abbas, Mazen I; Nylund, Cade M; Bruch, Carol J; Nazareno, Luzviminda G; Rogers, Philip L

2013-02-01

The aim of the present study was to evaluate efficacy, safety, and tolerability of a pediatric colonoscopy bowel preparation regimen composed of polyethylene glycol-3350 (PEG-3350) and a sports drink completed in a few hours. A prospective, open-label trial of a colonoscopy bowel preparation in children ages 8 to 18 years that included 238 g of PEG-3350 mixed with 1.9 L of Gatorade completed in a few hours. Efficacy was determined using the Boston Bowel Preparation Scale. Basic metabolic profiles and questionnaires were obtained that assessed for safety, adverse effects, tolerability, and patient acceptability. Forty-six patients completed the study. Patients were predominately boys (56.5%) with a mean age of 14.50 years (SD ± 2.9 years). Forty-three (93.5%) were able to complete the regimen. All of the colonoscopies were completed to the cecum and 84% had terminal ileum visualization. Seventy-seven percent were found to be effective preparations. Nausea/vomiting were the most common reported adverse effect (60%) followed by abdominal pain/cramping (44%) and fatigue/weakness (40%). Overall, the regimen was acceptable with 1 exception being the large volume to drink. There were no clinically significant changes in basic metabolic profiles, although there was a statistically significant decrease in the mean potassium (0.16 mEq/L; P = 0.016), blood urea nitrogen (2.68 mg/dL; P < 0.0001), and carbon dioxide (1.89 mmol/L; P < 0.0001). This study demonstrated that PEG-3350 + Gatorade administered in a few hours is an effective, safe, and moderately tolerable bowel preparation regimen for colonoscopy in children.

49 CFR 232.505 - Pre-revenue service acceptance testing plan.

Code of Federal Regulations, 2013 CFR

2013-10-01

... acceptance tests; (3) Correct any safety deficiencies identified by FRA in the design of the equipment or in... principal test objectives shall be to demonstrate that the equipment meets the safety design and performance... 49 Transportation 4 2013-10-01 2013-10-01 false Pre-revenue service acceptance testing plan. 232...

49 CFR 232.505 - Pre-revenue service acceptance testing plan.

Code of Federal Regulations, 2012 CFR

2012-10-01

... acceptance tests; (3) Correct any safety deficiencies identified by FRA in the design of the equipment or in... principal test objectives shall be to demonstrate that the equipment meets the safety design and performance... 49 Transportation 4 2012-10-01 2012-10-01 false Pre-revenue service acceptance testing plan. 232...

49 CFR 232.505 - Pre-revenue service acceptance testing plan.

Code of Federal Regulations, 2014 CFR

2014-10-01

... acceptance tests; (3) Correct any safety deficiencies identified by FRA in the design of the equipment or in... principal test objectives shall be to demonstrate that the equipment meets the safety design and performance... 49 Transportation 4 2014-10-01 2014-10-01 false Pre-revenue service acceptance testing plan. 232...

49 CFR 232.505 - Pre-revenue service acceptance testing plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... acceptance tests; (3) Correct any safety deficiencies identified by FRA in the design of the equipment or in... principal test objectives shall be to demonstrate that the equipment meets the safety design and performance... 49 Transportation 4 2011-10-01 2011-10-01 false Pre-revenue service acceptance testing plan. 232...

Risk-Factor Profile of Living Kidney Donors: The Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry 2004-2012.

PubMed

Clayton, Philip A; Saunders, John R; McDonald, Stephen P; Allen, Richard D M; Pilmore, Helen; Saunder, Alan; Boudville, Neil; Chadban, Steven J

2016-06-01

Recent literature suggests that living kidney donation may be associated with an excess risk of end-stage kidney disease and death. Efforts to maximize access to transplantation may result in acceptance of donors who do not fit within current guidelines, potentially placing them at risk of adverse long-term outcomes. We studied the risk profile of Australian and New Zealand living kidney donors using data from the Australia and New Zealand Dialysis and Transplant Living Kidney Donor Registry over 2004 to 2012. We compared their predonation profile against national guidelines for donor acceptance. The analysis included 2,932 donors (mean age 48.8 ± 11.2 years, range 18-81), 58% female and 87% Caucasian. Forty (1%) had measured glomerular filtration rate less than 80 mL/min; 32 (1%) had proteinuria >300 mg/day; 589 (20%) were hypertensive; 495 (18%) obese; 9 (0.3%) were diabetic while a further 55 (2%) had impaired glucose tolerance; and 218 (7%) were current smokers. Overall 767 donors (26%) had at least one relative contraindication to donation and 268 (9%) had at least one absolute contraindication according to national guidelines. Divergence of current clinical practice from national guidelines has occurred. In the context of recent evidence demonstrating elevated long-term donor risk, rigorous follow-up and reporting of outcomes are now mandated to ensure safety and document any change in risk associated with such a divergence.

Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM.

PubMed

Moreau, Philippe; Chanan-Khan, Asher; Roberts, Andrew W; Agarwal, Amit B; Facon, Thierry; Kumar, Shaji; Touzeau, Cyrille; Punnoose, Elizabeth A; Cordero, Jaclyn; Munasinghe, Wijith; Jia, Jia; Salem, Ahmed Hamed; Freise, Kevin J; Leverson, Joel D; Enschede, Sari Heitner; Ross, Jeremy A; Maciag, Paulo C; Verdugo, Maria; Harrison, Simon J

2017-11-30

The antiapoptotic proteins BCL-2 and myeloid cell leukemia sequence 1 (MCL-1) promote multiple myeloma (MM) cell survival. Venetoclax is a selective, orally bioavailable small-molecule BCL-2 inhibitor; bortezomib can indirectly inhibit MCL-1. In preclinical studies, venetoclax enhanced bortezomib activity, suggesting that cotargeting of BCL-2 and MCL-1 could be an effective treatment strategy in myeloma. This phase 1b trial studied patients with relapsed/refractory MM receiving daily venetoclax (50-1200 mg per designated dose cohort; 800 mg in safety expansion) in combination with bortezomib and dexamethasone. A total of 66 patients were enrolled (54 in the dose-escalation cohorts and 12 in the safety expansion). Patients had received a median of 3 prior therapies (range, 1-13); 26 (39%) were refractory to prior bortezomib and 35 (53%) to lenalidomide; 39 (59%) had prior stem cell transplant. The combination was generally well tolerated, and common adverse events included mild gastrointestinal toxicities (diarrhea [46%], constipation [41%], and nausea [38%]) and grade 3/4 cytopenias (thrombocytopenia [29%] and anemia [15%]). The overall response rate (ORR) was 67% (44/66); 42% achieved very good partial response or better (≥VGPR). Median time to progression and duration of response were 9.5 and 9.7 months, respectively. ORR of 97% and ≥VGPR 73% were seen in patients not refractory to bortezomib who had 1 to 3 prior therapies. Patients with high BCL2 expression had a higher ORR (94% [17/18]) than patients with low BCL2 expression (59% [16/27]). This novel combination of venetoclax with bortezomib and dexamethasone has an acceptable safety profile and promising efficacy in patients with relapsed/refractory MM. This trial was registered at www.clinicaltrials.gov as #NCT01794507. © 2017 by The American Society of Hematology.

Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours

PubMed Central

Campone, M; Levy, V; Bourbouloux, E; Berton Rigaud, D; Bootle, D; Dutreix, C; Zoellner, U; Shand, N; Calvo, F; Raymond, E

2009-01-01

Everolimus displays antiproliferative effects on cancer cells, yields antiangiogenic activity in established tumours, and shows synergistic activity with paclitaxel in preclinical models. This study assessed the safety and the pharmacokinetic interactions of everolimus and paclitaxel in patients with advanced malignancies. Everolimus was dose escalated from 15 to 30 mg and administered with paclitaxel 80 mg m−2 on days 1, 8, and 15 every 28 days. Safety was assessed weekly, and dose-limiting toxicity (DLT) was evaluated in cycle 1. A total of 16 patients (median age 54.5 years, range 33–69) were entered; 11 had prior taxane therapy for breast (n=5), ovarian (n=3), and vaginal cancer (n=1) or angiosarcoma (n=2). Grade 3 neutropenia in six patients met the criteria for DLT in two patients receiving everolimus 30 mg weekly. Other drug-related grade 3 toxicities were leucopenia, anaemia, thrombocytopenia, stomatitis, asthenia, and increased liver enzymes. Tumour stabilisation reported in 11 patients exceeded 6 months in 2 patients with breast cancer. Everolimus showed an acceptable safety profile at the dose of 30 mg when combined with weekly paclitaxel 80 mg m−2, warranting further clinical investigation. PMID:19127256

Accepting managed aquifer recharge of urban storm water reuse: The role of policy-related factors

NASA Astrophysics Data System (ADS)

Mankad, Aditi; Walton, Andrea

2015-12-01

A between-groups experimental design examined public acceptance for managed aquifer recharge of storm water for indirect potable and nonpotable reuse; acceptance was based on five policy-related variables (fairness, effectiveness, trust, importance of safety assurances, and importance of communication activities). Results showed that public acceptance (N = 408) for managed aquifer recharge of storm water was higher for nonpotable applications, as was the importance of safety assurances. Analyses of variance also showed that perceptions of fairness and effectiveness were higher for a nonpotable scheme, but not trust. A three-step hierarchical regression (Step 1: age, gender, education, and income; Step 2: type of use; Step 3: fairness, effectiveness, trust, safety assurance, and communication activities) demonstrated that type of storm water use and the policy-related factors accounted for 73% of the variance in acceptance of storm water (R2 = 0.74, adjusted R2 = 0.74, F (10, 397) = 113.919, p < 0.001). Age, type of use, and three of the five policy-related factors were also significant individual predictors of acceptance. The most important predictors were perceptions of trust in water authorities, perceptions of effectiveness, and perceptions of fairness. Interestingly, while safety assurance was important in attitudinal acceptance of managed aquifer recharge based on type of use, safety assurance was not found to be significant predictor of acceptance. This research suggests that policy-makers should look to address matters of greater public importance and drive such as fairness, trust, and effectiveness of storm water programs and advocate these at the forefront of their policies, rather than solely on education campaigns.

A Prospective Randomized Controlled Trial of AJG522 versus Standard PEG + E as Bowel Preparation for Colonoscopy

PubMed Central

Sagawa, Toshihiko; Tomizawa, Taku; Mizuide, Masafumi; Yasuoka, Hidetoshi; Shimoyama, Yasuyuki; Kakizaki, Satoru; Kawamura, Osamu; Kusano, Motoyasu; Yamada, Masanobu

2015-01-01

Polyethylene glycol- (PEG-) based bowel preparations for colonoscopies are often poorly tolerated due to the large volumes of fluid intake required. We compared low-volume “modified” PEG + ascorbic acid (AJG522) with standard PEG with electrolytes (PEG + E) in addition to a stimulant laxative and an agent to improve bowel function for the bowel cleansing before colonoscopy to evaluate its efficacy, safety, and acceptability. Outpatients scheduled to undergo colonoscopy were randomized to receive either AJG522 or PEG + E. Bowel cleansing conditions were assessed via macroscopic fecal findings by blinded and independent investigators. A survey of the patients' feedback regarding the preparation was conducted by questionnaire. Successful cleansing was achieved in all cases, except for 4 cases in the PEG + E group, at 3 hours after taking the preparation. The fecal properties were significantly clearer in the AJG522 group than in the PEG + E group at 2 hours after taking each preparation (P = 0.013). Although the total liquid volume of the bowel preparation was not reduced, the AJG522 preparation could significantly reduce the required volume of the preparation (P < 0.0001). Moreover, the patients in the AJG522 group had better acceptability (P = 0.010). There were no significant differences in the safety profiles between groups (UMIN000013892). PMID:25688357

A multi-criteria decision making approach to identify a vaccine formulation.

PubMed

Dewé, Walthère; Durand, Christelle; Marion, Sandie; Oostvogels, Lidia; Devaster, Jeanne-Marie; Fourneau, Marc

2016-01-01

This article illustrates the use of a multi-criteria decision making approach, based on desirability functions, to identify an appropriate adjuvant composition for an influenza vaccine to be used in elderly. The proposed adjuvant system contained two main elements: monophosphoryl lipid and α-tocopherol with squalene in an oil/water emulsion. The objective was to elicit a stronger immune response while maintaining an acceptable reactogenicity and safety profile. The study design, the statistical models, the choice of the desirability functions, the computation of the overall desirability index, and the assessment of the robustness of the ranking are all detailed in this manuscript.

Assessing contextual factors that influence acceptance of pedestrian alerts by a night vision system.

PubMed

Källhammer, Jan-Erik; Smith, Kip

2012-08-01

We investigated five contextual variables that we hypothesized would influence driver acceptance of alerts to pedestrians issued by a night vision active safety system to inform the specification of the system's alerting strategies. Driver acceptance of automotive active safety systems is a key factor to promote their use and implies a need to assess factors influencing driver acceptance. In a field operational test, 10 drivers drove instrumented vehicles equipped with a preproduction night vision system with pedestrian detection software. In a follow-up experiment, the 10 drivers and 25 additional volunteers without experience with the system watched 57 clips with pedestrian encounters gathered during the field operational test. They rated the acceptance of an alert to each pedestrian encounter. Levels of rating concordance were significant between drivers who experienced the encounters and participants who did not. Two contextual variables, pedestrian location and motion, were found to influence ratings. Alerts were more accepted when pedestrians were close to or moving toward the vehicle's path. The study demonstrates the utility of using subjective driver acceptance ratings to inform the design of active safety systems and to leverage expensive field operational test data within the confines of the laboratory. The design of alerting strategies for active safety systems needs to heed the driver's contextual sensitivity to issued alerts.

Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F) nanoparticle vaccine in older adults.

PubMed

Fries, Louis; Shinde, Vivek; Stoddard, Jeffrey J; Thomas, D Nigel; Kpamegan, Eloi; Lu, Hanxin; Smith, Gale; Hickman, Somia P; Piedra, Pedro; Glenn, Gregory M

2017-01-01

A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. RSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.

Bully/Victim Profiles’ Differential Risk for Worsening Peer Acceptance: The Role of Friendship

PubMed Central

Kochel, Karen P.; Ladd, Gary W.; Bagwell, Catherine L.; Yabko, Brandon A.

2015-01-01

Study aims were to: (1) evaluate the association between bully/victim profiles, derived via latent profile analysis (LPA), and changes in peer acceptance from the fall to spring of 7th grade, and (2) investigate the likelihood of friendlessness, and the protective function of mutual friendship, among identified profiles. Participants were 2,587 7th graders; peer nomination and rating-scale data were collected in the fall and spring. Four profiles, including bullies, victims, bully-victims, and uninvolved adolescents, were identified at each time point. Findings showed that for victims, more so than for bullies and uninvolved profiles, acceptance scores worsened over time. Results further revealed that bully-victim and victim profiles included a greater proportion of friendless youth relative to the bully profile, which, in turn, contained a greater proportion of friendless adolescents than the uninvolved profile. Findings also provided evidence for the buffering role of friendship among all bully/victim profiles and among bully-victims especially. PMID:26309346

The effects, safety and acceptability of compact, pre-filled, autodisable injection devices when delivered by lay health workers.

PubMed

Glenton, Claire; Khanna, Rajesh; Morgan, Chris; Nilsen, Elin Strømme

2013-08-01

To systematically assess (i) the effects and safety and (ii) the acceptability of using lay health workers (LHWs) to deliver vaccines and medicines to mothers and children through compact pre-filled autodisable devices (CPADs). We searched electronic databases and grey literature. For the systematic review of effects and safety, we sought randomised and non-randomised controlled trials, controlled before-after studies and interrupted time series studies. For the systematic review of acceptability, we sought qualitative studies. Two researchers independently carried out data extraction, study quality assessment and thematic analysis of the qualitative data. No studies met our criteria for the review exploring the effects and safety of using LHWs to deliver CPADs. For the acceptability review, six qualitative studies assessed the acceptability of using LHWs to deliver hepatitis B vaccine, tetanus toxoid vaccine, gentamicin or oxytocin using Uniject™ devices. All studies took place in low- or middle-income countries and explored the perceptions of community members, LHWs, supervisors, health professionals or programme managers. Most of the studies were of low quality. Recipients generally accepted the intervention. Most health professionals were confident that LHWs could deliver the intervention with sufficient training and supervision, but some had problems delivering supervision. The LHWs perceived Uniject™ as effective and important and were motivated by positive responses from the community. However, some LHWs feared the consequences if harm should come to recipients. Evidence of the effects and safety of using CPADs delivered by LHWs is lacking. Evidence regarding acceptability suggests that this intervention may be acceptable although LHWs may feel vulnerable to blame. © 2013 John Wiley & Sons Ltd.

Efficacy and safety of valsartan/amlodipine single-pill combination in patients with essential hypertension (PEAK LOW).

PubMed

Kızılırmak, Pınar; Ar, Idilhan; Ilerigelen, Barış

2014-06-01

This study evaluated the efficacy as well as the safety and tolerability profile of low-dose valsartan/amlodipine (Val/Amlo) single-pill combination (SPC) (160/5 mg) in patients with essential hypertension in Turkey. Adult patients with essential hypertension [systolic blood pressure (SBP)>140 mmHg and/or diastolic blood pressure (DBP)>90 mmHg], who were on low dose Val/Amlo (160/5 mg) SPC before enrollment and gave informed consent, were accepted for this multi-centric observational study performed at 30 sites. The absolute changes in SBP and DBP from baseline were the primary efficacy outcomes. Safety assessments consisted of recording all adverse events. Of 381 patients enrolled, 327 completed the study; 39% were females. The mean age was 57.3±11.8 years. Median duration of hypertension was 38 months. Both SBP and DBP values showed reductions from 162.6±16.6 mmHg and 94.0±13.2 mmHg to 137.6±14.2 mmHg and 81.9±9.0 mmHg at 4th week and to 131.6±11.5 mmHg and 79.7±7.6 mmHg at 12th week, respectively. The control and response rates at the end of the study were 82.0% and 92.6%, respectively. Twelve patients (3.2%) experienced a total of 12 adverse events; there were no serious adverse events. The most common adverse event was edema (1.3%). Patient compliance was approximately 99%. Low-dose (160/5 mg) Val/Amlo SPC is efficacous and has a good tolerability and safety profile for the management of essential hypertension in Turkey.

49 CFR 193.2303 - Construction acceptance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Construction acceptance. 193.2303 Section 193.2303 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY LIQUEFIED NATURAL GAS FACILITIES...

Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance.

PubMed

Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

2015-03-01

This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice.

Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance

PubMed Central

Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

2015-01-01

This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. PMID:25838891

Active drug safety surveillance: a tool to improve public health.

PubMed

Platt, Richard; Madre, Leanne; Reynolds, Robert; Tilson, Hugh

2008-12-01

Ensuring that drugs have an acceptable safety profile and are used safely is a major public health priority. The Centers for Education and Research on Therapeutics (CERTs) convened experts from academia, government, and industry to assess strategies to increase the speed and predictive value of generating and evaluating safety signals, and to identify next steps to improve the US system for identifying and evaluating potential safety signals. The CERTs convened a think tank comprising representatives of the groups noted above to address these goals. Participants observed that, with the increasing availability of electronic health data, opportunities have emerged to more accurately characterize and confirm potential safety issues. The gain for public health from a highly coordinated network of population-based databases for active surveillance is great and within reach, although operational questions remain. A collaborative network must create a working definition of a safety signal, screening algorithms, and criteria and strategies to confirm or refute a signal once identified through screening. Guidelines are needed for when and how to communicate a signal exists and is being evaluated, as well as the outcome of that evaluation. A public-private partnership to create a network of government and private databases to routinely evaluate and prioritize safety questions is in the public interest. Better methods are needed, and a knowledgeable workforce is required to conduct the surveillance and understand how to interpret the results. The international community will benefit from the availability of better methods and more experts. Copyright (c) 2008 John Wiley & Sons, Ltd.

Overview of elagolix for the treatment of endometriosis.

PubMed

Melis, Gian Benedetto; Neri, Manuela; Corda, Valentina; Malune, Maria Elena; Piras, Bruno; Pirarba, Silvia; Guerriero, Stefano; Orrù, Marisa; D'Alterio, Maurizio Nicola; Angioni, Stefano; Paoletti, Anna Maria

2016-05-01

Suppression of sex-steroid secretion is required in a variety of gynecological conditions. This can be achieved using gonadotropin releasing hormone (GnRH) agonists that bind pituitary gonadotropin receptors and antagonize the link-receptor of endogenous GnRH, inhibiting the mechanism of GnRH pulsatility. On the other hand, GnRH antagonists immediately reduce gonadal steroid levels, avoiding the initial stimulatory phase of the agonists. Potential benefits of GnRH antagonists over GnRH agonists include a rapid onset and reversibility of action. Older GnRH antagonists are synthetic peptides, obtained by modifications of certain amino acids in the native GnRH sequence. They require subcutaneous injections, implantation of long-acting depots. The peptide structure is responsible for histamine-related adverse events and the tendency to elicit hypersensitivity reactions. Research has worked towards the development of non-peptidic molecules exerting antagonist action on GnRH. They are available for oral administration and may have a more beneficial safety profile in comparison with peptide GnRH antagonists. This article focuses on the data of the literature about elagolix, a novel non-peptidic GnRHantagonist, in the treatment of endometriosis. Elagolix demonstrated efficacy in the management of endometriosis-associated pain and had an acceptable safety and tolerability profile. However, further studies are necessary to evaluate its non-inferiority in comparison with other endometriosis's treatments.

Analysis of swine leukocyte antigen class I gene profiles and porcine endogenous retrovirus viremia level in a transgenic porcine herd inbred for xenotransplantation research

PubMed Central

Sypniewski, Daniel; Gałka, Sabina; Sołtysik, Dagna; Loch, Tomasz; Nowak, Ewa; Smorąg, Zdzisław; Bednarek, Ilona

2018-01-01

Molecular characterization of swine leukocyte antigen (SLA) genes is important for elucidating the immune responses between swine-donor and human-recipient in xenotransplantation. Examination of associations between alleles of SLA class I genes, type of pig genetic modification, porcine endogenous retrovirus (PERV) viral titer, and PERV subtypes may shed light on the nature of xenograft acceptance or rejection and the safety of xenotransplantation. No significant difference in PERV gag RNA level between transgenic and non-transgenic pigs was noted; likewise, the type of applied transgene had no impact on PERV viremia. SLA-1 gene profile type may correspond with PERV level in blood and thereby influence infectiveness. Screening of pigs should provide selection of animals with low PERV expression and exclusion of specimens with PERV-C in the genome due to possible recombination between A and C subtypes, which may lead to autoinfection. Presence of PERV-C integrated in the genome was detected in 31.25% of specimens, but statistically significant increased viremia in specimens with PERV-C was not observed. There is a need for multidirectional molecular characterization (SLA typing, viremia estimation, and PERV subtype screening) of animals intended for xenotransplantation research in the interest of xeno-recipient safety. PMID:29366300

ACCEPT 2: A public library of cluster properties

NASA Astrophysics Data System (ADS)

Donahue, Megan

2012-09-01

The current public ACCEPT database of cluster properties includes radial profiles of Tx, n_elec, entropy, and cooling time. We propose to more than double the current number of clusters in ACCEPT and to expand the current suite of properties to include uniformly measured profiles of gas mass and hydrostatic equilibrium mass along with signatures of dynamical relaxation (centroid shift, power ratios, surface brightness concentration, temperature ratios) and global quantities such as core-excised Tx, Lx, and metallicities. We will explore the relationship between cool cores and dynamical relaxation, the reliability of hydrostatic mass profiles, and the dependence of the gas mass fraction on halo mass, redshift, and the degree of relaxation. ACCEPT2 will enable further community science.

Students' Acceptance of Tablet PCs in Italian High Schools: Profiles and Differences

ERIC Educational Resources Information Center

Villani, Daniela; Morganti, Laura; Carissoli, Claudia; Gatti, Elena; Bonanomi, Andrea; Cacciamani, Stefano; Confalonieri, Emanuela; Riva, Giuseppe

2018-01-01

The tablet PC represents a very popular mobile computing device, and together with other technologies it is changing the world of education. This study aimed to explore the acceptance of tablet PC of Italian high school students in order to outline the typical students' profiles and to compare the acceptance conveyed in two types of use (learning…

Commercial grade item (CGI) dedication of generators for nuclear safety related applications

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

Das, R.K.; Hajos, L.G.

1993-03-01

The number of nuclear safety related equipment suppliers and the availability of spare and replacement parts designed specifically for nuclear safety related application are shrinking rapidly. These have made it necessary for utilities to apply commercial grade spare and replacement parts in nuclear safety related applications after implementing proper acceptance and dedication process to verify that such items conform with the requirements of their use in nuclear safety related application. The general guidelines for the commercial grade item (CGI) acceptance and dedication are provided in US Nuclear Regulatory Commission (NRC) Generic Letters and Electric Power Research Institute (EPRI) Report NP-5652,more » Guideline for the Utilization of Commercial Grade Items in Nuclear Safety Related Applications. This paper presents an application of these generic guidelines for procurement, acceptance, and dedication of a commercial grade generator for use as a standby generator at Salem Generating Station Units 1 and 2. The paper identifies the critical characteristics of the generator which once verified, will provide reasonable assurance that the generator will perform its intended safety function. The paper also delineates the method of verification of the critical characteristics through tests and provide acceptance criteria for the test results. The methodology presented in this paper may be used as specific guidelines for reliable and cost effective procurement and dedication of commercial grade generators for use as standby generators at nuclear power plants.« less

Patient-led training on patient safety: a pilot study to test the feasibility and acceptability of an educational intervention.

PubMed

Jha, V; Winterbottom, A; Symons, J; Thompson, Z; Quinton, N; Corrado, O J; Melville, C; Watt, I; Torgerson, D; Wright, J

2013-09-01

Training in patient safety is an important element of medical education. Most educational interventions on patient safety training adopt a 'health-professional lens' with limited consideration on the impact of safety lapses on the patient and their families and little or no involvement of patients in the design or delivery of the training. This paper describes a pilot study to test the feasibility and acceptability of implementing a patient-led educational intervention to facilitate safety training amongst newly qualified doctors. Patients and/or carers who had experienced harm during their care shared narratives of their stories with trainees; this was followed by a focused discussion on patient safety issues exploring the causes and consequences of safety incidents and lessons to be learned from these. The intervention, which will be further tested in an NIHR-funded randomised controlled trial (RCT), was successfully implemented into an existing training programme and found acceptance amongst the patients and trainees. The pilot study proved to be a useful step in refining the intervention for the RCT including identifying appropriate outcome measures and highlighting organisational issues.

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?

PubMed Central

Lazzari, Chiara; Karachaliou, Niki; Bulotta, Alessandra; Viganó, Mariagrazia; Mirabile, Aurora; Brioschi, Elena; Santarpia, Mariacarmela; Gianni, Luca; Rosell, Rafael; Gregorc, Vanesa

2018-01-01

Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy. The current review provides an overview on the molecular rationale for the investigation of combinatorial approaches with chemotherapy or radiotherapy. Moreover, the results of completed clinical studies will be reported. PMID:29662546

Current treatment recommendations and considerations for cryopyrin-associated periodic syndrome.

PubMed

Koné-Paut, Isabelle; Galeotti, Caroline

2015-01-01

Cryopyrin-associated periodic syndrome (CAPS) encompasses a spectrum of three phenotypes of increasing severity. The syndrome is due to dominant mutations in NLRP3, which encodes a key component of the innate immunity that regulates the secretion of IL-1β. CAPS manifests as systemic inflammation, which compromises quality of life and leads to serious complications and handicap. Anti-IL-1 drugs have shown remarkable efficacy in treating CAPS symptoms and have significantly changed patients' lives. They have acceptable safety profiles but do have some differences. We review three drugs that are currently marketed for CAPS, give additional information for the practical use of these drugs, and provide some recommendations for management.

Combination of immunotherapy with chemotherapy and radiotherapy in lung cancer: is this the beginning of the end for cancer?

PubMed

Lazzari, Chiara; Karachaliou, Niki; Bulotta, Alessandra; Viganó, Mariagrazia; Mirabile, Aurora; Brioschi, Elena; Santarpia, Mariacarmela; Gianni, Luca; Rosell, Rafael; Gregorc, Vanesa

2018-01-01

Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy. The current review provides an overview on the molecular rationale for the investigation of combinatorial approaches with chemotherapy or radiotherapy. Moreover, the results of completed clinical studies will be reported.

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 ...

Phase I / II study of brentuximab vedotin in Japanese patients with relapsed or refractory CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma

PubMed Central

Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Ishizawa, Kenichi; Uike, Naokuni; Uchida, Toshiki; Suzuki, Tatsuya; Aoki, Tomohiro; Watanabe, Takashi; Maruyama, Dai; Yokoyama, Masahiro; Takubo, Takatoshi; Kagehara, Hideaki; Matsushima, Takafumi

2014-01-01

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD30-positive Hodgkin's lymphoma or systemic anaplastic large-cell lymphoma, we carried out a phase I/II study. Brentuximab vedotin was given i.v. on day 1 of each 21-day cycle up to 16 cycles. In the phase I part of a dose-escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large-cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose-limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with Hodgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large-cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the Japanese population. This trial was registered in JAPIC Clinical Trials Information (JapicCTI-111650). This phase I/II study was to investigate the tolerability, safety and efficacy of brentuximab vedotin. This study indicates that 1.8 mg/kg brentuximab vedotin given every 3 weeks has a manageable safety profile and has high overall tumor response rate in Japanese patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma. PMID:24814862

Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

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

Yamshchikov, Vladimir, E-mail: yaximik@gmail.com

ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccinemore » candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.« less

Dietitians employed by health care facilities preferred a HACCP system over irradiation or chemical rinses for reducing risk of foodborne disease.

PubMed

Giamalva, J N; Redfern, M; Bailey, W C

1998-08-01

To survey dietitians in health care facilities about the acceptability of alternative meat and poultry processing methods designed to reduce the risk of foodborne disease and their willingness to pay for these processes. A geographically representative sample of 600 members of The American Dietetic Association who work in health care facilities. The response rate was 250 completed questionnaires from 592 eligible subjects (42%). A mail survey was used to gather information on the acceptability of a Hazard Analysis and Critical Control Point (HACCP) system, chemical rinses, and irradiation for increasing the safety of food. Discrete choice contingent valuation was used to determine the acceptability at current prices and at 5, 10, and 25 cents per pound above current prices. Logistic regression was used to estimate mean willingness to pay (the maximum amount respondents are willing to pay) for each process. A simultaneous equations regression model was used to estimate the effects of other variables on acceptability. Respondents expressed a high level of concern for food safety in health care facilities. The estimated mean willingness to pay was highest for a HACCP system and lowest for chemical rinses. The successful adoption of alternative methods to increase food safety depends on their acceptance by foodservice professionals. The professionals sampled were most accepting of a HACCP system, somewhat less accepting of irradiation, and least accepting of new chemical rinses. Poultry and beef processors and government agencies concerned with food safety may want to take into account the attitudes of foodservice professionals.

Development of the Consumer Refrigerator Safety Questionnaire: A Measure of Consumer Perceptions and Practices.

PubMed

Cairnduff, Victoria; Dean, Moira; Koidis, Anastasios

2016-09-01

Food preparation and storage behaviors in the home deviating from the "best practice" food safety recommendations may result in foodborne illnesses. Currently, there are limited tools available to fully evaluate the consumer knowledge, perceptions, and behavior in the area of refrigerator safety. The current study aimed to develop a valid and reliable tool in the form of a questionnaire, the Consumer Refrigerator Safety Questionnaire (CRSQ), for assessing systematically all these aspects. Items relating to refrigerator safety knowledge (n =17), perceptions (n =46), and reported behavior (n =30) were developed and pilot tested by an expert reference group and various consumer groups to assess face and content validity (n =20), item difficulty and consistency (n =55), and construct validity (n =23). The findings showed that the CRSQ has acceptable face and content validity with acceptable levels of item difficulty. Item consistency was observed for 12 of 15 in refrigerator safety knowledge. Further, all 5 of the subscales of consumer perceptions of refrigerator safety practices relating to risk of developing foodborne disease showed acceptable internal consistency (Cronbach's α value > 0.8). Construct validity of the CRSQ was shown to be very good (P = 0.022). The CRSQ exhibited acceptable test-retest reliability at 14 days with the majority of knowledge items (93.3%) and reported behavior items (96.4%) having correlation coefficients of greater than 0.70. Overall, the CRSQ was deemed valid and reliable in assessing refrigerator safety knowledge and behavior; therefore, it has the potential for future use in identifying groups of individuals at increased risk of deviating from recommended refrigerator safety practices, as well as the assessment of refrigerator safety knowledge and behavior for use before and after an intervention.

Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies.

PubMed

Belkoff, L; Brock, G; Carrara, D; Neijber, A; Ando, M; Mitchel, J

2018-02-01

Efficacy and safety of testosterone gel 2% (TG) were evaluated in two phase 3, open-labelled, single-arm, multicentre studies (000023 and extension study 000077). Hypogonadal men having serum testosterone levels <300 ng/dl at two consecutive measurements were included. Study duration was 9 months (000023: 3 months; 000077: 6 months). Starting dose of TG (46 mg) was applied on upper arm/shoulder. The primary endpoint (000023) was responder rate (subjects with average 24-hour serum testosterone concentration 300-1050 ng/dl on Day 90). Study 000077 evaluated the safety of TG in patients rolling over from study 000023 over a period of 6 months. Of 180 subjects in 000023, 172 completed and 145 rolled over to 000077, with 127 completers. The responder rate was 85.5%. Fewer subjects in 000077 (12.7%) versus 000023 (31.8%) had maximum testosterone concentration (C max ) >1500 ng/dl, with no significant safety concerns. Significant improvements in sexual function and quality of life were noted in both studies. Subjects experienced few skin reactions without notable increases in prostate-specific antigen and haematocrit levels. TG was efficacious with an acceptable safety profile. C max >1500 ng/dl did not exhibit distinct impact on safety parameters. However, further optimisation of titration schema to reduce C max is warranted while maintaining the average steady state total testosterone concentration. © 2017 Blackwell Verlag GmbH.

Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration.

PubMed

Moon, Sung-Hoon; Kim, Myung-Hwan; Park, Do Hyun; Song, Tae Joon; Eum, Junbum; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo

2010-07-01

Fully covered self-expandable metal stent (FCSEMS) placement has recently been tried in the management of refractory pancreatic-duct strictures associated with advanced chronic pancreatitis. The major limitation of FCSEMSs was frequent migration. To assess the safety, migration rate, and removability of modified FCSEMSs with antimigration features used for the treatment of benign pancreatic-duct strictures. Prospective study. Tertiary academic center. Thirty-two patients with chronic painful pancreatitis and dominant ductal stricture. Transpapillary endoscopic placement of FCSEMSs in the pancreatic duct with removal after 3 months. Technical and functional success and adverse events associated with the placement of metal stents. FCSEMSs were successfully placed in all patients through the major (n = 27) or minor (n = 5) duodenal papilla. All patients achieved pain relief from stent placement. There was no occurrence of stent-induced pancreatitis or pancreatic sepsis. No stent migrated, and all stents were easily removed. Follow-up ERCP 3 months after stent placement showed resolution of duct strictures in all patients. Pancreatograms obtained at FCSEMS removal displayed de novo focal pancreatic duct strictures in 5 patients, but all were asymptomatic. No long-term follow-up. Temporary 3-month placement of FCSEMSs was effective in resolving pancreatic-duct strictures in chronic pancreatitis, with an acceptable morbidity profile. Modified FCSEMSs can prevent stent migration, but may be associated with de novo duct strictures. Further trials are needed to assess long-term safety and efficacy. Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

75 FR 44046 - Noise Exposure Map Acceptance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... Airport (PHL) under the provisions of 49 U.S.C. 47501 et seq. (Aviation Safety and Noise Abatement Act... June 1, 2010. Under 49 U.S.C. Section 47503 of the Aviation Safety and Noise Abatement Act (hereinafter... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Noise Exposure Map Acceptance ACTION...

76 FR 6453 - Raynor Marketing, Ltd., Provisional Acceptance of a Settlement Agreement and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... CONSUMER PRODUCT SAFETY COMMISSION [CPSC Docket No. 11-C0003] Raynor Marketing, Ltd., Provisional...(e). Published below is a provisionally-accepted Settlement Agreement with Raynor Marketing, Ltd..., Raynor Marketing, Ltd. and the staff (``Staff'') of the United States Consumer Product Safety Commission...

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
.

PubMed

Brumbaugh Paradis, Heather; Alter, Debbie; Llerandi, Diane

2017-10-01

Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
. The aim was to describe treatment management considerations when caring for patients using venetoclax.
. A review was done of safety and management considerations based on current clinical practice and 240 patients with CLL who received venetoclax monotherapy on clinical trials from 2011-2016.
. Common adverse events were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. Because of rapid tumor reduction with venetoclax, nurses should be aware of the potential for tumor lysis syndrome (TLS) and the need to educate patients on steps to minimize risks, including gradual dose ramp-up, adequate hydration, and use of prophylactic antihyperuricemia agents. Following implementation of these risk-reducing measures, no clinical TLS events were reported in ongoing trials.

Use of tocilizumab in systemic sclerosis: A brief literature review.

PubMed

Fernández-Codina, A; Fernández-Fernández, J; Fernández-Pantiga, A

2018-03-27

The available treatments for systemic sclerosis (SS) have limited effectiveness. Treatment with tocilizumab (TCZ), a biological drug that inhibits interleukin 6 (IL-6), has recently been proposed. In this study, we conducted a literature review to assess the safety and efficacy of TCZ in SS. We found 52 articles, 10 of which we selected after evaluating the articles. In a randomised clinical trial, TCZ showed a nonsignificant improvement in the degree of skin induration, while another observational study showed neutral results. In this same clinical trial, the functional respiratory parameters showed a certain degree of stabilization. The safety profile of TCZ is acceptable; however, the current evidence regarding treatment of SS with TCZ is highly limited, although the drug could have a beneficial effect in skin disorder. New clinical trials are needed to determine the usefulness of TCZ in SS. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Safety and Efficacy of Gene Transfer for Leber’s Congenital Amaurosis

PubMed Central

Maguire, Albert M.; Simonelli, Francesca; Pierce, Eric A.; Pugh, Edward N.; Mingozzi, Federico; Bennicelli, Jeannette; Banfi, Sandro; Marshall, Kathleen A.; Testa, Francesco; Surace, Enrico M.; Rossi, Settimio; Lyubarsky, Arkady; Arruda, Valder R.; Konkle, Barbara; Stone, Edwin; Sun, Junwei; Jacobs, Jonathan; Dell’Osso, Lou; Hertle, Richard; Ma, Jian-xing; Redmond, T. Michael; Zhu, Xiaosong; Hauck, Bernd; Zelenaia, Olga; Shindler, Kenneth S.; Maguire, Maureen G.; Wright, J. Fraser; Volpe, Nicholas J.; McDonnell, Jennifer Wellman; Auricchio, Alberto; High, Katherine A.; Bennett, Jean

2010-01-01

SUMMARY Leber’s congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium–specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA. PMID:18441370

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.

Integration of safety technologies into rheumatology and orthopedics practices: a randomized, controlled trial.

PubMed

Moorjani, Gautam R; Bedrick, Edward J; Michael, Adrian A; Peisajovich, Andres; Sibbitt, Wilmer L; Bankhurst, Arthur D

2008-07-01

To identify and integrate new safety technologies into outpatient musculoskeletal procedures and measure the effect on outcome, including pain. Using national resources for patient safety and literature review, the following safety technologies were identified: a safety needle to reduce inadvertent needlesticks to heath care workers, and the reciprocating procedure device (RPD) to improve patient safety and reduce pain. Five hundred sixty-six musculoskeletal procedures involving syringes and needles were randomized to either an RPD group or a conventional syringe group, and pain, quality, safety, and physician acceptance were measured. During 566 procedures, no accidental needlesticks occurred with safety needles. Use of the RPD resulted in a 35.4% reduction (95% confidence interval [95% CI] 24-46%) in patient-assessed pain (mean +/- SD scores on a visual analog pain scale [VAPS] 3.12 +/- 2.23 for the RPD and 4.83 +/- 3.22 for the conventional syringe; P < 0.001) and a 49.5% reduction (95% CI 34-64%) in patient-assessed significant pain (VAPS score > or =5) (P < 0.001). Physician acceptance of the RPD combined with a safety needle was excellent. As mandated by the Joint Commission and the Occupational Safety and Health Administration, safety technologies and the use of pain scales can be successfully integrated into rheumatologic and orthopedic procedures. The combination of a safety needle to reduce needlestick injuries to health care workers and the RPD to improve safety and outcome of patients is effective and well accepted by physicians.

Cereal bars produced with banana peel flour: evaluation of acceptability and sensory profile.

PubMed

Carvalho, Vania Silva; Conti-Silva, Ana Carolina

2018-01-01

A mixture design was used to investigate the effects of banana peel flour, rice flakes and oat flour on sensory acceptability of cereal bars, with subsequent evaluation of sensory profile of products identified as having high acceptability. Regions of greater response for acceptability of the cereal bars, which are dependent on the three investigated components, were found. Although having good acceptability, sensory profiles of cereal bars were different. A cereal bar with the lowest quantity of banana peel flour was described as having a higher amount of rice flakes, chewiness and crispness, while formulations with intermediate and highest quantities of banana peel flour were described by darker color, higher banana aroma and bitter taste. Contrary to expectations, banana flavor of cereal bar with highest quantity of banana peel flour was lower than cereal bars with intermediate quantities. Cereal bars were not different in terms of hardness and adhesiveness and they also had a similar sweet taste and oat flavor. The use of banana peel flour in production of cereal bars is feasible and, even with different sensory profiles, cereal bars with banana peel flour are acceptable, which may favor the development of new products for different market niches. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study.

PubMed

Ruperto, Nicolino; Brunner, Hermine I; Zuber, Zbigniew; Tzaribachev, Nikolay; Kingsbury, Daniel J; Foeldvari, Ivan; Horneff, Gerd; Smolewska, Elzbieta; Vehe, Richard K; Hazra, Anasuya; Wang, Rong; Mebus, Charles A; Alvey, Christine; Lamba, Manisha; Krishnaswami, Sriram; Stock, Thomas C; Wang, Min; Suehiro, Ricardo; Martini, Alberto; Lovell, Daniel J

2017-12-28

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated. Twenty-six patients (age range 2-17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUC tau ) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; C max (ng/mL) was 47.0, 41.7, and 66.2, respectively. C trough , C min , and t 1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to C max (T max ) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed. PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program. ClinicalTrials.gov: NCT01513902 .

49 CFR 238.603 - Safety planning requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... acceptable level using a formal safety methodology such as MIL-STD-882; and (4) Impose operational... using a formal safety methodology such as MIL-STD-882; (5) Monitor the progress in resolving safety...

49 CFR 238.603 - Safety planning requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... acceptable level using a formal safety methodology such as MIL-STD-882; and (4) Impose operational... using a formal safety methodology such as MIL-STD-882; (5) Monitor the progress in resolving safety...

41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

Code of Federal Regulations, 2014 CFR

2014-01-01

... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

Code of Federal Regulations, 2012 CFR

2012-01-01

... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

Code of Federal Regulations, 2013 CFR

2013-07-01

... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

Code of Federal Regulations, 2011 CFR

2011-01-01

... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

41 CFR 102-80.125 - Who has the responsibility for determining the acceptability of each equivalent level of safety...

Code of Federal Regulations, 2010 CFR

2010-07-01

... departments or other local authorities for use in developing pre-fire plans. ... Fire Prevention Equivalent Level of Safety Analysis § 102-80.125 Who has the responsibility for... acceptability must include a review of the fire protection engineer's qualifications, the appropriateness of the...

Occupational Therapy and Sensory Integration for Children with Autism: A Feasibility, Safety, Acceptability and Fidelity Study

ERIC Educational Resources Information Center

Schaaf, Roseann C.; Benevides, Teal W.; Kelly, Donna; Mailloux-Maggio, Zoe

2012-01-01

Objective: To examine the feasibility, safety, and acceptability of a manualized protocol of occupational therapy using sensory integration principles for children with autism. Methods: Ten children diagnosed with autism spectrum disorder ages 4-8 years received intensive occupational therapy intervention using sensory integration principles…

Changing drivers' intentions and behaviours using fear-based driver fatigue advertisements.

PubMed

Tay, Richard; Watson, Barry

2002-01-01

This paper examines the effects of fear arousal and perceived efficacy on the acceptance and rejection of road safety advertising messages that are typical in Australia and New Zealand. Our results suggest that the level of fear arousal could be lowered without a significant effect on the message acceptance rates but could result in a lower rate of message rejection. Our results also suggest that the inclusion of explicit coping strategies in the road safety advertisements has a significant positive effect on message acceptance.

Chemical characteristics and volatile profile of genetically modified peanut cultivars.

PubMed

Ng, Ee Chin; Dunford, Nurhan T; Chenault, Kelly

2008-10-01

Genetic engineering has been used to modify peanut cultivars for improving agronomic performance and pest resistance. Food products developed through genetic engineering have to be assessed for their safety before approval for human consumption. Preservation of desirable chemical, flavor and aroma attributes of the peanut cultivars during the genetic modifications is critical for acceptance of genetically modified peanuts (GMP) by the food industry. Hence, the main objective of this study is to examine chemical characteristics and volatile profile of GMP. The genetically modified peanut cultivars, 188, 540 and 654 were obtained from the USDA-ARS in Stillwater, Oklahoma. The peanut variety Okrun was examined as a control. The volatile analysis was performed using a gas chromatograph/mass spectrometer (GC/MS) equipped with an olfactory detector. The peanut samples were also analyzed for their moisture, ash, protein, sugar and oil compositions. Experimental results showed that the variations in nutritional composition of peanut lines examined in this study were within the values reported for existing cultivars. There were minor differences in volatile profile among the samples. The implication of this study is significant, since it shows that peanut cultivars with greater pest and fungal resistance were successfully developed without major changes in their chemical characteristics.

Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer.

PubMed

Costa, Rubens Barros; Costa, Ricardo L B; Talamantes, Sarah M; Kaplan, Jason B; Bhave, Manali A; Rademaker, Alfred; Miller, Corinne; Carneiro, Benedito A; Mahalingam, Devalingam; Chae, Young Kwang

2018-04-24

Anaplastic lymphoma kinase ( ALK ) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.

Assessing Children's Perceptions of Academic Interventions: The Kids Intervention Profile

ERIC Educational Resources Information Center

Eckert, Tanya L.; Hier, Bridget O.; Hamsho, Narmene F.; Malandrino, Rigby D.

2017-01-01

The psychometric properties of the Kids Intervention Profile (KIP), a rating scale designed to measure academic intervention acceptability from the perspective of students, were examined as well as the influence of background factors on students' acceptability ratings. Data were extracted from 4 randomized controlled trials investigating the…

Public acceptability of highway safety countermeasures : volume IV, pedestrian measures.

DOT National Transportation Integrated Search

1981-06-01

This volume is part of a larger study providing information about public attitudes : towards proposed highway safety countermeasures in three program areas: alcohol : and drugs, unsafe driving behaviors, and pedestrian safety. Pedestrian safety : cou...

Acceptance threshold hypothesis is supported by chemical similarity of cuticular hydrocarbons in a stingless bee, Melipona asilvai.

PubMed

Nascimento, D L; Nascimento, F S

2012-11-01

The ability to discriminate nestmates from non-nestmates in insect societies is essential to protect colonies from conspecific invaders. The acceptance threshold hypothesis predicts that organisms whose recognition systems classify recipients without errors should optimize the balance between acceptance and rejection. In this process, cuticular hydrocarbons play an important role as cues of recognition in social insects. The aims of this study were to determine whether guards exhibit a restrictive level of rejection towards chemically distinct individuals, becoming more permissive during the encounters with either nestmate or non-nestmate individuals bearing chemically similar profiles. The study demonstrates that Melipona asilvai (Hymenoptera: Apidae: Meliponini) guards exhibit a flexible system of nestmate recognition according to the degree of chemical similarity between the incoming forager and its own cuticular hydrocarbons profile. Guards became less restrictive in their acceptance rates when they encounter non-nestmates with highly similar chemical profiles, which they probably mistake for nestmates, hence broadening their acceptance level.

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

Acceptability of text messages for safety netting patients with low-risk cancer symptoms: a qualitative study.

PubMed

Hirst, Yasemin; Lim, Anita Wey Wey

2018-05-01

Safety netting is an important diagnostic strategy for patients presenting to primary care with potential (low-risk) cancer symptoms. Typically, this involves asking patients to return if symptoms persist. However, this relies on patients re-appraising their symptoms and making follow-up appointments, which could contribute to delays in diagnosis. Text messaging is increasingly used in primary care to communicate with patients, and could be used to improve safety netting. To explore the acceptability and feasibility of using text messages to safety net patients presenting with low-risk cancer symptoms in GP primary care (txt-netting). Qualitative focus group and interview study with London-based GPs. Participants were identified using convenience sampling methods. Five focus groups and two interviews were conducted with 22 GPs between August and December 2016. Sessions were audiorecorded, transcribed verbatim, and analysed using thematic analysis. GPs were amenable to the concept of using text messages in cancer safety netting, identifying it as an additional tool that could help manage patients and promote symptom awareness. There was wide variation in GP preferences for text message content, and a number of important potential barriers to txt-netting were identified. Concerns were raised about the difficulties of conveying complex safety netting advice within the constraints of a text message, and about confidentiality, widening inequalities, and workload implications. Text messages were perceived to be an acceptable potential strategy for safety netting patients with low-risk cancer symptoms. Further work is needed to ensure it is cost-effective, user friendly, confidential, and acceptable to patients. © British Journal of General Practice 2018.

Comparative evaluation of different medication safety measures for the emergency department: physicians' usage and acceptance of training, poster, checklist and computerized decision support.

PubMed

Sedlmayr, Brita; Patapovas, Andrius; Kirchner, Melanie; Sonst, Anja; Müller, Fabian; Pfistermeister, Barbara; Plank-Kiegele, Bettina; Vogler, Renate; Criegee-Rieck, Manfred; Prokosch, Hans-Ulrich; Dormann, Harald; Maas, Renke; Bürkle, Thomas

2013-07-29

Although usage and acceptance are important factors for a successful implementation of clinical decision support systems for medication, most studies only concentrate on their design and outcome. Our objective was to comparatively investigate a set of traditional medication safety measures such as medication safety training for physicians, paper-based posters and checklists concerning potential medication problems versus the additional benefit of a computer-assisted medication check. We concentrated on usage, acceptance and suitability of such interventions in a busy emergency department (ED) of a 749 bed acute tertiary care hospital. A retrospective, qualitative evaluation study was conducted using a field observation and a questionnaire-based survey. Six physicians were observed while treating 20 patient cases; the questionnaire, based on the Technology Acceptance Model 2 (TAM2), has been answered by nine ED physicians. During field observations, we did not observe direct use of any of the implemented interventions for medication safety (paper-based and electronic). Questionnaire results indicated that the electronic medication safety check was the most frequently used intervention, followed by checklist and posters. However, despite their positive attitude, physicians most often stated that they use the interventions in only up to ten percent for subjectively "critical" orders. Main reasons behind the low usage were deficits in ease-of-use and fit to the workflow. The intention to use the interventions was rather high after overcoming these barriers. Methodologically, the study contributes to Technology Acceptance Model (TAM) research in an ED setting and confirms TAM2 as a helpful diagnostic tool in identifying barriers for a successful implementation of medication safety interventions. In our case, identified barriers explaining the low utilization of the implemented medication safety interventions - despite their positive reception - include deficits in accessibility, briefing for the physicians about the interventions, ease-of-use and compatibility to the working environment.

Comparative evaluation of different medication safety measures for the emergency department: physicians’ usage and acceptance of training, poster, checklist and computerized decision support

PubMed Central

2013-01-01

Background Although usage and acceptance are important factors for a successful implementation of clinical decision support systems for medication, most studies only concentrate on their design and outcome. Our objective was to comparatively investigate a set of traditional medication safety measures such as medication safety training for physicians, paper-based posters and checklists concerning potential medication problems versus the additional benefit of a computer-assisted medication check. We concentrated on usage, acceptance and suitability of such interventions in a busy emergency department (ED) of a 749 bed acute tertiary care hospital. Methods A retrospective, qualitative evaluation study was conducted using a field observation and a questionnaire-based survey. Six physicians were observed while treating 20 patient cases; the questionnaire, based on the Technology Acceptance Model 2 (TAM2), has been answered by nine ED physicians. Results During field observations, we did not observe direct use of any of the implemented interventions for medication safety (paper-based and electronic). Questionnaire results indicated that the electronic medication safety check was the most frequently used intervention, followed by checklist and posters. However, despite their positive attitude, physicians most often stated that they use the interventions in only up to ten percent for subjectively “critical” orders. Main reasons behind the low usage were deficits in ease-of-use and fit to the workflow. The intention to use the interventions was rather high after overcoming these barriers. Conclusions Methodologically, the study contributes to Technology Acceptance Model (TAM) research in an ED setting and confirms TAM2 as a helpful diagnostic tool in identifying barriers for a successful implementation of medication safety interventions. In our case, identified barriers explaining the low utilization of the implemented medication safety interventions - despite their positive reception - include deficits in accessibility, briefing for the physicians about the interventions, ease-of-use and compatibility to the working environment. PMID:23890121

The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine.

PubMed

Gilca, Vladimir; Sauvageau, Chantal; Boulianne, Nicole; De Serres, Gatson; Crajden, Mel; Ouakki, Manale; Trevisan, Andrea; Dionne, Marc

2015-01-01

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

The perception of children's computer-imaged facial profiles by patients, mothers and clinicians.

PubMed

Miner, Robert M; Anderson, Nina K; Evans, Carla A; Giddon, Donald B

2007-11-01

To demonstrate the usefulness of a new imaging system for comparing the morphometric bases of children's self-perception of their facial profile with the perceptions of their mothers and treating clinicians. Rather than choosing among a series of static images, a computer imaging program was developed to elicit a range of acceptable responses or tolerance for change from which a midpoint of acceptability was derived. Using the method of Giddon et al, three profile features (upper and lower lips and mandible) from standardized images of 24 patients aged 8- 15 years were distorted and presented to patients, parents, and clinicians in random order as slowly moving images (four frames per second) from retrusive and protrusive extremes. Subjects clicked the mouse when the image became acceptable and released it when it was no longer acceptable. Subjects responded similarly to a neutral facial profile. Patients and their mothers overestimated the protrusiveness of the mandible of the actual pretreatment profile. Consistent with related studies, mothers had a smaller tolerance for change in the soft tissue profile than the children or clinicians. The magnitudes of the children's self-preference and preferred change in a neutral face were also significantly correlated. Both patients and mothers preferred a more protrusive profile than that of the actual or neutral face for the patient and neutral face. Imaging software can be used with children to compare their preferences with those of parents and clinicians to facilitate treatment planning and patient satisfaction.

Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy.

PubMed

Iftikhar, Imran H; Alghothani, Lana; Sardi, Alejandro; Berkowitz, David; Musani, Ali I

2017-07-01

Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video-assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two-by-two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9-88.8%), 87% (85-89%), and 57% (40-73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6-95.8%), 91.0% (89-92%), and 58% (31-81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post-procedural pneumothorax was 4.9% (2.2-10.7%) and 9.5% (5.9-14.9%), respectively. Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases.

Dacarbazine in combination with bevacizumab for the treatment of unresectable/metastatic melanoma: a phase II study.

PubMed

Ferrucci, Pier F; Minchella, Ida; Mosconi, Massimo; Gandini, Sara; Verrecchia, Francesco; Cocorocchio, Emilia; Passoni, Claudia; Pari, Chiara; Testori, Alessandro; Coco, Paola; Munzone, Elisabetta

2015-06-01

The combined treatment of dacarbazine with an antiangiogenic drug such as bevacizumab may potentiate the therapeutic effects of dacarbazine in metastatic melanoma (MM). Preliminary antitumour activity of dacarbazine plus bevacizumab is evaluated, together with the toxicity and safety profile, in MM patients. This prospective, open-label, phase II study included patients with previously untreated MM or unresectable melanoma. Patients received dacarbazine and bevacizumab until progressive disease or unacceptable toxicity. The primary efficacy variable was the overall response rate. The secondary efficacy parameters included duration of response, duration of stable disease, time to progression/progression-free survival, time to treatment failure and overall survival. The safety analysis included recordings of adverse events and exposure to study treatment. The intention-to-treat population included 37 patients (24 men and 13 women, mean age 54.2±13.1 years). Overall response rate was 18.9% (seven patients achieved a response) and clinical benefit was 48.6%. In patients who achieved a response, the median duration of response was 16.9 months and the median duration of stable disease was 12.5 months. The median time to progression/progression-free survival and time to treatment failure were 5.5 and 3.1 months, respectively. The median overall survival was 11.4 months. Almost all patients (94.6%) experienced at least one adverse event; however, no new area of toxicity of bevacizumab emerged. The dacarbazine/bevacizumab combination provides benefits compared with dacarbazine monotherapy in historical controls, with an acceptable safety profile. This combination appears to be a valid option in specific subgroups of patients, namely, those triple negative (BRAF, C-KIT and NRAS wild type) or with a BRAF mutation who have already received, or are not eligible for, immunomodulating or targeted agents.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

PubMed

Minervini, Gianmaria; McCarson, Barbara J; Reisinger, Keith S; Martin, Jason C; Stek, Jon E; Atkins, Barbara M; Nadig, Karin B; Liska, Vladimir; Schödel, Florian P; Bhuyan, Prakash K

2012-02-14

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority. Copyright © 2012 Elsevier Ltd. All rights reserved.

An In-home Advanced Robotic System to Manage Elderly Home-care Patients' Medications: A Pilot Safety and Usability Study.

PubMed

Rantanen, Pekka; Parkkari, Timo; Leikola, Saija; Airaksinen, Marja; Lyles, Alan

2017-05-01

We examined the safety profile and usability of an integrated advanced robotic device and telecare system to promote medication adherence for elderly home-care patients. There were two phases. Phase I aimed to verify under controlled conditions in a single nursing home (n = 17 patients) that no robotic malfunctions would hinder the device's safe use. Phase II involved home-care patients from 3 sites (n = 27) who were on long-term medication. On-time dispensing and missed doses were recorded by the robotic system. Patients' and nurses' experiences were assessed with structured interviews. The 17 nursing home patients had 457 total days using the device (Phase I; mean, 26.9 per patient). On-time sachet retrieval occurred with 97.7% of the alerts, and no medication doses were missed. At baseline, Phase II home-dwelling patients reported difficulty remembering to take their medicines (23%), and 18% missed at least 2 doses per week. Most Phase II patients (78%) lived alone. The device delivered and patients retrieved medicine sachets for 99% of the alerts. All patients and 96% of nurses reported the device was easy to use. This trial demonstrated the safety profile and usability of an in-home advanced robotic device and telecare system and its acceptability to patients and nurses. It supports individualized patient dosing schedules, patient-provider communications, and on-time, in-home medication delivery to promote adherence. Real time dose-by-dose monitoring and communication with providers if a dose is missed provide oversight generally not seen in home care. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open, Controlled Study.

PubMed

Sirima, Sodiomon B; Tiono, Alfred; Gansané, Zakaria; Siribié, Mohamadou; Zongo, Angèle; Ouédraogo, Alphonse; François, Nancy; Strezova, Ana; Dobbelaere, Kurt; Borys, Dorota

2017-05-01

Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in children with sickle cell disease (SCD), who are at increased risk for infections. In this phase III, open-label, single-center, controlled study in Burkina Faso (NCT01175083), children with SCD (S) or without SCD (NS) were assigned to 6 groups (N = 300): children 8-11 weeks of age (<6 months; <6S and <6NS groups) received 3 primary doses and a booster dose of PHiD-CV coadministered with routine childhood vaccines; children 7-11 months of age (7-11S and 7-11NS groups) received 2 primary doses and a booster dose of PHiD-CV; children 12-23 months of age (12-23S and 12-23NS groups) received 2 catch-up doses of PHiD-CV. Pneumococcal antibody responses were measured using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity. Responses to other antigens were measured by enzyme-linked immunosorbent assay. Adverse events were recorded. One month postprimary vaccination, for each vaccine serotype ≥98% of infants in the <6S and <6NS groups had antibody concentrations ≥0.2 µg/mL, except for 6B (≥85%) and 23F (≥89%). Immune responses to PHiD-CV after age-appropriate vaccination in children <2 years did not appear influenced by SCD. All infants were seroprotected/seropositive for diphtheria, tetanus and Bordetella pertussis antigens postprimary and booster vaccination. Safety and reactogenicity profiles were similar in children with or without SCD. PHiD-CV was immunogenic with an acceptable safety profile in children with and without SCD starting vaccination at 8 weeks to 23 months of age.

Feasibility and acceptability of interventions to delay gun access in VA mental health settings.

PubMed

Walters, Heather; Kulkarni, Madhur; Forman, Jane; Roeder, Kathryn; Travis, Jamie; Valenstein, Marcia

2012-01-01

The majority of VA patient suicides are completed with firearms. Interventions that delay patients' gun access during high-risk periods may reduce suicide, but may not be acceptable to VA stakeholders or may be challenging to implement. Using qualitative methods, stakeholders' perceptions about gun safety and interventions to delay gun access during high-risk periods were explored. Ten focus groups and four individual interviews were conducted with key stakeholders, including VA mental health patients, mental health clinicians, family members and VA facility leaders (N=60). Transcripts were consensus-coded by two independent coders, and structured summaries were developed and reviewed using a consensus process. All stakeholder groups indicated that VA health system providers had a role in increasing patient safety and emphasized the need for providers to address gun access with their at-risk patients. However, VA mental health patients and clinicians reported limited discussion regarding gun access in VA mental health settings during routine care. Most, although not all, patients and clinicians indicated that routine screening for gun access was acceptable, with several noting that it was more acceptable for mental health patients. Most participants suggested that family and friends be involved in reducing gun access, but expressed concerns about potential family member safety. Participants generally found distribution of trigger locks acceptable, but were skeptical about its effectiveness. Involving Veteran Service Organizations or other individuals in temporarily holding guns during high-risk periods was acceptable to many participants but only with numerous caveats. Patients, clinicians and family members consider the VA health system to have a legitimate role in addressing gun safety. Several measures to delay gun access during high-risk periods for suicide were seen as acceptable and feasible if implemented thoughtfully. Published by Elsevier Inc.

The use of a driving simulator to determine how time pressures impact driver aggressiveness.

PubMed

Fitzpatrick, Cole D; Samuel, Siby; Knodler, Michael A

2017-11-01

Speeding greatly attributes to traffic safety with approximately a third of fatal crashes in the United States being speeding-related. Previous research has identified being late as a primary cause of speeding. In this driving simulator study, a virtual drive was constructed to evaluate how time pressures, or hurried driving, affected driver speed choice and driver behavior. In particular, acceleration profiles, gap acceptance, willingness to pass, and dilemma zone behavior were used, in addition to speed, as measures to evaluate whether being late increased risky and aggressive driving behaviors. Thirty-six drivers were recruited with an equal male/female split and a broad distribution of ages. Financial incentives and completion time goals calibrated from a control group were used to generate a Hurried and Very Hurried experimental group. As compared to the control group, Very Hurried drivers selected higher speeds, accelerated faster after red lights, accepted smaller gaps on left turns, were more likely to pass a slow vehicle, and were more likely to run a yellow light in a dilemma zone situation. These trends were statistically significant and were also evident with the Hurried group but a larger sample would be needed to show statistical significance. The findings from this study provide evidence that hurried drivers select higher speeds and exhibit riskier driving behaviors. These conclusive results have possible implications in areas such as transportation funding and commercial motor vehicle safety. Published by Elsevier Ltd.

76 FR 5494 - Pipeline Safety: Mechanical Fitting Failure Reporting Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-01

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration 49 CFR Part... Safety: Mechanical Fitting Failure Reporting Requirements AGENCY: Pipeline and Hazardous Materials Safety... tightening. A widely accepted industry guidance document, Gas Pipeline Technical Committee (GPTC) Guide, does...

Multidimensional Characterization of Sexual Minority Adolescents’ Sexual Safety Strategies

PubMed Central

Masters, N. Tatiana; Beadnell, Blair; Morrison, Diane M.; Hoppe, Marilyn J.; Wells, Elizabeth A.

2013-01-01

Young adults have high rates of sexually transmitted infections (STIs). Sexual minority youths’ risk for STIs, including HIV, is as high as or higher than sexual majority peers’. Sexual safety, while often treated as a single behavior such as condom use, can be best conceptualized as the result of multiple factors. We used latent class analysis to identify profiles based on ever-used sexual safety strategies and lifetime number of partners among 425 self-identified LGBTQ youth aged 14-19. Data collection took place anonymously online. We identified four specific subgroup profiles for males and three for females, with each subgroup representing a different level and type of sexual safety. Profiles differed from each other in terms of age and outness for males, and in outness, personal homonegativity, and amount of education received about sexual/romantic relationships for females. Youths’ sexual safety profiles have practice implications for sexuality educators, health care professionals, and parents. PMID:24011111

Adapting Extension Food Safety Programming for Vegetable Growers to Accommodate Differences in Ethnicity, Farming Scale, and Other Individual Factors

ERIC Educational Resources Information Center

Kline, Terence R.; Kneen, Harold; Barrett, Eric; Kleinschmidt, Andy; Doohan, Doug

2012-01-01

Differences in vegetable production methods utilized by American growers create distinct challenges for Extension personnel providing food safety training to producer groups. A program employing computers and projectors will not be accepted by an Amish group that does not accept modern technology. We have developed an outreach program that covers…

Nuclear regulation: an evaluative study. [Monograph

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

Wood, W.C.

This paper gives an overview of nuclear regulation, followed by an account of the legislative rationale and the economic rationale for safety regulation of nuclear technology. It goes on to review the structure and safety programs of the Nuclear Regulatory Commission (NRC) and to show how many of the NRC's problems are unlike those facing other regulatory agencies. In assessing the results of nuclear regulation, it examines whether regulation has produced an acceptable level of safety and the nature of the evidence on acceptability. It concludes that the existing level of safety achievement is not cost-effective, and identifies some sourcesmore » of regulatory failure as a failure to make hard decisions on risk, diffuse responsibility for safety, and economic dissincentives to cost-effective safety. Recommendations for reforming NRC are to separate technical issues from social ones and to correct the incentives for safety. 153 references, 6 figures, 4 tables.« less

Expert opinions on the acceptance of alternative methods in food safety evaluations: Formulating recommendations to increase acceptance of non-animal methods for kinetics.

PubMed

Punt, Ans; Bouwmeester, Hans; Schiffelers, Marie-Jeanne W A; Peijnenburg, Ad A C M

2018-02-01

Inclusion of alternative methods that replace, reduce, or refine (3R) animal testing within regulatory safety evaluations of chemicals generally faces many hurdles. The goal of the current work is to i) collect responses from key stakeholders involved in food safety evaluations on what they consider the most relevant factors that influence the acceptance and use of 3R methods and to ii) use these responses to formulate activities needed to increase the acceptance and use of 3R methods, particularly for kinetics. The stakeholders were contacted by e-mail for their opinions, asking the respondents to write down three barriers and/or drivers and scoring these by distributing 5 points over the three factors. The main barriers that obtained the highest aggregated scores were i) uncertain predictability 3R methods/lack of validation, ii) insufficient guidance regulators/industry and iii) insufficient harmonization of legislation. The major driver identified was the possibility of 3R methods to provide more mechanistic information. Based on the results, recommendations are given to enhance the acceptance and application of 3R toxicokinetic methods in food safety evaluations. These include steering of regulatory data requirements as well as creating (funding) opportunities for development and validation of alternative methods for kinetics and development of guidances. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Consumer acceptance of irradiated food: theory and reality

NASA Astrophysics Data System (ADS)

Bruhn, Christine M.

1998-06-01

For years most consumers have expressed less concern about food irradiation than other food processing technologies. Attitude studies have demonstrated that when given science-based information, from 60% to 90% of consumers prefer the advantages irradiation processing provides. When information is accompanied by samples, acceptance may increase to 99%. Information on irradiation should include product benefits, safety and wholesomeness, address environmental safety issues, and include endorsements by recognized health authorities. Educational and marketing programs should now be directed toward retailers and processors. Given the opportunity, consumers will buy high quality, safety-enhanced irradiated food.

Determinants of debit cards acceptance: An empirical investigation

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

Ismail, Shafinar; Adnan, Azimah; Azizi, Amsyar

These days, most of the Malaysians realize that the consumption of debit card will help them to reduce the household debt. Thus, it is important to analyse the acceptance of debit cards for further enhancement and expanding its market share in Malaysia. In addition, there is lacked of research being conducted on the determinants affecting the acceptance of debit cards among Malaysians. Thus, the study aimed to investigate the factors affecting the acceptance of debit cards. This study focuses on payment methods, consumer attitude, and safety of debit card in acceptance of debit cards. Questionnaires were distributed to the 300more » respondents. The sampling procedure adopted was stratified random sampling. The data obtained were analysed using SPSS 20.0 which involves scale reliability, descriptive and regression analysis. The result indicates that payment methods, consumer attitude and safety are the determinants of debit cards acceptance. Safety is the best predictor as most of the customers are confidents to use debit cards because of the security being developed around these debit card transactions. The analyses presented in this study can be used by policymakers and managers as a guide to promote banking products and services. The findings achieved in this study will be of interest for practitioners and academics concerned with developments of the Malaysian banking industry.« less

Determinants of debit cards acceptance: An empirical investigation

NASA Astrophysics Data System (ADS)

Ismail, Shafinar; Bakri, Mohamed Hariri; Zulkepli, Jafri; Adnan, Azimah; Azizi, Amsyar

2014-12-01

These days, most of the Malaysians realize that the consumption of debit card will help them to reduce the household debt. Thus, it is important to analyse the acceptance of debit cards for further enhancement and expanding its market share in Malaysia. In addition, there is lacked of research being conducted on the determinants affecting the acceptance of debit cards among Malaysians. Thus, the study aimed to investigate the factors affecting the acceptance of debit cards. This study focuses on payment methods, consumer attitude, and safety of debit card in acceptance of debit cards. Questionnaires were distributed to the 300 respondents. The sampling procedure adopted was stratified random sampling. The data obtained were analysed using SPSS 20.0 which involves scale reliability, descriptive and regression analysis. The result indicates that payment methods, consumer attitude and safety are the determinants of debit cards acceptance. Safety is the best predictor as most of the customers are confidents to use debit cards because of the security being developed around these debit card transactions. The analyses presented in this study can be used by policymakers and managers as a guide to promote banking products and services. The findings achieved in this study will be of interest for practitioners and academics concerned with developments of the Malaysian banking industry.

Of Acceptable Risk: Science and the Determination of Safety.

ERIC Educational Resources Information Center

Lowrance, William W.

This book looks at the problems of determination of safety and the underlying concept of safety itself. It is believed that if certain pervasive themes are properly appreciated, the whole field of safety will be better understood. The first chapter of the book sketches the general nature of safety decisions, defining safety as a measure of the…

Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme

PubMed Central

Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

2014-01-01

Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and adult women. PMID:24644063

49 CFR 212.213 - Motive power and equipment (MP&E) inspector.

Code of Federal Regulations, 2014 CFR

2014-10-01

... of determining compliance with all sections of the Freight Car Safety Standards (49 CFR part 215... maintenance standards accepted in the industry; and (ii) The Freight Car Safety Standards, Safety Glazing... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State...

49 CFR 212.213 - Motive power and equipment (MP&E) inspector.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of determining compliance with all sections of the Freight Car Safety Standards (49 CFR part 215... maintenance standards accepted in the industry; and (ii) The Freight Car Safety Standards, Safety Glazing... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State...

49 CFR 212.213 - Motive power and equipment (MP&E) inspector.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of determining compliance with all sections of the Freight Car Safety Standards (49 CFR part 215... maintenance standards accepted in the industry; and (ii) The Freight Car Safety Standards, Safety Glazing... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State...

49 CFR 212.213 - Motive power and equipment (MP&E) inspector.

Code of Federal Regulations, 2013 CFR

2013-10-01

... of determining compliance with all sections of the Freight Car Safety Standards (49 CFR part 215... maintenance standards accepted in the industry; and (ii) The Freight Car Safety Standards, Safety Glazing... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State...

In the Shadow of the Arch: Safety and Acceptance of Lesbian, Gay, Bisexual, Transgender and Queer Students at the University of Georgia.

ERIC Educational Resources Information Center

Hill, Robert J.; Childers, JoEllen; Childs, Adrian P.; Cowie, Gail; Hatton, Annette; Lewis, Jamie B.; MacNair, Nancy; Oswalt, Sara; Perez, Ruperto M.; Valentine, Thomas

The Campus Climate Research Group at the University of Georgia conducted a survey to explore safety and acceptance issues for lesbian, gay, transgender, and queer (LGBTQ) students at the university. The findings are based on 82 questionnaires returned form 223 surveys distributed to the LGBTQ community in fall 2001. The research results indicate…

47 CFR 87.39 - Equipment acceptable for licensing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Equipment acceptable for licensing. 87.39 Section 87.39 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Applications and Licenses § 87.39 Equipment acceptable for licensing...

47 CFR 87.39 - Equipment acceptable for licensing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Equipment acceptable for licensing. 87.39 Section 87.39 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Applications and Licenses § 87.39 Equipment acceptable for licensing...

Safety in Outdoor Adventure Programs. S.O.A.P. Safety Policy.

ERIC Educational Resources Information Center

MacDonald, Wayne, Comp.; And Others

Drafted in 1978 as a working document for Safety in Outdoor Adventure Programs (S.O.A.P.) by a council of outdoor adventure programmers, checklists outline standard accepted safety policy for Outdoor Adventure Programs and Wilderness Adventure Programs conducted through public or private agencies in California. Safety policy emphasizes: the…

Safety, Tolerability, and Antihypertensive Effect of SER100, an Opiate Receptor-Like 1 (ORL-1) Partial Agonist, in Patients With Isolated Systolic Hypertension.

PubMed

Kantola, Ilkka; Scheinin, Mika; Gulbrandsen, Trygve; Meland, Nils; Smerud, Knut T

2017-11-01

The purpose of the present trial was to evaluate safety, tolerability, and effect on systolic blood pressure (SBP) of SER100 in a small group of patients with isolated systolic hypertension (ISH) in treatment with at least 1 antihypertensive drug. Eligible patients were randomized to either SER100 (10 mg) or placebo in a crossover design, and 2 doses were given subcutaneously (SC), 8 hours apart, on 2 consecutive days. On all treatment days patients were monitored with an ambulatory blood pressure measurement device for 12 daytime hours. Seventeen patients completed treatment. There were no serious or severe adverse events. Relative to placebo SER100 induced an average reduction of SBP during the 2 treatment days of 7.0 mm Hg (P = 0.0032), whereas the average reduction of diastolic blood pressure (DBP) over the same period was 3.8 mm Hg (P = 0.0011). For patients with ISH, this short-term cross-over study of SC SER100 demonstrated an acceptable safety profile and consistent, significant lowering of SBP and DBP. As initial clinical proof of concept for a new class of drugs, a nociceptin agonist peptide, the results were encouraging and warrant further research. © 2016, The American College of Clinical Pharmacology.

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

PubMed

Diamond, Michael P; Carr, Bruce; Dmowski, W Paul; Koltun, William; O'Brien, Chris; Jiang, Ping; Burke, Joshua; Jimenez, Roland; Garner, Elizabeth; Chwalisz, Kristof

2014-03-01

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

Nutritional agents with anti-inflammatory properties in chemoprevention of colorectal neoplasia.

PubMed

Hull, Mark A

2013-01-01

The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer (CRC). Several naturally occurring substances with anti-inflammatory properties, used in a purified 'nutraceutical' form, including omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and polyphenols such as curcumin and resveratrol, have been demonstrated to have anti-CRC activity in preclinical models. As expected, these agents have an excellent safety and tolerability profile in Phase II clinical trials. Phase III randomized clinical trials of these naturally occurring substances are now beginning to be reported. The omega-3 polyunsaturated fatty acid EPA, in the free fatty acid (FFA) form, has been demonstrated to reduce adenomatous polyp number and size in patients with familial adenomatous polyposis (FAP), a finding which has prompted evaluation of this formulation of EPA for prevention of 'sporadic' colorectal neoplasia. Anti-inflammatory 'nutraceuticals' require further clinical evaluation in polyp prevention trials as they exhibit many of the characteristics of the ideal cancer chemoprevention agent, including safety, tolerability and patient acceptability.

Assessing children's perceptions of academic interventions: The Kids Intervention Profile.

PubMed

Eckert, Tanya L; Hier, Bridget O; Hamsho, Narmene F; Malandrino, Rigby D

2017-06-01

The psychometric properties of the Kids Intervention Profile (KIP), a rating scale designed to measure academic intervention acceptability from the perspective of students, were examined as well as the influence of background factors on students' acceptability ratings. Data were extracted from 4 randomized controlled trials investigating the effects of a performance feedback intervention on third-grade students' writing fluency (n = 228). Results indicated that the KIP contains 2 factors (General Intervention Acceptability, Skill Improvement) and has adequate internal consistency and stability across a 3-week period. There were gender differences in students' acceptability ratings, with female students rating the intervention as significantly more acceptable than males. In addition, results suggested a modest, positive relationship between students' intervention acceptability ratings and their intervention outcomes. Considerations regarding the use of the KIP, as well as limitations of the study, are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Public acceptability of highway safety countermeasures. Volume 1, Background of study and methodology

DOT National Transportation Integrated Search

1981-06-01

This study provides information about public attitudes towards proposed highway safety countermeasures in three program areas: alcohol and drugs, unsafe driving behaviors, and pedestrian safety. This volume describes the three research methodologies ...

Comparative safety and efficacy of subcutaneous and intradermal administration of inactivated Japanese encephalitis vaccine during predeployment preparations in the Australian Defence Force.

PubMed

Kitchener, Scott; Nasveld, Peter; Brennan, Len; Ward, David

2006-12-01

Japanese encephalitis is a viral disease emerging in areas of influence for the Australian Defence Force immediately north of the continent, including the Torres Strait border of Australia and Papua, New Guinea. Only the mouse brain-derived, inactivated, Nakayama strain vaccine is commercially available to the Australian Defence Force. This vaccine has a high cost and significant adverse event profile, requiring restricted duties after administration. To address these issues, intradermal vaccination (either single intradermal administration or two intradermal injections at two separate sites) was assessed, compared with the conventional subcutaneous vaccination method, in a randomized controlled trial among soldiers preparing for deployment. Dual intradermal vaccination (0.1 mL at two sites) was found to have a slightly more favorable adverse event profile while maintaining comparable serological efficacy and reduced cost. An expansion of the concept and a test of logistics were conducted by vaccinating a battalion formation during predeployment medical preparations. The method of vaccination was well accepted and retained comparable immunogenicity.

Radiation fields from neutron generators shielded with different materials

NASA Astrophysics Data System (ADS)

Chichester, D. L.; Blackburn, B. W.

2007-08-01

As a general guide for assessing radiological conditions around a DT neutron generator numerical modeling has been performed to assess neutron and photon dose profiles for a variety of shield materials ranging from 1 to 100 cm thick. In agreement with accepted radiation safety practices high-Z materials such as bismuth and lead have been found to be ineffective biological shield materials, owing in part to the existence of (n,2n) reaction channels available with 14.1 MeV DT neutrons, while low-Z materials serve as effective shields for these sources. Composite materials such as a mixture of polyethylene and bismuth, or regular concrete, are ideal shield materials for neutron generator radiation because of their ability to attenuate internally generated photon radiation resulting from neutron scattering and capture within the shields themselves.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

PubMed

Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

2017-09-01

Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Longitudinal Stability of Social Competence Indicators in a Portuguese Sample: Q-Sort Profiles of Social Competence, Measures of Social Engagement, and Peer Sociometric Acceptance

ERIC Educational Resources Information Center

Santos, António J.; Vaughn, Brian E.; Peceguina, Inês; Daniel, João R.

2014-01-01

This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple…

Factor Structure and Reliability of the Dutch Version of Seven Scales of the Communication Profile for the Hearing Impaired (CPHI)

ERIC Educational Resources Information Center

Mokkink, Lidwine B.; Knol, Dirk L.; Zekveld, Adriana A.; Goverts, S. Theo; Kramer, Sophia E.

2009-01-01

Purpose: Seven scales of the Communication Profile for the Hearing Impaired (CPHI; M. E. Demorest & S. A. Erdman, 1987) were translated into Dutch: Maladaptive Behavior, Verbal Strategies, and Nonverbal Strategies (within the area of Communication Strategies) and Self-Acceptance, Acceptance of Loss, Stress, and Withdrawal (within the area of…

Modified Atkins diet vs classic ketogenic formula in intractable epilepsy.

PubMed

El-Rashidy, O F; Nassar, M F; Abdel-Hamid, I A; Shatla, R H; Abdel-Hamid, M H; Gabr, S S; Mohamed, S G; El-Sayed, W S; Shaaban, S Y

2013-12-01

The study was designed to evaluate the efficacy, safety, and tolerability of the ketogenic diet (KD) whether classic 4:1 formula or the modified Atkins diet (MAD) in intractable childhood epilepsy. Anthropometric measurements and serum lipid profile were measured upon enrollment and after 3 and 6 months in 40 patients with symptomatic intractable epilepsy. Fifteen were given MAD diet, ten were kept on classic 4:1 ketogenic liquid formula, and the rest were allowed to eat as desired. The liquid ketogenic formula group showed significantly higher body mass index compared with those who did not receive KD after 6 months. The lipid profile of KD patients was within normal limits for age and sex during the study period. The rate of change of frequency and severity of seizures showed best improvement in ketogenic liquid formula patients followed by the MAD group than the patients on anti-epileptic medications alone. The KD whether classic 4:1 or MAD is a tolerable, safe, and effective adjuvant therapy for intractable symptomatic childhood epilepsy with limited adverse effects on the growth parameters and accepted changes in the lipid profile. The liquid ketogenic formula patients showed better growth pattern and significantly more seizure control. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer

PubMed Central

Costa, Rubens Barros; Costa, Ricardo L.B.; Talamantes, Sarah M.; Kaplan, Jason B.; Bhave, Manali A.; Rademaker, Alfred; Miller, Corinne; Carneiro, Benedito A.; Mahalingam, Devalingam; Chae, Young Kwang

2018-01-01

Introduction Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Materials and Methods A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. Results Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. Conclusions ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs. PMID:29774128

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.

Sensory Profile and Consumer Acceptability of Prebiotic White Chocolate with Sucrose Substitutes and the Addition of Goji Berry (Lycium barbarum).

PubMed

Morais Ferreira, Janaína Madruga; Azevedo, Bruna Marcacini; Luccas, Valdecir; Bolini, Helena Maria André

2017-03-01

Functional food is a product containing nutrients that provide health benefits beyond basic nutrition. The objective of the present study was to evaluate the descriptive sensory profile and consumers' acceptance of functional (prebiotic) white chocolates with and without the addition of an antioxidant source (goji berry [GB]) and sucrose replacement. The descriptive sensory profile was determined by quantitative descriptive analysis (QDA) with trained assessors (n = 12), and the acceptance test was performed with 120 consumers. The correlation of descriptive and hedonic data was determined by partial least squares (PLS). The results of QDA indicated that GB reduces the perception of most aroma and flavor attributes, and enhances the bitter taste, bitter aftertaste, astringency, and most of the texture attributes. The consumers' acceptance of the chocolates was positive for all sensory characteristics, with acceptance scores above 6 on a 9-point scale. According to the PLS regression analysis, the descriptors cream color and cocoa butter flavor contributed positively to the acceptance of functional white chocolates. Therefore, prebiotic white chocolate with or without the addition of GB is innovative and can attract consumers, due to its functional properties, being a promising alternative for the food industry. © 2017 Institute of Food Technologists®.

The attitude of Canadian university students toward a behavior-based blood donor health assessment questionnaire.

PubMed

Go, Stephanie L; Lam, Cindy T Y; Lin, Yahui T; Wong, Deborah J; Lazo-Langner, Alejandro; Chin-Yee, Ian

2011-04-01

In Canada, all men who have sex with men (MSM) are indefinitely deferred from donating blood. The purpose of this study was to determine the acceptability of an alternative behavior-based donor health questionnaire among Canadian university students. Further we sought to determine the perception of blood safety associated with specific risk behaviors. Questions found on the Canadian Blood Services' donor health assessment questionnaire as well as from studies assessing high-risk behavior for human immunodeficiency virus infection were included. For each question participants were asked to rate the acceptability, comfort in answering, perceived effect on blood safety, and whether the question would deter them from donating blood. Data were analyzed using nonparametric tests. A total of 741 students participated in the study. Questions regarding sexual practices of the donor were rated less important for blood safety compared to those assessing for sexually transmitted infections, sex for money, and injection drug use (30%-62% vs. 69%-95% unsafe). A total of 24.4% of students rated both questions on MSM status and a behavior-based alternative as equally unacceptable. We found an inverse correlation between perception of safety and acceptability of questions. Our findings suggest that a behavior-based screening modification is unlikely to change opinions or satisfy those who object to the MSM current policy in place. Acceptability of these questions might be related to a poor understanding of the effect of sexual practices on blood supply safety. © 2010 American Association of Blood Banks.

Public acceptability of highway safety countermeasures. Volume 3, Alcohol and drug research

DOT National Transportation Integrated Search

1981-06-01

This volume, part of a larger study on public attitudes towards proposed highway safety countermeasures for alcohol and drugs, unsafe driving behaviors, and pedestrian safety, discusses reactions to breath testers, drunk-driving deterrence techniques...

Energy-restricted, high-protein diets more effectively impact cardiometabolic profile in overweight and obese women than lower-protein diets.

PubMed

Mateo-Gallego, Rocío; Marco-Benedí, Victoria; Perez-Calahorra, Sofía; Bea, Ana M; Baila-Rueda, Lucía; Lamiquiz-Moneo, Itziar; de Castro-Orós, Isabel; Cenarro, Ana; Civeira, Fernando

2017-04-01

High-protein energy-restricted diets have demonstrated efficacy in promoting weight loss in overweight and obesity. However, the protein percentage that achieves optimal efficacy and acceptability remains unknown. We sought to assess the effects of three energy-reduced diets with different percentages of calories from protein (20%, 27%, and 35%) on weight loss and lipids. Secondary outcomes included diet acceptability and compliance. Six-month, randomized study included women aged 18-80 years with BMI of 27.5-45 kg/m 2 and who were not taking lipid-lowering drugs. We randomly assigned 91 women to one of three calorie-reduced diets with: protein, 20%, 27%, or 35% (80% from animal protein); carbohydrates, 50%, 43%, or 35%; fat, 30%. Dietary intervention involved individual visits with a nutritionist every 2 weeks during the first 3 months. We performed a follow-up visit at 6 months. Eighty women aged 44.0 ± 9.08 years with BMI of 37.7 ± 3.39 kg/m 2 completed the study. At 3 months, weight loss was -8.16 ± 4.18 kg, -9.66 ± 5.28 kg, and -10.7 ± 4.28 kg in the 20%, 27%, and 35%-protein groups, respectively (P = 0.16). These figures slightly and homogeneously increased at 6 months. Around 65% of women following 35%-protein diet lost ≥10% of body weight vs. ∼33% in 20%-protein group (P = 0.023). Significant decreases occurred in fat mass, lipids and insulin resistance, especially in the 35%-protein group (P < 0.05 vs. 20% protein). This improvement was not fully explained by weight loss. Triglyceride change was negatively correlated with animal-protein intake. All groups provided similar responses to an acceptance, palatability, and satisfaction questionnaire. An energy-restricted diet with 35% protein, mostly of animal origin, more effectively impacts cardiometabolic profile than an energy-restricted diet with lower protein content although no clear benefit between diets in terms of overall weight loss was observed. The high-protein diet displayed an excellent safety profile and acceptability. This trial was registered in ClinicalTrials.gov as NCT02160496. The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02160496). Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Pilot Study of an Active Screen Time Game Correlates with Improved Physical Fitness in Minority Elementary School Youth.

PubMed

Bethea, Terrence C; Berry, Diane; Maloney, Ann E; Sikich, Linmarie

2012-02-01

The aim of our feasibility study was to examine the acceptability and utility of "Dance Dance Revolution" (DDR) (Konami of America, Redwood City, CA)) to increase physical fitness in 8-11-year-old black and Hispanic youth. Twenty-eight 4(th) and 5(th) grade children attending an afterschool program participated. Outcomes included physical activity, physical fitness, use of home DDR, survey of safety and acceptability, anthropometrics, and fasting metabolic profile measured at baseline, 12 weeks, and 30 weeks. At 12 weeks, physical fitness (maximum O2 uptake [VO2max]) increased by 4.9±9.9 percent and was sustained through 30 weeks, when the VO2max was 105.0±9.9 percent (range, 93.0-133.9 percent) of baseline values. Absolute VO2max increased by 2.97±4.99 mL/kg/minute (95% confidence interval 0.75-5.19, P=0.013). Participants maintained an average of 1.12 hours/day of increased movement to music. Trends suggested increased total moderate-vigorous physical activity, decreased light activity, and a modest increase in sedentary screen time. There were no significant changes in body mass index, fasting lipids, or glucose. Participants and parents approved of the activity. DDR appears feasible and acceptable to minority youth. DDR may increase moderate-vigorous physical activity and improve physical fitness in at-risk populations.

Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial.

PubMed

Younes, Anas; Santoro, Armando; Shipp, Margaret; Zinzani, Pier Luigi; Timmerman, John M; Ansell, Stephen; Armand, Philippe; Fanale, Michelle; Ratanatharathorn, Voravit; Kuruvilla, John; Cohen, Jonathon B; Collins, Graham; Savage, Kerry J; Trneny, Marek; Kato, Kazunobu; Farsaci, Benedetto; Parker, Susan M; Rodig, Scott; Roemer, Margaretha G M; Ligon, Azra H; Engert, Andreas

2016-09-01

Malignant cells of classical Hodgkin's lymphoma are characterised by genetic alterations at the 9p24.1 locus, leading to overexpression of PD-1 ligands and evasion of immune surveillance. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed and refractory classical Hodgkin's lymphoma, with an acceptable safety profile. We aimed to assess the clinical benefit and safety of nivolumab monotherapy in patients with classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin. In this ongoing, single-arm phase 2 study, adult patients (aged ≥18 years) with recurrent classical Hodgkin's lymphoma who had failed to respond to autologous stem-cell transplantation and had either relapsed after or failed to respond to brentuximab vedotin, and with an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled from 34 hospitals and academic centres across Europe and North America. Patients were given nivolumab intravenously over 60 min at 3 mg/kg every 2 weeks until progression, death, unacceptable toxicity, or withdrawal from study. The primary endpoint was objective response following a prespecified minimum follow-up period of 6 months, assessed by an independent radiological review committee (IRRC). All patients who received at least one dose of nivolumab were included in the primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02181738. Among 80 treated patients recruited between Aug 26, 2014, and Feb 20, 2015, the median number of previous therapies was four (IQR 4-7). At a median follow-up of 8·9 months (IQR 7·8-9·9), 53 (66·3%, 95% CI 54·8-76·4) of 80 patients achieved an IRRC-assessed objective response. The most common drug-related adverse events (those that occurred in ≥15% of patients) included fatigue (20 [25%] patients), infusion-related reaction (16 [20%]), and rash (13 [16%]). The most common drug-related grade 3 or 4 adverse events were neutropenia (four [5%] patients) and increased lipase concentrations (four [5%]). The most common serious adverse event (any grade) was pyrexia (three [4%] patients). Three patients died during the study; none of these deaths were judged to be treatment related. Nivolumab resulted in frequent responses with an acceptable safety profile in patients with classical Hodgkin's lymphoma who progressed after autologous stem-cell transplantation and brentuximab vedotin. Therefore, nivolumab might be a new treatment option for a patient population with a high unmet need. Ongoing follow-up will help to assess the durability of response. Bristol-Myers Squibb. Copyright © 2016 Elsevier Ltd. All rights reserved.

Social Acceptance of Wind: A Brief Overview (Presentation)

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

Lantz, E.

This presentation discusses concepts and trends in social acceptance of wind energy, profiles recent research findings, and discussions mitigation strategies intended to resolve wind power social acceptance challenges as informed by published research and the experiences of individuals participating in the International Energy Agencies Working Group on Social Acceptance of Wind Energy

Clinical evaluation of a dressing with poly absorbent fibres and a silver matrix for managing chronic wounds at risk of infection: a non comparative trial.

PubMed

Dalac, S; Sigal, L; Addala, A; Chahim, M; Faivre-Carrere, C; Lemdjadi, Z; Bohbot, S

2016-09-01

To assess the efficacy, safety and acceptability of a new silver poly absorbent dressing (UrgoCleanAg) in the local management of exudative chronic wounds at risk of infection, with inflammatory signs suggesting heavy bacterial load. This prospective, multicentre, non-comparative clinical trial was conducted in French hospital wards (dermatology and vascular medicine) or specialised private-practice physicians. Patients were considered at high-risk of infection when presenting with at least three of five selected inflammatory clinical signs, suggesting a heavy bacterial load (pain between two dressing changes, erythema, oedema, malodorous wound and presence of a heavy exudate). They were treated for a maximum period of four weeks, and followed by the physician on a weekly basis, including a clinical examination, area tracings and photographs. The primary efficacy criterion of the trial was the relative wound surface area reduction at the end of the four weeks of treatment. Acceptability was documented by the nursing staff at each dressing change between the weekly evaluations. We recruited 37 patients with chronic wounds. Wound surface area, mostly covered by sloughy tissue, was reduced by 32.5% at the end of the treatment (median value), while the clinical score (maximum value of 5, based on inflammatory clinical signs) decreased from 4.0 to 2.0. Effective debridement properties were documented (62.5% relative reduction of sloughy tissue at week 4; 58.8% of debrided wounds at week 4) and improvement of the periwound skin status was noted (healthy for 28.6% of the patients at week 4 versus 2.7% at baseline). In addition, the tested wound dressing presented a good safety profile associated to a high level of acceptability, noted by both patients and nursing staff. These clinical data support that the tested dressing is a credible therapeutic alternative for the management of chronic wounds at risk of infection with inflammatory signs suggesting heavy bacterial load.

Influence of facial convexity on facial attractiveness in Japanese.

PubMed

Ioi, H; Nakata, S; Nakasima, A; Counts, Al

2007-11-01

The purpose of this study was to assess and determine the range of the top three most-favored facial profiles for each sex from a series of varying facial convexity, and to evaluate the clinically acceptable facial profiles for Japanese adults. Questionnaire-based study. Silhouettes of average male and female profiles were constructed from the profiles of 30 Japanese males and females with normal occlusions. Chin positions were protruded or retruded by 2 degrees , 4 degrees , 6 degrees , 8 degrees and 10 degrees , respectively, from the average profile. Forty-one orthodontists and 50 dental students were asked to select the three most-favored profiles for each sex, and they were also asked to indicate whether they would seek surgical orthodontic treatment if that image represented their own profile. For males, both the orthodontists and dental students chose the average profile as the most-favored profile. For females, both the orthodontists and dental students chose a slightly more retruded chin position as the most-favored profile. Japanese raters tended to choose class II profiles as more acceptable profiles than class III profiles for both males and females. These findings suggest that Japanese patients with class III profiles tend to seek surgical orthodontic treatment more often.

Public acceptability of highway safety countermeasures. Volume 2, Safe driving conformance research

DOT National Transportation Integrated Search

1981-06-01

This volume is part of a larger study providing information about public attitudes towards proposed highway safety countermeasures in three program areas: alcohol and drugs, unsafe driving behaviors, and pedestrian safety. Topic areas discussed in th...

Participation of low-income women in genetic cancer risk assessment and BRCA 1/2 testing: the experience of a safety-net institution.

PubMed

Komenaka, Ian K; Nodora, Jesse N; Madlensky, Lisa; Winton, Lisa M; Heberer, Meredith A; Schwab, Richard B; Weitzel, Jeffrey N; Martinez, Maria Elena

2016-07-01

Some communities and populations lack access to genetic cancer risk assessment (GCRA) and testing. This is particularly evident in safety-net institutions, which serve a large segment of low-income, uninsured individuals. We describe the experience of a safety-net clinic with limited resources in providing GCRA and BRCA1/2 testing. We compared the proportion and characteristics of high-risk women who were offered and underwent GCRA and genetic testing. We also provide a description of the mutation profile for affected women. All 125 patients who were offered GCRA accepted to undergo GCRA. Of these, 72 % had a breast cancer diagnosis, 70 % were Hispanic, 52.8 % were non-English speakers, and 66 % did not have health insurance. Eighty four (67 %) were offered genetic testing and 81 (96 %) agreed. Hispanic women, those with no medical insurance, and those with a family history of breast cancer were significantly more likely to undergo testing (p > 0.01). Twelve of 81 (15 %) patients were found to have deleterious mutations, seven BRCA1, and five BRCA2. Our experience shows that it is possible to offer GCRA and genetic testing even in the setting of limited resources for these services. This is important given that a large majority of the low-income women in our study agreed to undergo counseling and testing. Our experience could serve as a model for similar low-resource safety-net health settings.

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

Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.

PubMed

Mullick, Adam E; Yeh, Steve T; Graham, Mark J; Engelhardt, Jeffery A; Prakash, Thazha P; Crooke, Rosanne M

2017-09-01

Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade. © 2017 American Heart Association, Inc.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

PubMed

Beköz, H; Karadurmus, N; Paydas, S; Türker, A; Toptas, T; Firatli Tuglular, T; Sönmez, M; Gülbas, Z; Tekgündüz, E; Kaya, A H; Özbalak, M; Tastemir, N; Kaynar, L; Yildirim, R; Karadogan, I; Arat, M; Pepedil Tanrikulu, F; Özkocaman, V; Abali, H; Turgut, M; Kurt Yüksel, M; Özcan, M; Dogu, M H; Kabukçu Hacioglu, S; Barista, I; Demirkaya, M; Köseoglu, F D; Toprak, S K; Yilmaz, M; Demirkürek, H C; Demirkol, O; Ferhanoglu, B

2017-10-01

Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

77 FR 45282 - NRC Position on the Relationship Between General Design Criteria and Technical Specification...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

..., are described in the final safety analysis report (FSAR). The staff safety evaluation documents the acceptability of these analyses, and it is the combination of the FSAR analyses and the staff safety evaluation... analysis, maintain their capability to perform their safety functions. Technical Specification Operability...

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

PubMed

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial

PubMed Central

Nel, Annaléne; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Background Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. Objectives This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. Methods 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. Results No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. Conclusions The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides. PMID:29813074

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...

40 CFR 68.48 - Safety information.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.48 Safety information. (a) The... generally accepted good engineering practices. Compliance with Federal or state regulations that address...

40 CFR 68.48 - Safety information.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.48 Safety information. (a) The... generally accepted good engineering practices. Compliance with Federal or state regulations that address...

40 CFR 68.48 - Safety information.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.48 Safety information. (a) The... generally accepted good engineering practices. Compliance with Federal or state regulations that address...

40 CFR 68.48 - Safety information.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.48 Safety information. (a) The... generally accepted good engineering practices. Compliance with Federal or state regulations that address...

46 CFR 28.275 - Acceptance criteria for instructors and course curricula.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Acceptance criteria for instructors and course curricula... the Aleutian Trade § 28.275 Acceptance criteria for instructors and course curricula. (a) A Fishing Vessel Safety Instructor shall submit a detailed course curriculum that relates directly to the...

46 CFR 28.275 - Acceptance criteria for instructors and course curricula.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Acceptance criteria for instructors and course curricula... the Aleutian Trade § 28.275 Acceptance criteria for instructors and course curricula. (a) A Fishing Vessel Safety Instructor shall submit a detailed course curriculum that relates directly to the...

33 CFR 175.130 - Visual distress signals accepted.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Visual distress signals accepted... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.130 Visual distress signals accepted. (a) Any of the following signals, when carried in the number required, can be used to meet the...

33 CFR 175.130 - Visual distress signals accepted.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Visual distress signals accepted... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.130 Visual distress signals accepted. (a) Any of the following signals, when carried in the number required, can be used to meet the...

33 CFR 175.130 - Visual distress signals accepted.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Visual distress signals accepted... (CONTINUED) BOATING SAFETY EQUIPMENT REQUIREMENTS Visual Distress Signals § 175.130 Visual distress signals accepted. (a) Any of the following signals, when carried in the number required, can be used to meet the...

A cloud medication safety support system using QR code and Web services for elderly outpatients.

PubMed

Tseng, Ming-Hseng; Wu, Hui-Ching

2014-01-01

Drug is an important part of disease treatment, but medication errors happen frequently and have significant clinical and financial consequences. The prevalence of prescription medication use among the ambulatory adult population increases with advancing age. Because of the global aging society, outpatients need to improve medication safety more than inpatients. The elderly with multiple chronic conditions face the complex task of medication management. To reduce the medication errors for the elder outpatients with chronic diseases, a cloud medication safety supporting system is designed, demonstrated and evaluated. The proposed system is composed of a three-tier architecture: the front-end tier, the mobile tier and the cloud tier. The mobile tier will host the personalized medication safety supporting application on Android platforms that provides some primary functions including reminders for medication, assistance with pill-dispensing, recording of medications, position of medications and notices of forgotten medications for elderly outpatients. Finally, the hybrid technology acceptance model is employed to understand the intention and satisfaction level of the potential users to use this mobile medication safety support application system. The result of the system acceptance testing indicates that this developed system, implementing patient-centered services, is highly accepted by the elderly. This proposed M-health system could assist elderly outpatients' homecare in preventing medication errors and improving their medication safety.

Drivers' safety needs, behavioural adaptations and acceptance of new driving support systems.

PubMed

Saad, Farida; Van Elslande, Pierre

2012-01-01

The aim of this paper is to discuss the contribution of two complementary approaches for designing and evaluating new driver support systems likely to improve the operation and safety of the road traffic system. The first approach is based on detailed analyses of traffic crashes so as to estimate drivers' needs for assistance and the situational constraints that safety functions should address to be efficient. The second approach is based on in depth-analyses of behavioral adaptations induced by the usage of new driver support systems in regular driving situations and on drivers' acceptance of the assistance provided by the systems.

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.

Facts about Mumps for Adults

MedlinePlus

... containing vaccine or have other acceptable evidence of immunity to the disease. College and university students, healthcare ... MMR vaccine or have other acceptable evidence of immunity to ensure adequate protection. Vaccine safety The MMR ...

The affective profiles, psychological well-being, and harmony: environmental mastery and self-acceptance predict the sense of a harmonious life

PubMed Central

Al Nima, Ali; Kjell, Oscar N.E.

2014-01-01

Background. An important outcome from the debate on whether wellness equals happiness, is the need of research focusing on how psychological well-being might influence humans’ ability to adapt to the changing environment and live in harmony. To get a detailed picture of the influence of positive and negative affect, the current study employed the affective profiles model in which individuals are categorised into groups based on either high positive and low negative affect (self-fulfilling); high positive and high negative affect (high affective); low positive and low negative affect (low affective); and high negative and low positive affect (self-destructive). The aims were to (1) investigate differences between affective profiles in psychological well-being and harmony and (2) how psychological well-being and its dimensions relate to harmony within the four affective profiles. Method. 500 participants (mean age = 34.14 years, SD. = ±12.75 years; 187 males and 313 females) were recruited online and required to answer three self-report measures: The Positive Affect and Negative Affect Schedule; The Scales of Psychological Well-Being (short version) and The Harmony in Life Scale. We conducted a Multivariate Analysis of Variance where the affective profiles and gender were the independent factors and psychological well-being composite score, its six dimensions as well as the harmony in life score were the dependent factors. In addition, we conducted four multi-group (i.e., the four affective profiles) moderation analyses with the psychological well-being dimensions as predictors and harmony in life as the dependent variables. Results. Individuals categorised as self-fulfilling, as compared to the other profiles, tended to score higher on the psychological well-being dimensions: positive relations, environmental mastery, self-acceptance, autonomy, personal growth, and purpose in life. In addition, 47% to 66% of the variance of the harmony in life was explained by the dimensions of psychological well-being within the four affective profiles. Specifically, harmony in life was significantly predicted by environmental mastery and self-acceptance across all affective profiles. However, for the low affective group high purpose in life predicted low levels of harmony in life. Conclusions. The results demonstrated that affective profiles systematically relate to psychological well-being and harmony in life. Notably, individuals categorised as self-fulfilling tended to report higher levels of both psychological well-being and harmony in life when compared with the other profiles. Meanwhile individuals in the self-destructive group reported the lowest levels of psychological well-being and harmony when compared with the three other profiles. It is proposed that self-acceptance and environmental acceptance might enable individuals to go from self-destructive to a self-fulfilling state that also involves harmony in life. PMID:24688843

Food safety objectives for Listeria monocytogenes in Spanish food sampled in cafeterias and restaurants.

PubMed

Doménech, E; Amorós, J A; Escriche, I

2011-09-01

To gain more insight into the context of food safety management by public administrations, food safety objectives must be studied. The Valencian administration quantified the prevalence of Listeria monocytogenes in cafeterias and restaurants in this region of Spain between 2002 and 2010. The results obtained from this survey are presented here for 2,262 samples of fish, salad, egg, cold meat, and mayonnaise dishes. Microbiological criteria defined for L. monocytogenes were used to differentiate acceptable and unacceptable samples; more than 99.9% of the samples were acceptable. These findings indicate that established food safety objectives are achievable, consumer health at the time of consumption can be safeguarded, and food safety management systems such as hazard analysis critical control point plans or good manufacturing practices implemented in food establishments are effective. Monitoring of foods and food safety is an important task that must continue to reduce the current L. monocytogenes prevalence of 0.1% in restaurant or cafeteria dishes, which could adversely affect consumer health.

The European Medicines Agency Review of Carfilzomib for the Treatment of Adult Patients with Multiple Myeloma Who Have Received at Least One Prior Therapy.

PubMed

Tzogani, Kyriaki; Camarero Jiménez, Jorge; Garcia, Isabel; Sancho-López, Arantxa; Martin, Marc; Moreau, Alexandre; Demolis, Pierre; Salmonson, Tomas; Bergh, Jonas; Laane, Edward; Ludwig, Heinz; Gisselbrecht, Christian; Pignatti, Francesco

2017-11-01

On November 19, 2015, a marketing authorization valid through the European Union was issued for carfilzomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.In a phase III trial in patients with relapsed MM, median progression-free survival (PFS) for patients treated with carfilzomib in combination with lenalidomide and dexamethasone (CRd) was 26.3 months versus 17.6 months for those receiving lenalidomide and dexamethasone alone (hazard ratio = 0.69; 95% confidence interval, 0.57-0.83; one-sided log-rank p value < .0001). The most frequently observed toxicity (grade ≥3, treatment arm vs. control arm) in the phase III trial included neutropenia (29.6% vs. 26.5%), anemia (17.9% vs. 17.7%), thrombocytopenia (16.8% vs. 12.3%), pneumonia (12.5% vs. 10.5%), fatigue (7.7% vs. 6.4%), hypertension (4.6% vs. 2.1%), diarrhea (3.8% vs. 4.1%), and respiratory tract infection (4.1% vs. 2.1%).The objective of this article is to summarize the scientific review of the application leading to regulatory approval in the European Union. The scientific review concluded that the gain in PFS of 8.7 months observed with the combination of CRd was considered clinically meaningful and was supported by a clear trend in overall survival benefit, although the data were not mature. The delay in disease progression appeared superior to available alternatives in the setting of relapsed MM at the time of the marketing authorization of carfilzomib. Therefore, given the overall accepted safety profile, which was considered manageable in the current context, the benefit risk for CRd was considered positive. Carfilzomib (Kyprolis) was approved in the European Union in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The addition of carfilzomib to lenalidomide and dexamethasone resulted in a clinically meaningful and statistically significant improvement of progression-free survival compared with lenalidomide and dexamethasone, which was supported by a clear trend in overall survival benefit, although the data were not mature. At the time of the marketing authorization of carfilzomib, the delay in disease progression appeared superior to available alternatives in the setting of relapsed multiple myeloma. In terms of safety, the overall accepted safety profile was considered manageable. © AlphaMed Press 2017.

76 FR 77561 - Atomic Safety and Licensing Board; In the Matter of Progress Energy Florida, Inc.; (Levy County...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

...] Atomic Safety and Licensing Board; In the Matter of Progress Energy Florida, Inc.; (Levy County Nuclear... Statements) This Atomic Safety and Licensing Board hereby gives notice that it will accept oral or written..., Inc.; Establishment of Atomic Safety and Licensing Board, 74 FR 9113 (Mar. 2, 2009) (ADAMS Accession...

A Quantitative Assessment of the Factors that Influence Technology Acceptance in Emergency Response

ERIC Educational Resources Information Center

Seiter, Thomas C.

2012-01-01

Traditional models for studying user acceptance and adoption of technology focused on the factors that identify and tested the relationships forged between the user and the technology in question. In emergency response, implementing technology without user acceptance may affect the safety of the responders and citizenry. Integrating the factors…

Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. Identification of a suitable "back-up" compound for N-tert-butyl isoquine.

PubMed

O'Neill, Paul M; Shone, Alison E; Stanford, Deborah; Nixon, Gemma; Asadollahy, Eghbaleh; Park, B Kevin; Maggs, James L; Roberts, Phil; Stocks, Paul A; Biagini, Giancarlo; Bray, Patrick G; Davies, Jill; Berry, Neil; Hall, Charlotte; Rimmer, Karen; Winstanley, Peter A; Hindley, Stephen; Bambal, Ramesh B; Davis, Charles B; Bates, Martin; Gresham, Stephanie L; Brigandi, Richard A; Gomez-de-Las-Heras, Federico M; Gargallo, Domingo V; Parapini, Silvia; Vivas, Livia; Lander, Hollie; Taramelli, Donatella; Ward, Stephen A

2009-04-09

On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline amodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy group with a hydrogen, fluorine, or chlorine atom. Following antimalarial assessment and studies on mechanism of action, two candidates were selected for detailed ADME studies and in vitro and in vivo toxicological assessment. 4'-Fluoro-N-tert-butylamodiaquine (2k) was subsequently identified as a candidate for further development studies based on potent activity versus chloroquine-sensitive and resistant parasites, moderate to excellent oral bioavailability, low toxicity in in vitro studies, and an acceptable safety profile.

75 FR 27734 - Agency Information Collection Activities; Proposed Collection; Comment Request; Safety Standard...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... Glatz, Division of Policy and Planning, Office of Information Technology, Consumer Product Safety... appropriate, and other forms of information technology. Title: Safety Standard for Bicycle Helmets--16 CFR... and process for Commission acceptance of accreditation of third party conformity assessment bodies for...

Science and Safety: 'Acceptable' Risk

ERIC Educational Resources Information Center

Science News, 1976

1976-01-01

Stresses ways to answer questions related to widespread publicity - are nuclear reactors safe, will dangerous research in genetic manipulation be banned? - with emphasis on true meaning of safety as related to risks. (EB)

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

The efficacy and safety of palonosetron compared with granisetron in preventing highly emetogenic chemotherapy-induced vomiting in the Chinese cancer patients: a phase II, multicenter, randomized, double-blind, parallel, comparative clinical trial.

PubMed

Yu, Zhaocai; Liu, Wenchao; Wang, Ling; Liang, Houjie; Huang, Ying; Si, Xiaoming; Zhang, Helong; Liu, Duhu; Zhang, Hongmei

2009-01-01

This clinical trial was conducted to evaluate the efficacy and safety of Palonosetron in preventing chemotherapy-induced vomiting (CIV) among the Chinese cancer patients. Two hundred and forty patients were scheduled to be enrolled and randomized to receive a single intravenous dose of palonosetron 0.25 mg, or granisetron 3 mg, 30 min before receiving highly emetogenic chemotherapy. The primary efficacy endpoint was the complete response (CR) rate for acute CIV (during the 0-24-h interval after chemotherapy). Secondary endpoints included the CR rates for delayed CIV (more than 24 h after chemotherapy). Two hundred and eight patients were accrued and received study medication. CR rates for acute CIV were 82.69% for palonosetron and 72.12% for granisetron, which demonstrated that palonosetron was not inferior to granisetron in preventing acute CIV. Comparisons of CR rates for delayed CIV yielded no statistical difference between palonosetron and granisetron groups and did not reveal non-inferiority of palonosetron to granisetron. Adverse events were mostly mild to moderate, with quite low rates among the two groups. A single dose (0.25 mg) of palonosetron is not inferior to a single dose (3 mg) of granisetron in preventing CIV and possesses an acceptable safety profile in the Chinese population.

Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan.

PubMed

Ninomiya, Haruhiko; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Nishiwaki, Kaichi; Matsumura, Itaru; Shichishima, Tsutomu; Okamoto, Shinichiro; Nishimura, Jun-Ichi; Ohyashiki, Kazuma; Nakao, Shinji; Ando, Kiyoshi; Kanda, Yoshinobu; Kawaguchi, Tatsuya; Nakakuma, Hideki; Harada, Daisuke; Akiyama, Hirozumi; Kinoshita, Taroh; Ozawa, Keiya; Omine, Mitsuhiro; Kanakura, Yuzuru

2016-11-01

Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count ≥150 × 10 9 /L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention.

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

Assessing the utility of TAM, TPB, and UTAUT for advanced driver assistance systems.

PubMed

Rahman, Md Mahmudur; Lesch, Mary F; Horrey, William J; Strawderman, Lesley

2017-11-01

Advanced Driver Assistance Systems (ADAS) are intended to enhance driver performance and improve transportation safety. The potential benefits of these technologies, such as reduction in number of crashes, enhancing driver comfort or convenience, decreasing environmental impact, etc., have been acknowledged by transportation safety researchers and federal transportation agencies. Although these systems afford safety advantages, they may also challenge the traditional role of drivers in operating vehicles. Driver acceptance, therefore, is essential for the implementation of these systems into the transportation system. Recognizing the need for research into the factors affecting driver acceptance, this study assessed the utility of the Technology Acceptance Model (TAM), the Theory of Planned Behavior (TPB), and the Unified Theory of Acceptance and Use of Technology (UTAUT) for modelling driver acceptance in terms of Behavioral Intention to use an ADAS. Each of these models propose a set of factors that influence acceptance of a technology. Data collection was done using two approaches: a driving simulator approach and an online survey approach. In both approaches, participants interacted with either a fatigue monitoring system or an adaptive cruise control system combined with a lane-keeping system. Based on their experience, participants responded to several survey questions to indicate their attitude toward using the ADAS and their perception of its usefulness, usability, etc. A sample of 430 surveys were collected for this study. Results found that all the models (TAM, TPB, and UTAUT) can explain driver acceptance with their proposed sets of factors, each explaining 71% or more of the variability in Behavioral Intention. Among the models, TAM was found to perform the best in modelling driver acceptance followed by TPB. The findings of this study confirm that these models can be applied to ADAS technologies and that they provide a basis for understanding driver acceptance. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Phase III, single-arm study of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5mg) in postmenarcheal adolescents.

PubMed

Gemzell-Danielsson, Kristina; Buhling, Kai J; Dermout, Sylvia M; Lukkari-Lax, Eeva; Montegriffo, Elaine; Apter, Dan

2016-06-01

To assess the safety profile of the low-dose levonorgestrel intrauterine system (LNG-IUS) total content 13.5mg (average approximate release rate 8μg/24h over the first year; LNG-IUS 8; Jaydess®) in adolescents. In a Phase III study in 36 European centers, 304 healthy nulliparous or parous postmenarcheal adolescents (12-17years) received LNG-IUS 8 for 12months. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included: serious TEAEs, adverse events of special interest, overall user satisfaction, discontinuation rate at 12months, and Pearl Index. LNG-IUS 8 placement was successful in 303/304 participants (99.7%). Overall, 82.6% of participants reported TEAEs, and serious TEAEs and serious study drug-related TEAEs were reported by 7.6% and 1.0% of participants, respectively. No cases of pelvic inflammatory disease, ectopic pregnancy, or uterine perforation were reported. No pregnancies were reported during the 12-month study. At Month 12/study end, the overall user satisfaction rate was 83.9%. Overall, 51 participants (16.8%) prematurely discontinued the study before 12months; 13.8% of participants discontinued owing to TEAEs. No new or unexpected safety events were associated with the low-dose LNG-IUS 8. The safety profile of LNG-IUS 8 in adolescents was consistent with that previously reported in adults. The high overall user-satisfaction rate at study end and the low discontinuation rate over 12months demonstrate that LNG-IUS 8 is a highly acceptable contraceptive method among adolescents. This study is the first to assess the low-dose levonorgestrel intrauterine system LNG-IUS 8 (average approximate release rate 8μg/24h over the first year and total content 13.5mg) specifically in females<18years of age and confirms the safety and efficacy of LNG-IUS 8 in an adolescent population. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.

PubMed

Schwarz, Tino F; Galaj, Andrzej; Spaczynski, Marek; Wysocki, Jacek; Kaufmann, Andreas M; Poncelet, Sylviane; Suryakiran, Pemmaraju V; Folschweiller, Nicolas; Thomas, Florence; Lin, Lan; Struyf, Frank

2017-11-01

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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...

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data.

PubMed

Moffa, Adriano H; Brunoni, André R; Fregni, Felipe; Palm, Ulrich; Padberg, Frank; Blumberger, Daniel M; Daskalakis, Zafiris J; Bennabi, Djamila; Haffen, Emmanuel; Alonzo, Angelo; Loo, Colleen K

2017-10-15

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been increasingly used for major depressive disorder (MDD) treatment. Although studies in healthy volunteers showed that the technique is well-tolerated, tDCS safety and acceptability have not been sufficiently explored in patients with MDD. We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis. Primary outcomes were safety (rate of adverse events) and acceptability (rate of dropouts). Secondary outcomes were clinical, demographic and treatment predictors of the primary outcomes. Dropout rates between active (8.8%) and sham (12%) groups were not significantly different (OR= 0.7, p=0.38). Adverse event rates between active (73.5%) and sham (68.3%) groups were not significantly different (OR= 1.4, p= 0.23). Higher current densities were associated with lower adverse event rates. Dropout reasons were not systematically reported and adverse events were not collected using questionnaires standardized across studies. Active tDCS is as acceptable and safe as sham tDCS, as found in randomized clinical trials of MDD. Copyright © 2017. Published by Elsevier B.V.

Space Station crew safety alternatives study. Volume 5: Space Station safety plan

NASA Technical Reports Server (NTRS)

Mead, G. H.; Peercy, R. L., Jr.; Raasch, R. F.

1985-01-01

The Space Station Safety Plan has been prepared as an adjunct to the subject contract final report, suggesting the tasks and implementation procedures to ensure that threats are addressed and resolution strategy options identified and incorporated into the space station program. The safety program's approach is to realize minimum risk exposure without levying undue design and operational constraints. Safety objectives and risk acceptances are discussed.

Semiquantitative analysis of gaps in microbiological performance of fish processing sector implementing current food safety management systems: a case study.

PubMed

Onjong, Hillary Adawo; Wangoh, John; Njage, Patrick Murigu Kamau

2014-08-01

Fish processing plants still face microbial food safety-related product rejections and the associated economic losses, although they implement legislation, with well-established quality assurance guidelines and standards. We assessed the microbial performance of core control and assurance activities of fish exporting processors to offer suggestions for improvement using a case study. A microbiological assessment scheme was used to systematically analyze microbial counts in six selected critical sampling locations (CSLs). Nine small-, medium- and large-sized companies implementing current food safety management systems (FSMS) were studied. Samples were collected three times on each occasion (n = 324). Microbial indicators representing food safety, plant and personnel hygiene, and overall microbiological performance were analyzed. Microbiological distribution and safety profile levels for the CSLs were calculated. Performance of core control and assurance activities of the FSMS was also diagnosed using an FSMS diagnostic instrument. Final fish products from 67% of the companies were within the legally accepted microbiological limits. Salmonella was absent in all CSLs. Hands or gloves of workers from the majority of companies were highly contaminated with Staphylococcus aureus at levels above the recommended limits. Large-sized companies performed better in Enterobacteriaceae, Escherichia coli, and S. aureus than medium- and small-sized ones in a majority of the CSLs, including receipt of raw fish material, heading and gutting, and the condition of the fish processing tables and facilities before cleaning and sanitation. Fish products of 33% (3 of 9) of the companies and handling surfaces of 22% (2 of 9) of the companies showed high variability in Enterobacteriaceae counts. High variability in total viable counts and Enterobacteriaceae was noted on fish products and handling surfaces. Specific recommendations were made in core control and assurance activities associated with sampling locations showing poor performance.

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.

Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance.

PubMed

Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Suzuki, Nahoko; Murakami, Masahiro

2017-12-01

To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review.

PubMed

McKinnon, Ross A; Cook, Matthew; Liauw, Winston; Marabani, Mona; Marschner, Ian C; Packer, Nicolle H; Prins, Johannes B

2018-02-01

The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern. The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps. A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies. The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups. There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.

14 CFR 189.3 - Kinds of messages accepted or relayed.

Code of Federal Regulations, 2012 CFR

2012-01-01

... address: (1) Distress messages and distress traffic. (2) Messages concerning the safety of human life. (3) Flight safety messages concerning— (i) Air traffic control, including— (A) Messages concerning aircraft...

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.

78 FR 54280 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-03

... safety-related batteries would remain operable if all the inter-cell and terminal connections were at the... new acceptance criteria for total battery connection resistance to ensure that the safety-related batteries can perform their specified safety function. Basis for proposed no significant hazards...

75 FR 15484 - Railroad Safety Technology Program Grant Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... governments for projects that have a public benefit of improved railroad safety and efficiency. The program... State and local governments for projects * * * that have a public benefit of improved safety and network... minimum 20 percent grantee cost share (cash or in-kind) match requirement. DATES: FRA will begin accepting...

Simulating Geriatric Home Safety Assessments in a Three-Dimensional Virtual World

ERIC Educational Resources Information Center

Andrade, Allen D.; Cifuentes, Pedro; Mintzer, Michael J.; Roos, Bernard A.; Anam, Ramanakumar; Ruiz, Jorge G.

2012-01-01

Virtual worlds could offer inexpensive and safe three-dimensional environments in which medical trainees can learn to identify home safety hazards. Our aim was to evaluate the feasibility, usability, and acceptability of virtual worlds for geriatric home safety assessments and to correlate performance efficiency in hazard identification with…

The relationship between physician burnout and quality of healthcare in terms of safety and acceptability: a systematic review

PubMed Central

Dewa, Carolyn S; Loong, Desmond; Bonato, Sarah; Trojanowski, Lucy

2017-01-01

Objectives This study reviews the current state of the published peer-reviewed literature related to physician burnout and two quality of care dimensions. The purpose of this systematic literature review is to address the question, ‘How does physician burnout affect the quality of healthcare related to the dimensions of acceptability and safety?’ Design Using a multiphase screening process, this systematic literature review is based on publically available peer-reviewed studies published between 2002 and 2017. Six electronic databases were searched: (1) MEDLINE Current, (2) MEDLINE In-process, (3) MEDLINE Epub Ahead of Print, (4) PsycINFO, (5) Embase and (6) Web of Science. Setting Physicians practicing in civilian settings. Participants Practicing physicians who have completed training. Primary and secondary outcome measures Quality of healthcare related to acceptability (ie, patient satisfaction, physician communication and physician attitudes) and safety (ie, minimising risks or harm to patients). Results 4114 unique citations were identified. Of these, 12 articles were included in the review. Two studies were rated as having high risk of bias and 10 as having moderate risk. Four studies were conducted in North America, four in Europe, one in the Middle East and three in East Asia. Results of this systematic literature review suggest there is moderate evidence that burnout is associated with safety-related quality of care. Because of the variability in the way patient acceptability-related quality of care was measured and the inconsistency in study findings, the evidence supporting the relationship between burnout and patient acceptability-related quality of care is less strong. Conclusions The focus on direct care-related quality highlights additional ways that physician burnout affects the healthcare system. These studies can help to inform decisions about how to improve patient care by addressing physician burnout. Continued work looking at the relationship between dimensions of acceptability-related quality of care measures and burnout is needed to advance the field. PMID:28637730

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

PubMed

Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Risk-based Spacecraft Fire Safety Experiments

NASA Technical Reports Server (NTRS)

Apostolakis, G.; Catton, I.; Issacci, F.; Paulos, T.; Jones, S.; Paxton, K.; Paul, M.

1992-01-01

Viewgraphs on risk-based spacecraft fire safety experiments are presented. Spacecraft fire risk can never be reduced to a zero probability. Probabilistic risk assessment is a tool to reduce risk to an acceptable level.

49 CFR 180.511 - Acceptable results of inspections and tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Safety system inspection. A tank car successfully passes the safety system inspection when each thermal..., distortion, excessive permanent expansion, or other evidence of weakness that might render the tank car...

Once and for All.

ERIC Educational Resources Information Center

Wright, Dorothy

1984-01-01

A Connecticut district's stringent asbestos removal and testing program is described, which applies a modified National Institute of Occupational Safety and Health-Occupational Safety and Health Administration (NIOSH-OSHA) test as a standard of acceptable removal. (MJL)

Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer.

PubMed

Moehler, Markus; Mahlberg, Rolf; Heinemann, Volker; Obermannová, Radka; Kubala, Eugen; Melichar, Bohuslav; Weinmann, Arndt; Scigalla, Paul; Tesařová, Marietta; Janda, Petr; Hédouin-Biville, Fabienne; Mansoor, Wasat

2017-03-01

This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m 2 followed by oxaliplatin 130 mg/m 2 (maximum 8 cycles) and then S-1 [20 mg/m 2 (cohort 1) or 25 mg/m 2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. DLT was reported for two of the five patients in cohort 2, defining 20 mg/m 2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m 2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. The promising activity of EOS (S-1 dose level, 25 mg/m 2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

Metastatic renal cell carcinoma: CT-guided immunotherapy as a technically feasible and safe approach to delivery of gene therapy for treatment.

PubMed

Suh, Robert D; Goldin, Jonathan G; Wallace, Amanda B; Sheehan, Ramon E; Heinze, Stefan B; Gitlitz, Barbara J; Figlin, Robert A

2004-05-01

To assess the technical feasibility and safety of weekly outpatient percutaneous computed tomographic (CT)-guided intratumoral injections of interleukin-2 (IL-2) plasmid DNA in a wide variety of superficial and deep tumor sites. Twenty-nine patients with metastatic renal cell carcinoma and a total of 30 lesions measuring 1.0 cm(2) or greater in accessible thoracic (n = 15) or abdominal (n = 15) locations underwent up to three cycles of six weekly intratumoral IL-2 plasmid DNA injections. CT was used to guide needle placement and injection. After injection cycle 1, patients whose tumors demonstrated stable (< or =25% increase and < or =50% decrease in product of lesion diameters) or decreased size (>50% decrease in product of lesion diameters) advanced to injection cycle 2. Patients whose lesions decreased in size by more than 50% over the course of injection cycle 2 were eligible to begin injection cycle 3. An acceptable safety and technical feasibility profile for this technique was deemed to be (a) a safety and feasibility profile similar to that of single-needle biopsy and (b) an absence of serious adverse events (as defined in Title 21 of the Code of Federal Regulations) and/or unacceptable toxicities (as graded according to the National Cancer Institute Common Toxicity Criteria). A total of 284 intratumoral injections were performed, with a mean of 9.8 injections (range, 6-18 injections) received by each patient. Technical success (needle placement and injection of gene therapy agent) was achieved in all cases. Complications were experienced after 42 (14.8%) of the 284 injections. The most common complication was pneumothorax (at 32 [28.6%] of 112 intrathoracic injections), for which only one patient required catheter drainage. Complications occurred randomly throughout injection cycles and did not appear to increase as patients received more injections (P =.532). No patient experienced serious adverse events or unacceptable toxicities. Percutaneous CT-guided intratumoral immunotherapy injections are technically feasible and can be safely performed.

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.

Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma.

PubMed

Kumar, Shaji; Kaufman, Jonathan L; Gasparetto, Cristina; Mikhael, Joseph; Vij, Ravi; Pegourie, Brigitte; Benboubker, Lofti; Facon, Thierry; Amiot, Martine; Moreau, Philippe; Punnoose, Elizabeth A; Alzate, Stefanie; Dunbar, Martin; Xu, Tu; Agarwal, Suresh K; Enschede, Sari Heitner; Leverson, Joel D; Ross, Jeremy A; Maciag, Paulo C; Verdugo, Maria; Touzeau, Cyrille

2017-11-30

Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in multiple myeloma (MM) cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-X L and MCL-1. In this phase 1 study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added on progression during treatment. Sixty-six patients were enrolled (30, dose-escalation cohorts; 36, safety expansion). Patients received a median of 5 prior therapies (range, 1-15); 61% were bortezomib and lenalidomide double refractory, and 46% had t(11;14). Venetoclax was generally well tolerated. Most common adverse events included mild gastrointestinal symptoms (nausea [47%], diarrhea [36%], vomiting [21%]). Cytopenias were the most common grade 3/4 events, with thrombocytopenia (32%), neutropenia (27%), anemia (23%), and leukopenia (23%) reported. The overall response rate (ORR) was 21% (14/66), and 15% achieved very good partial response or better (≥VGPR). Most responses (12/14 [86%]) were reported in patients with t(11;14). In this group, ORR was 40%, with 27% of patients achieving ≥VGPR. Biomarker analysis confirmed that response to venetoclax correlated with higher BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios. Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile and evidence of single-agent antimyeloma activity in patients with relapsed/refractory MM, predominantly in patients with t(11;14) abnormality and those with a favorable BCL2 family profile. Registered at www.clinicaltrials.gov: #NCT01794520. © 2017 by The American Society of Hematology.

A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

PubMed

Cervigni, Mauro; Sommariva, Monica; Tenaglia, Raffaele; Porru, Daniele; Ostardo, Edoardo; Giammò, Alessandro; Trevisan, Silvia; Frangione, Valeria; Ciani, Oriana; Tarricone, Rosanna; Pappagallo, Giovanni L

2017-04-01

Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril ® , IBSA) to dimethyl sulfoxide (DMSO). Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile. © 2016 Wiley Periodicals, Inc.

Evaluating the U.S. Food Safety Modernization Act Produce Safety Rule Standard for Microbial Quality of Agricultural Water for Growing Produce.

PubMed

Havelaar, Arie H; Vazquez, Kathleen M; Topalcengiz, Zeynal; Muñoz-Carpena, Rafael; Danyluk, Michelle D

2017-10-09

The U.S. Food and Drug Administration (FDA) has defined standards for the microbial quality of agricultural surface water used for irrigation. According to the FDA produce safety rule (PSR), a microbial water quality profile requires analysis of a minimum of 20 samples for Escherichia coli over 2 to 4 years. The geometric mean (GM) level of E. coli should not exceed 126 CFU/100 mL, and the statistical threshold value (STV) should not exceed 410 CFU/100 mL. The water quality profile should be updated by analysis of a minimum of five samples per year. We used an extensive set of data on levels of E. coli and other fecal indicator organisms, the presence or absence of Salmonella, and physicochemical parameters in six agricultural irrigation ponds in West Central Florida to evaluate the empirical and theoretical basis of this PSR. We found highly variable log-transformed E. coli levels, with standard deviations exceeding those assumed in the PSR by up to threefold. Lognormal distributions provided an acceptable fit to the data in most cases but may underestimate extreme levels. Replacing censored data with the detection limit of the microbial tests underestimated the true variability, leading to biased estimates of GM and STV. Maximum likelihood estimation using truncated lognormal distributions is recommended. Twenty samples are not sufficient to characterize the bacteriological quality of irrigation ponds, and a rolling data set of five samples per year used to update GM and STV values results in highly uncertain results and delays in detecting a shift in water quality. In these ponds, E. coli was an adequate predictor of the presence of Salmonella in 150-mL samples, and turbidity was a second significant variable. The variability in levels of E. coli in agricultural water was higher than that anticipated when the PSR was finalized, and more detailed information based on mechanistic modeling is necessary to develop targeted risk management strategies.

A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).

PubMed

Sehouli, Jalid; Tomè, Oliver; Dimitrova, Desislava; Camara, Oumar; Runnebaum, Ingo Bernhard; Tessen, Hans Werner; Rautenberg, Beate; Chekerov, Radoslav; Muallem, Mustafa Zelal; Lux, Michael Patrick; Trarbach, Tanja; Gitsch, Gerald

2017-03-01

In recurrent ovarian cancer (ROC), there is a high demand on effective therapies with a mild toxicity profile. Treosulfan is an alkylating agent approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of recurrent ovarian cancer. Data on safety and efficacy for either formulation are rare. For the first time we conducted a randomized phase III study comparing both formulations in women with ROC. Patients having received at least two previous lines of chemotherapy were randomly assigned to one of two treatment arms: treosulfan i.v. 7000 mg/m 2 d1 q4w or treosulfan p.o. 600 mg/m 2 d1-28 q8w. Primary endpoint was safety regarding hematological and gastrointestinal toxicity grade III/IV, secondary endpoints were other toxicities, clinical benefit rate (CBR), time to progression (TTP), overall survival (OS) and quality of life. 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o. (122). In general treosulfan therapy was well tolerated in both treatment arms. Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. Given the safety and efficacy results treosulfan is an acceptable option for heavily pretreated OC patients. Regarding the toxicity profile the i.v. application was better tolerated with less grade III and IV toxicities.

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.

Designer milk.

PubMed

Sabikhi, Latha

2007-01-01

Dairy biotechnology is fast gaining ground in the area of altering milk composition for processing and/or animal and human health by employing nutritional and genetic approaches. Modification of the primary structure of casein, alteration in the lipid profile, increased protein recovery, milk containing nutraceuticals, and replacement for infant formula offer several advantages in the area of processing. Less fat in milk, altered fatty acid profiles to include more healthy fatty acids such as CLA and omega-fats, improved amino acid profiles, more protein, less lactose, and absence of beta-lactoglobulin (beta-LG) are some opportunities of "designing" milk for human health benefits. Transgenic technology has also produced farm animals that secrete in their milk, human lactoferrin, lysozyme, and lipase so as to simulate human milk in terms of quality and quantity of these elements that are protective to infants. Cow milk allergenicity in children could be reduced by eliminating the beta-LG gene from bovines. Animals that produce milk containing therapeutic agents such as insulin, plasma proteins, drugs, and vaccines for human health have been genetically engineered. In order to cater to animal health, transgenic animals that express in their mammary glands, various components that work against mastitis have been generated. The ultimate acceptability of the "designer" products will depend on ethical issues such as animal welfare and safety, besides better health benefits and increased profitability of products manufactured by the novel techniques.

Sufficient blood, safe blood: can we have both?

PubMed Central

2012-01-01

The decision in September 2011 in the UK to accept blood donations from non-practicing men who have sex with men (MSM) has received significant public attention. Will this rule change substantially boost the number of blood donations or will it make our blood less safe? Clearly, most European countries have a blood procurement problem. Fewer young people are donating, while the population is aging and more invasive therapies are requiring more blood. Yet if that was the reason for allowing non-practicing MSM to donate, clearly re-admission of some other, much larger populations that are currently deferred from donation should likewise be considered. As far as risks for blood safety are concerned, evidence has been provided that the current quality of infectious disease marker testing significantly mitigates against, although does not completely eradicate, risks associated with admission of donors with a high risk of carrying certain blood-transmissible agents. However, it could be argued that more effective recruitment of the non-donor pool, which is substantially larger than the group of currently ineligible donors, would be a better strategy. Recruitment of this group will benefit the availability of blood without jeopardizing the current excellent safety profile of blood. PMID:22439656

Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials.

PubMed

Mo, Yoonsun; Thomas, Michael C; Karras, George E

2016-04-01

To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications. Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS. Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS. Copyright © 2015 Elsevier Inc. All rights reserved.

Cold chain management in meat storage, distribution and retail: A review

NASA Astrophysics Data System (ADS)

Nastasijević, I.; Lakićević, B.; Petrović, Z.

2017-09-01

Meat is a perishable product with a short shelf life and therefore short selling times. Therefore, cold chain management in meat supply is of utmost importance for the maintenance of quality and safety of meat/meat products. Raw meat/meat products are likely to support the growth of pathogenic microorganisms and/or spoilage bacteria, and should be kept at temperatures that do not result in a risk to health. The cold chain should not be interrupted at all times along the meat distribution chain. The complexity of global meat supply chain, with frequently long distribution chains associated with transportation of the product within one country, from one to another country and from one to another continent, makes the solutions for the chilling and freezing regimes, as well as monitoring of time-temperature profiles, very important for the overall success in delivery of product which will be accepted by consumer for its freshness and safety levels. From recently, there are several available options for control and management of the cold chain, such as chilled and frozen storage combinations, superchilling, ionizing radiation, biopreservation, high hydrostatic pressure (HHP), active packaging, wireless sensors, supported with the software-based cold chain database (CCD).

Medication abortion: Potential for improved patient access through pharmacies.

PubMed

Raifman, Sarah; Orlando, Megan; Rafie, Sally; Grossman, Daniel

2018-05-08

To discuss the potential for improving access to early abortion care through pharmacies in the United States. Despite the growing use of medications to induce termination of early pregnancy, pharmacist involvement in abortion care is currently limited. The Food and Drug Administration's Risk Evaluation and Mitigation Strategy (REMS) for Mifeprex® (mifepristone 200 mg), the principal drug used in early medication abortion, prohibits the dispensing of the drug by prescription at pharmacies. This commentary reviews the pharmacology of medication abortion with the use of mifepristone and misoprostol, as well as aspects of service delivery and data on safety, efficacy, and acceptability. Given its safety record, mifepristone no longer fits the profile of a drug that requires an REMS. The recent implementation of pharmacy dispensing of mifepristone in community pharmacies in Australia and some provinces of Canada has improved access to medication abortion by increasing the number of medication abortion providers, particularly in rural areas. Provision of mifepristone in pharmacies, which involves dispensing and patient counseling, would likely improve access to early abortion in the United States without increasing risks to women. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Influenza immunization during pregnancy: Benefits for mother and infant

PubMed Central

Sakala, Isaac G.; Honda-Okubo, Yoshikazu; Fung, Johnson; Petrovsky, Nikolai

2016-01-01

ABSTRACT The serious consequences of influenza infection during pregnancy have been recognized for almost a century. In this article, we reviewed the evidence on the immunogenicity, safety and impact of maternal influenza immunization for both mother and child. After vaccination, pregnant women have similar protective titers of anti-influenza antibodies as non-pregnant women, demonstrating that pregnancy does not alter the trivalent inactivated influenza vaccine immune response. Studies from the United States, Europe and resource-constrained regions demonstrate that maternal vaccination is associated with increased anti-influenza antibody concentrations and protection in the newborn child as well as the immunized mother. Given the acceptable safety profile of influenza vaccines and the World Health Organization's recommendation for its use in pregnant women, maternal vaccination with inactivated influenza vaccine is a cost-effective approach to decrease influenza disease in newborns. However, as seen for influenza immunization in the elderly, the protective efficacy of current inactivated vaccines in protection of newborns is 50% at best, indicating significant room for vaccine improvement, which could potentially be achieved by addition of a safe and effective adjuvant. Thus, global deployment of inactivated influenza immunization during pregnancy would have substantial and measurable health benefits for mothers and their newborns. PMID:27494630

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.

Use of Active-Play Video Games to Enhance Aerobic Fitness in Schizophrenia: Feasibility, Safety, and Adherence.

PubMed

Kimhy, David; Khan, Samira; Ayanrouh, Lindsey; Chang, Rachel W; Hansen, Marie C; Lister, Amanda; Ballon, Jacob S; Vakhrusheva, Julia; Armstrong, Hilary F; Bartels, Matthew N; Sloan, Richard P

2016-02-01

Active-play video games have been used to enhance aerobic fitness in various clinical populations, but their use among individuals with schizophrenia has been limited. Feasibility, acceptability, safety, and adherence data were obtained for use of aerobic exercise (AE) equipment by 16 individuals with schizophrenia during a 12-week AE program consisting of three one-hour exercise sessions per week. Equipment included exercise video games for Xbox 360 with Kinect motion sensing devices and traditional exercise equipment. Most participants (81%) completed the training, attending an average of 79% of sessions. The proportion of time spent playing Xbox (39%) exceeded time spent on any other type of equipment. When using Xbox, participants played 2.24±1.59 games per session and reported high acceptability and enjoyment ratings, with no adverse events. Measures of feasibility, acceptability, adherence, and safety support the integration of active-play video games into AE training for people with schizophrenia.

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults

PubMed Central

Omosa-Manyonyi, Gloria; Mpendo, Juliet; Ruzagira, Eugene; Kilembe, William; Chomba, Elwyn; Roman, François; Bourguignon, Patricia; Koutsoukos, Marguerite; Collard, Alix; Voss, Gerald; Laufer, Dagna; Stevens, Gwynn; Hayes, Peter; Clark, Lorna; Cormier, Emmanuel; Dally, Len; Barin, Burc; Ackland, Jim; Syvertsen, Kristen; Zachariah, Devika; Anas, Kamaal; Sayeed, Eddy; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Fast, Patricia; Priddy, Frances

2015-01-01

Background Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. Methods In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. Results The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. Conclusion Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses. Trial Registration ClinicalTrials.gov NCT01264445 PMID:25961283

Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice.

PubMed

Yoshizawa, K; Kawai, K; Fujie, M; Suzuki, J; Ogawa, Y; Yajima, T; Yokomori, J

2015-11-01

To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).

What determines the acceptability of genetically modified food that can improve human nutrition?

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

Purchase, Iain F.H.

It has been predicted that by 2025 there will be an annual shortfall of cereals for feeding the human population of 68.5 million tonnes. One possible solution is the use of genetically modified (GM) crops, which are already grown extensively (59 million ha of GM crops were planted in 2002) in the USA, South America, Africa and China. Nevertheless, there is considerable disagreement about the advisability of using such crops, particularly in Europe. Obviously, the safety of the food derived from the GM crops is a primary consideration. Safety assessment relies on establishing that the food is substantially equivalent tomore » its non-GM counterpart and specific testing for allergenicity of proteins and toxicity of metabolites and the whole food. There appears to be international agreement on the principles of safety assessment. Safety to the environment is equally important, but will not be covered in this presentation. The public's perception of the risk of new technology is critical to its acceptance. Perception of risk, in turn, depends on the credibility of the source of the information and trust in the regulatory process. In many countries, the public appears to have lost its trust in the scientists and government dealing with GM food, making the acceptability of GM crops uncertain. Of equal importance are the socio-economic factors that impinge on the viability of GM produce. These include intellectual property protection, trade liberalisation (through subsidy and tariff barriers in developed countries) and the intensity of bio safety regulations. The socio-economic interests of developed and developing countries may diverge and may even be contradictory in any one country. Acceptance of GM crops will thus depend on detailed issues surrounding particular crops and economies.« less

What determines the acceptability of genetically modified food that can improve human nutrition?

PubMed

Purchase, Iain F H

2005-09-01

It has been predicted that by 2025 there will be an annual shortfall of cereals for feeding the human population of 68.5 million tones. One possible solution is the use of genetically modified (GM) crops, which are already grown extensively (59 million ha of GM crops were planted in 2002) in the USA, South America, Africa and China. Nevertheless, there is considerable disagreement about the advisability of using such crops, particularly in Europe. Obviously, the safety of the food derived from the GM crops is a primary consideration. Safety assessment relies on establishing that the food is substantially equivalent to its non-GM counterpart and specific testing for allergenicity of proteins and toxicity of metabolites and the whole food. There appears to be international agreement on the principles of safety assessment. Safety to the environment is equally important, but will not be covered in this presentation. The public's perception of the risk of new technology is critical to its acceptance. Perception of risk, in turn, depends on the credibility of the source of the information and trust in the regulatory process. In many countries, the public appears to have lost its trust in the scientists and government dealing with GM food, making the acceptability of GM crops uncertain. Of equal importance are the socio-economic factors that impinge on the viability of GM produce. These include intellectual property protection, trade liberalization (through subsidy and tariff barriers in developed countries) and the intensity of bio safety regulations. The socio-economic interests of developed and developing countries may diverge and may even be contradictory in any one country. Acceptance of GM crops will thus depend on detailed issues surrounding particular crops and economies.

The relationship between resident burnout and safety-related and acceptability-related quality of healthcare: a systematic literature review.

PubMed

Dewa, Carolyn S; Loong, Desmond; Bonato, Sarah; Trojanowski, Lucy; Rea, Margaret

2017-11-09

There has been increasing interest in examining the relationship between physician wellbeing and quality of patient care. However, few reviews have specifically focused on resident burnout and quality of patient care. The purpose of this systematic literature review of the current scientific literature is to address the question, "How does resident burnout affect the quality of healthcare related to the dimensions of acceptability and safety?" This systematic literature review uses a multi-step screening process of publicly available peer-reviewed studies from five electronic databases: (1) Medline Current, (2) Medline In-process, (3) PsycINFO, (4) Embase, and (5) Web of Science. The electronic literature search resulted in the identification of 4638 unique citations. Of these, 10 articles were included in the review. Studies were assessed for risk of bias. Of the 10 studies that met the inclusion criteria, eight were conducted in the US, one in The Netherlands, and one in Mexico. Eight of the 10 studies focused on patient safety. The results of these included studies suggest there is moderate evidence that burnout is associated with patient safety (i.e., resident self-perceived medical errors and sub-optimal care). There is less evidence that specific dimensions of burnout are related to acceptability (i.e., quality of care, communication with patients). The results of this systematic literature review suggest a relationship between patient safety and burnout. These results potentially have important implications for the medical training milieu because residents are still in training and at the same time are asked to teach students. The results also indicate a need for more evidence-based interventions that support continued research examining quality of care measures, especially as they relate to acceptability.

Pilot Study of an Active Screen Time Game Correlates with Improved Physical Fitness in Minority Elementary School Youth

PubMed Central

Berry, Diane; Maloney, Ann E.; Sikich, Linmarie

2012-01-01

Abstract Objective The aim of our feasibility study was to examine the acceptability and utility of “Dance Dance Revolution” (DDR) (Konami of America, Redwood City, CA)) to increase physical fitness in 8–11-year-old black and Hispanic youth. Subjects and Methods Twenty-eight 4th and 5th grade children attending an afterschool program participated. Outcomes included physical activity, physical fitness, use of home DDR, survey of safety and acceptability, anthropometrics, and fasting metabolic profile measured at baseline, 12 weeks, and 30 weeks. Results At 12 weeks, physical fitness (maximum O2 uptake [VO2max]) increased by 4.9±9.9 percent and was sustained through 30 weeks, when the VO2max was 105.0±9.9 percent (range, 93.0–133.9 percent) of baseline values. Absolute VO2max increased by 2.97±4.99 mL/kg/minute (95% confidence interval 0.75–5.19, P=0.013). Participants maintained an average of 1.12 hours/day of increased movement to music. Trends suggested increased total moderate–vigorous physical activity, decreased light activity, and a modest increase in sedentary screen time. There were no significant changes in body mass index, fasting lipids, or glucose. Participants and parents approved of the activity. Conclusion DDR appears feasible and acceptable to minority youth. DDR may increase moderate–vigorous physical activity and improve physical fitness in at-risk populations. PMID:26196430

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

Open-label extension studies: do they provide meaningful information on the safety of new drugs?

PubMed

Day, Richard O; Williams, Kenneth M

2007-01-01

The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the time of entry into the open-label extension study. Negative aspects of open-label extension studies revolve around their use as a marketing tool, as they build a market for the drug and generate pressure for subsidised access to the drug from consumers and their physicians. Consumers, institutions where these studies are conducted and research ethics committees need to be convinced of the motives, as well as the quality, of the open-label extension study and its execution before supporting such studies. Open-label extension studies do have a legitimate but limited place in the clinical development of new medicines. The negative perceptions about these studies have arisen because of perversion of acceptable rationales for this type of study and a failure to recognise (or disclose) the limitations resulting from the inherent weaknesses in their design. Increased human exposure to a new medicine under reasonably controlled circumstances to increase confidence in the safety of the medicine is an acceptable rationale for an open-label extension study, and a useful activity to increase the knowledge of the safety profile of a new medicine. However, this goal is increasingly being achieved by means other than open-label extension studies.

Bowel preparations for colonoscopy: an RCT.

PubMed

Di Nardo, Giovanni; Aloi, Marina; Cucchiara, Salvatore; Spada, Cristiano; Hassan, Cesare; Civitelli, Fortunata; Nuti, Federica; Ziparo, Chiara; Pession, Andrea; Lima, Mario; La Torre, Giuseppe; Oliva, Salvatore

2014-08-01

The ideal preparation regimen for pediatric colonoscopy remains elusive, and available preparations continue to represent a challenge for children. The aim of this study was to compare the efficacy, safety, tolerability, and acceptance of 4 methods of bowel cleansing before colonoscopy in children. This randomized, investigator-blinded, noninferiority trial enrolled all children aged 2 to 18 years undergoing elective colonoscopy in a referral center for pediatric gastroenterology. Patients were randomly assigned to receive polyethylene glycol (PEG) 4000 with simethicon (PEG-ELS group) or PEG-4000 with citrates and simethicone plus bisacodyl (PEG-CS+Bisacodyl group), or PEG 3350 with ascorbic acid (PEG-Asc group), or sodium picosulfate plus magnesium oxide and citric acid (NaPico+MgCit group). Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale. The primary end point was overall colon cleansing. Tolerability, acceptability, and compliance were also evaluated. Two hundred ninety-nine patients were randomly allocated to the 4 groups. In the per-protocol analysis, PEG-CS+Bisacodyl, PEG-Asc, and NaPico+MgCit were noninferior to PEG-ELS in bowel-cleansing efficacy of both the whole colon (P = .910) and colonic segments. No serious adverse events occurred in any group. Rates of tolerability, acceptability, and compliance were significantly higher in the NaPico+MgCit group. Low-volume PEG preparations (PEG-CS+Bisacodyl, PEG-Asc) and NaPico+MgCit are noninferior to PEG-ELS in children, representing an attractive alternative to high-volume regimens in clinical practice. Because of the higher tolerability and acceptability profile, NaPico+MgCit would appear as the most suitable regimen for bowel preparation in children. Copyright © 2014 by the American Academy of Pediatrics.

The emerging profile of cross-resistance among the nonnucleoside HIV-1 reverse transcriptase inhibitors.

PubMed

Sluis-Cremer, Nicolas

2014-07-31

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance.

The Emerging Profile of Cross-Resistance among the Nonnucleoside HIV-1 Reverse Transcriptase Inhibitors

PubMed Central

Sluis-Cremer, Nicolas

2014-01-01

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are widely used to treat HIV-1-infected individuals; indeed most first-line antiretroviral therapies typically include one NNRTI in combination with two nucleoside analogs. In 2008, the next-generation NNRTI etravirine was approved for the treatment of HIV-infected antiretroviral therapy-experienced individuals, including those with prior NNRTI exposure. NNRTIs are also increasingly being included in strategies to prevent HIV-1 infection. For example: (1) nevirapine is used to prevent mother-to-child transmission; (2) the ASPIRE (MTN 020) study will test whether a vaginal ring containing dapivirine can prevent HIV-1 infection in women; (3) a microbicide gel formulation containing the urea-PETT derivative MIV-150 is in a phase I study to evaluate safety, pharmacokinetics, pharmacodynamics and acceptability; and (4) a long acting rilpivirine formulation is under-development for pre-exposure prophylaxis. Given their widespread use, particularly in resource-limited settings, as well as their low genetic barriers to resistance, there are concerns about overlapping resistance between the different NNRTIs. Consequently, a better understanding of the resistance and cross-resistance profiles among the NNRTI class is important for predicting response to treatment, and surveillance of transmitted drug-resistance. PMID:25089538

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

PubMed Central

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-01-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

PubMed

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-08-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to <18-year-old children and adolescents at risk of influenza-related complications.

PubMed

Diez-Domingo, Javier; de Martino, Maurizio; Lopez, Jose Garcia-Sicilia; Zuccotti, Gian Vincenzo; Icardi, Giancarlo; Villani, Alberto; Moreno-Perez, David; Hernández, María Méndez; Aldeán, Javier Álvarez; Mateen, Ahmed Abdul; Enweonye, Igwebuike; de Rooij, Richard; Chandra, Richa

2016-08-01

This descriptive, non-comparative, phase III study evaluated the safety and tolerability of cell culture-derived (TIVc) and egg-derived (TIV) seasonal influenza vaccines in children at risk of influenza-related complications. Four hundred and thirty subjects were randomized 2:1 to TIVc or TIV. Subjects aged 3 to <9 years received one dose (if previously vaccinated, n=89) or two doses (if not previously vaccinated, n=124) of the study vaccines; the 9 to <18-year-olds (n=213) received one dose. Reactogenicity was assessed for 7 days after vaccination; safety was monitored for 6 months. After any vaccination, the most frequently reported solicited local adverse event (AE) was tenderness/pain (TIVc 44%, 66%, 53% and TIV 56%, 51%, 65% in the age groups 3 to <6 years, 6 to <9 years, and 9 to <18 years, respectively) and the systemic AE was irritability (22% TIVc, 24% TIV) in 3 to <6-year-olds and headache in 6 to <9-year-olds (20% TIVc, 13% TIV) and 9 to <18-year-olds (21% TIVc, 26% TIV). There were no cases of severe fever (≥40°C). No vaccine-related serious AEs were noted. New onset of chronic disease was reported in ≤1% of subjects. TIVc and TIV had acceptable tolerability and similar safety profiles in at-risk children (NCT01998477). Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Alternative food safety intervention technologies

USDA-ARS?s Scientific Manuscript database

Alternative nonthermal and thermal food safety interventions are gaining acceptance by the food processing industry and consumers. These technologies include high pressure processing, ultraviolet and pulsed light, ionizing radiation, pulsed and radiofrequency electric fields, cold atmospheric plasm...

76 FR 77329 - Schedules of Controlled Substances: Placement of Carisoprodol Into Schedule IV

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... lifetime for a non- medical reason. Id. at 89. While observing that the yearly estimates ``may remain... FDA approval as the sine qua non of the ``currently accepted medical use'' and ``accepted safety for...

Administrative goals and safety standards for hazard control on forested recreation sites

Treesearch

Lee A. Paine

1973-01-01

For efficient control of tree hazard on recreation sites, a specific administrative goal must be selected. A safety standard designed to achieve the selected goal and a uniform hazard-rating procedure will then promote a consistent level of safety at an acceptable cost. Safety standards can be established with the aid of data for past years, and dollar evaluations are...

Clinical acceptability study of micronized purified flavonoid fraction 1000 mg tablets versus 500 mg tablets in patients suffering acute hemorrhoidal disease.

PubMed

Shelygin, Yuri; Krivokapic, Zoran; Frolov, S A; Kostarev, I V; Astashov, V L; Vasiliev, S V; Lakhin, A V; Rodoman, G V; Soloviev, A O; Stoyko, Y M; Khitaryan, A G; Nechay, I A

2016-11-01

To compare the clinical acceptability of micronized purified flavonoid fraction (MPFF) 1000 mg with MPFF 500 mg tablets, administered at the same daily dose in patients suffering non-complicated acute hemorrhoids. MPFF is an established treatment for hemorrhoidal disease. This was a double-blind, multi-center, randomized study. Patients took either MPFF 1000 mg or 500 mg tablets for 7 days (daily dose; 3 g over 4 days followed by 2 g over 3 days). Adverse events were recorded in a patient diary. On day 7, anal pain and bleeding were assessed (visual analog scale [VAS] and Dimitroulopoulos scale, respectively). Patients (162) were randomized to MPFF 1000 mg (79) and MPFF 500 mg (83). No serious adverse events (AEs) occurred; 10 emergent AEs were considered treatment-related (6 for MPFF 1000 mg and 4 for 500 mg). Both regimens were associated with significant reduction in anal pain (VAS); -2.37 cm MPFF 1000 mg (P < 0.001) and -2.17 cm 500 mg (P < 0.001), with a slight trend in favor of MPFF 1000 mg (mean global reduction -2.27 cm, P < 0.001). Bleeding improved significantly in both groups of patients, 56% of patients on MPFF 1000 mg versus 61% on MPFF 500 mg. Bleeding ceased after treatment in 47% patients on MPFF 1000 mg versus 54% on 500 mg. After 7 days of treatment with MPFF at the same daily dose, both regimens reduced anal pain and bleeding. MPFF 1000 mg had a comparable safety profile to MPFF 500 mg, with the advantage of fewer tablets. Key limitations: Safety study.

Incorporating patient-preference evidence into regulatory decision making.

PubMed

Ho, Martin P; Gonzalez, Juan Marcos; Lerner, Herbert P; Neuland, Carolyn Y; Whang, Joyce M; McMurry-Heath, Michelle; Hauber, A Brett; Irony, Telba

2015-10-01

Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health. Five-hundred and forty United States adults with body mass index (BMI) ≥ 30 kg/m(2) evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey. Discrete-choice experiments were used to quantify the importance of safety, effectiveness, and other attributes of weight-loss devices to obese respondents. A tool based on these measures is being used to inform benefit-risk assessments for premarket approval of medical devices. Respondent choices yielded preference scores indicating their relative value for attributes of weight-loss devices in this study. We developed a tool to estimate the minimum weight loss acceptable by a patient to receive a device with a given risk profile and the maximum mortality risk tolerable in exchange for a given weight loss. For example, to accept a device with 0.01 % mortality risk, a risk tolerant patient will require about 10 % total body weight loss lasting 5 years. Patient preference evidence was used make regulatory decision making more patient-centered. In addition, we captured the heterogeneity of patient preferences allowing market approval of effective devices for risk tolerant patients. CDRH is using the study tool to define minimum clinical effectiveness to evaluate new weight-loss devices. The methods presented can be applied to a wide variety of medical products. This study supports the ongoing development of a guidance document on incorporating patient preferences into medical-device premarket approval decisions.

Oakland County Science Safety Series: Reference Guide for Elementary Science.

ERIC Educational Resources Information Center

Crowder, Betty Pogue; And Others

This reference guide is designed to organize and suggest acceptable practices and procedures for dealing with safety in elementary science instruction. It is intended as a reference for teachers, administrators, and other school staff in planning for science activities and in making daily safety decisions. Topics covered in the guide include: (1)…

Oakland County Science Safety Series: Reference Guide for Biology.

ERIC Educational Resources Information Center

Bury, Dan; And Others

This reference guide is designed to organize and suggest acceptable practices and procedures for dealing with safety in the area of biology instruction. It is intended as a reference for teachers, administrators, and other school staff in planning for science activities and in making daily safety decisions. Discussions deal with responsibility for…

10 CFR Appendix A to Subpart B of... - General Statement of Safety Basis Policy

Code of Federal Regulations, 2011 CFR

2011-01-01

... for the design and construction of a new DOE nuclear facility or a major modification to an existing... acceptable nuclear safety design criteria for use in preparing a preliminary documented safety analysis. As a... mitigate hazards to workers, the public, or the environment. They include (1) physical, design, structural...

75 FR 24710 - Determination That BREVIBLOC (Esmolol Hydrochloride) Injection, 250 Milligrams/Milliliter, 10...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-05

..., Was Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration... from sale for reasons of safety or effectiveness. This determination means the agency will not accept... of safety or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for...

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

[Acceptance and rejection of vasectomy in rural males].

PubMed

García Moreno, Juan; Solano Sainos, Luis Miguel

2005-01-01

One problem in rural population is the gap between coverage of contraception and scant masculine participation, which could be due to lack of information of to other sociocultural factors. We investigated, in two stages, the characteristics or the profile of the sexual and reproductive behavior of males in an exploratory study by means of focus groups to determine their relevant motivations and characteristics and subsequently, a structured questionnaire to ascertain the magnitude of the factors explored. The population corresponded to zones of rural hospital medical services zones of medical services in seven ethnic groups of the Mexican Republic and included men who accepted and who rejected vasectomy. The profile of males who accepted vasectomy allowed to determine that there exist a unsatisfied demand for contraceptive protection and the desire of not having additional children; in addition, we found that the decision to accept vasectomy is determined to a greater extent for reasons different from that of information on the contraceptive method. The important proportion of males who were non-users of contraceptive methods who accepted vasectomy supposed information on contraception to be the most consistent reason; nonetheless, this information was not considered sufficient and timely; thus, adverse economic situation, a certain condition related with the couple such as health or love for the female partner are the more weighty reasons for deciding to accept vasectomy, while the fear of poor sexual performance is the most powerful factor for rejection of vasectomy. Masculine participation in family planning is a factor that conditions contraceptive coverage and its respective benefits. The profile of the male who accepts vasectomy aids in identifying candidates forthe procedure and in reducing unsatisfied demand. Greater diffusion of information of the contraceptive method of vasectomy, greater links between male needs and vasectomy, and maintaining or increasing access to family planning are required.

Advancing environmental risk assessment for transgenic biofeedstock crops

PubMed Central

Wolt, Jeffrey D

2009-01-01

Transgenic modification of plants is a key enabling technology for developing sustainable biofeedstocks for biofuels production. Regulatory decisions and the wider acceptance and development of transgenic biofeedstock crops are considered from the context of science-based risk assessment. The risk assessment paradigm for transgenic biofeedstock crops is fundamentally no different from that of current generation transgenic crops, except that the focus of the assessment must consider the unique attributes of a given biofeedstock crop and its environmental release. For currently envisioned biofeedstock crops, particular emphasis in risk assessment will be given to characterization of altered metabolic profiles and their implications relative to non-target environmental effects and food safety; weediness and invasiveness when plants are modified for abiotic stress tolerance or are domesticated; and aggregate risk when plants are platforms for multi-product production. Robust risk assessments for transgenic biofeedstock crops are case-specific, initiated through problem formulation, and use tiered approaches for risk characterization. PMID:19883509

A novel multiple-stage antimalarial agent that inhibits protein synthesis.

PubMed

Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C S; Norcross, Neil R; Grimaldi, Raffaella; Otto, Thomas D; Proto, William R; Blagborough, Andrew M; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M; Abraham, Tara S; Almeida, Mariana J; Pradhan, Anupam; Porzelle, Achim; Luksch, Torsten; Martínez, María Santos; Luksch, Torsten; Bolscher, Judith M; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M; Churcher, Tom S; Sala, Katarzyna A; Zakutansky, Sara E; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M; Sauerwein, Robert W; Dechering, Koen J; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G; Leroy, Didier; Siegl, Peter; Delves, Michael J; Kyle, Dennis E; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N; Sinden, Robert E; Winzeler, Elizabeth A; Charman, Susan A; Bebrevska, Lidiya; Gray, David W; Campbell, Simon; Fairlamb, Alan H; Willis, Paul A; Rayner, Julian C; Fidock, David A; Read, Kevin D; Gilbert, Ian H

2015-06-18

There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

A stochastic multicriteria model for evidence-based decision making in drug benefit-risk analysis.

PubMed

Tervonen, Tommi; van Valkenhoef, Gert; Buskens, Erik; Hillege, Hans L; Postmus, Douwe

2011-05-30

Drug benefit-risk (BR) analysis is based on firm clinical evidence regarding various safety and efficacy outcomes. In this paper, we propose a new and more formal approach for constructing a supporting multi-criteria model that fully takes into account the evidence on efficacy and adverse drug reactions. Our approach is based on the stochastic multi-criteria acceptability analysis methodology, which allows us to compute the typical value judgments that support a decision, to quantify decision uncertainty, and to compute a comprehensive BR profile. We construct a multi-criteria model for the therapeutic group of second-generation antidepressants. We assess fluoxetine and venlafaxine together with placebo according to incidence of treatment response and three common adverse drug reactions by using data from a published study. Our model shows that there are clear trade-offs among the treatment alternatives. Copyright © 2011 John Wiley & Sons, Ltd.

Applications and challenges of multivalent recombinant vaccines

PubMed Central

Naim, Hussein Y.

2013-01-01

The exceptional discoveries of antigen/gene delivery systems have allowed the development of novel prophylactic and therapeutic vaccine candidates. The vaccine candidates employ various antigen-delivery systems, particularly recombinant viral vectors. Recombinant viral vectors are experimental vaccines similar to DNA vaccines, but they use attenuated viruses or bacterium as a carrier “vector” to introduce microbial DNA to cells of the body. They closely mimic a natural infection and therefore can efficiently stimulate the immune system. Although such recombinant vectors may face extensive preclinical testing and will possibly have to meet stringent regulatory requirements, some of these vectors (e.g. measles virus vectors) may benefit from the profound industrial and clinical experience of the parent vaccine. Most notably, novel vaccines based on live attenuated viruses combine the induction of broad, strong and persistent immune responses with acceptable safety profiles. We assess certain technologies in light of their use against human immunodeficiency virus (HIV). PMID:23249651

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.

PubMed

Popovici-Muller, Janeta; Lemieux, René M; Artin, Erin; Saunders, Jeffrey O; Salituro, Francesco G; Travins, Jeremy; Cianchetta, Giovanni; Cai, Zhenwei; Zhou, Ding; Cui, Dawei; Chen, Ping; Straley, Kimberly; Tobin, Erica; Wang, Fang; David, Muriel D; Penard-Lacronique, Virginie; Quivoron, Cyril; Saada, Véronique; de Botton, Stéphane; Gross, Stefan; Dang, Lenny; Yang, Hua; Utley, Luke; Chen, Yue; Kim, Hyeryun; Jin, Shengfang; Gu, Zhiwei; Yao, Gui; Luo, Zhiyong; Lv, Xiaobing; Fang, Cheng; Yan, Liping; Olaharski, Andrew; Silverman, Lee; Biller, Scott; Su, Shin-San M; Yen, Katharine

2018-04-12

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity.

Retrograde endopyelotomy: a comparison between laser and Acucise balloon cutting catheter.

PubMed

el-Nahas, Ahmed R

2007-03-01

Endopyelotomy and laparoscopic pyeloplasty are the preferred modalities for treatment of ureteropelvic junction obstruction because of their minimally invasive nature. There are continuous efforts for improving endopyelotomy techniques and outcome. Retrograde access represents the natural evolution of endopyelotomy. The Acucise cutting balloon catheter (Applied Medical Resources Corp., Laguna Hills, CA) and ureteroscopic endopyelotomy using holmium laser are the most widely accepted techniques. The Acucise catheter was developed to simplify retrograde endopyelotomy and made it possible for all urologists, regardless of their endourologic skills. The Acucise catheter depends on incision and dilatation of the ureteropelvic junction under fluoroscopic guidance, whereas ureteroscopy allows visual control of the site, depth, and extent of the incision; the holmium laser is a perfect method for a clean precise incision. Review of the English literature showed that the Acucise technique was more widely performed, though laser had better (but not statistically significant) safety and efficacy profiles.

A novel multiple-stage antimalarial agent that inhibits protein synthesis

NASA Astrophysics Data System (ADS)

Baragaña, Beatriz; Hallyburton, Irene; Lee, Marcus C. S.; Norcross, Neil R.; Grimaldi, Raffaella; Otto, Thomas D.; Proto, William R.; Blagborough, Andrew M.; Meister, Stephan; Wirjanata, Grennady; Ruecker, Andrea; Upton, Leanna M.; Abraham, Tara S.; Almeida, Mariana J.; Pradhan, Anupam; Porzelle, Achim; Martínez, María Santos; Bolscher, Judith M.; Woodland, Andrew; Norval, Suzanne; Zuccotto, Fabio; Thomas, John; Simeons, Frederick; Stojanovski, Laste; Osuna-Cabello, Maria; Brock, Paddy M.; Churcher, Tom S.; Sala, Katarzyna A.; Zakutansky, Sara E.; Jiménez-Díaz, María Belén; Sanz, Laura Maria; Riley, Jennifer; Basak, Rajshekhar; Campbell, Michael; Avery, Vicky M.; Sauerwein, Robert W.; Dechering, Koen J.; Noviyanti, Rintis; Campo, Brice; Frearson, Julie A.; Angulo-Barturen, Iñigo; Ferrer-Bazaga, Santiago; Gamo, Francisco Javier; Wyatt, Paul G.; Leroy, Didier; Siegl, Peter; Delves, Michael J.; Kyle, Dennis E.; Wittlin, Sergio; Marfurt, Jutta; Price, Ric N.; Sinden, Robert E.; Winzeler, Elizabeth A.; Charman, Susan A.; Bebrevska, Lidiya; Gray, David W.; Campbell, Simon; Fairlamb, Alan H.; Willis, Paul A.; Rayner, Julian C.; Fidock, David A.; Read, Kevin D.; Gilbert, Ian H.

2015-06-01

There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

A Review of Hepatoprotective Plants Used in Saudi Traditional Medicine

PubMed Central

Al-Asmari, Abdulrahman K.; Al-Elaiwi, Abdulrahman M.; Athar, Md Tanwir; Tariq, Mohammad; Al Eid, Ahmed; Al-Asmary, Saeed M.

2014-01-01

Liver disease is one of the major causes of morbidity and mortality across the world. According to WHO estimates, about 500 million people are living with chronic hepatitis infections resulting in the death of over one million people annually. Medicinal plants serve as a vital source of potentially useful new compounds for the development of effective therapy to combat liver problems. Moreover herbal products have the advantage of better affordability and acceptability, better compatibility with the human body, and minimal side effects and is easier to store. In this review attempt has been made to summarize the scientific data published on hepatoprotective plants used in Saudi Arabian traditional medicine. The information includes medicinal uses of the plants, distribution in Saudi Arabia, ethnopharmacological profile, possible mechanism of action, chemical constituents, and toxicity data. Comprehensive scientific studies on safety and efficacy of these plants can revitalise the treatment of liver diseases. PMID:25587347

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

PubMed Central

2018-01-01

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo. Preliminary data from phase 1 clinical trials enrolling patients with cancers harboring an IDH1 mutation indicate that AG-120 has an acceptable safety profile and clinical activity. PMID:29670690

Is the LINX reflux management system an effective treatment for gastro-oesophageal reflux disease?

PubMed

Loh, Yiwen; McGlone, Emma Rose; Reddy, Marcus; Khan, Omar A

2014-01-01

A best evidence topic in surgery was written according to a structured protocol. The question addressed whether LINX™ Reflux management system is an efficacious treatment for patients with symptoms of gastro-oesophageal reflux disease (GORD) not controlled by proton pump inhibitors (PPI). Forty-eight LINX-related papers were identified using the reported search, of which three represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. All three studies were prospective case studies. They demonstrated that LINX is an efficacious treatment for GORD patients with good short and medium term outcomes and an acceptable safety profile. Further studies are required to determine its long term outcomes and its relative efficacy as compared to other established treatments. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Colorimetric Detection of Plasmodium vivax in Urine Using MSP10 Oligonucleotides and Gold Nanoparticles

PubMed Central

Alnasser, Yossef; Ferradas, Cusi; Clark, Taryn; Calderon, Maritza; Gurbillon, Alejandro; Gamboa, Dionicia; McKakpo, Uri S.; Quakyi, Isabella A.; Bosompem, Kwabena M.; Sullivan, David J.; Vinetz, Joseph M.; Gilman, Robert H.

2016-01-01

Plasmodium vivax is the most prevalent cause of human malaria in the world and can lead to severe disease with high potential for relapse. Its genetic and geographic diversities make it challenging to control. P. vivax is understudied and to achieve control of malaria in endemic areas, a rapid, accurate, and simple diagnostic tool is necessary. In this pilot study, we found that a colorimetric system using AuNPs and MSP10 DNA detection in urine can provide fast, easy, and inexpensive identification of P. vivax. The test exhibited promising sensitivity (84%), high specificity (97%), and only mild cross-reactivity with P. falciparum (21%). It is simple to use, with a visible color change that negates the need for a spectrometer, making it suitable for use in austere conditions. Using urine eliminates the need for finger-prick, increasing both the safety profile and patient acceptance of this model. PMID:27706158

Facial profile esthetics in operated children with bilateral cleft lip and palate

PubMed Central

Lauris, Rita de Cássia Moura Carvalho; Capelozza, Leopoldino; Calil, Louise Resti; Lauris, José Roberto Pereira; Janson, Guilherme; Garib, Daniela Gamba

2017-01-01

ABSTRACT Objective: The aim of this study was to evaluate the facial profile esthetics of rehabilitated children with complete bilateral cleft lip and palate (BCLP), comparing the judgment of professionals related and not related to cleft rehabilitation and laypersons. Methods: Thirty children in the mixed dentition (24 male; 6 female) with a mean age of 7.8 years were evaluated using facial profile photographs by 25 examiners: 5 orthodontists and 5 plastic surgeons with experience in cleft care, 5 orthodontists and 5 plastic surgeons without experience in oral cleft rehabilitation and 5 graduated laymen. Their facial profiles were classified into esthetically unpleasant (grade 1 to 3), esthetically acceptable (grade 4 to 6), and esthetically pleasant (grade 7 to 9). Intraexaminer and interexaminer errors were evaluated using Spearman correlation coefficient and Kendall’s test, respectively. Inter-rater differences were analyzed using Friedman test and Student-Newman-Keuls test for multiple comparisons. Results: Orthodontists dealing with oral clefts rehabilitation considered the majority of the sample as esthetically pleasant. Plastic surgeons of the cleft team and laypersons classified most of the sample as esthetically acceptable. Most of the orthodontists and plastic surgeons not related to cleft care evaluated the facial profile as esthetically unpleasant. The structures associated to unpleasant profiles were the nose, the midface and the upper lip. Conclusions: The facial profile of children with BCLP was classified as esthetically acceptable by laypersons. Professionals related to cleft rehabilitation were more lenient and those not related to cleft care were stricter to facial esthetics than laypersons. PMID:28902248

Shapes of star-gas waves in spiral galaxies

NASA Technical Reports Server (NTRS)

Lubow, Stephen H.

1988-01-01

Density-wave profile shapes are influenced by several effects. By solving viscous fluid equations, the nonlinear effects of the gas and its gravitational interaction with the stars can be analyzed. The stars are treated through a linear theory developed by Lin and coworkers. Short wavelength gravitational forces are important in determining the gas density profile shape. With the inclusion of disk finite thickness effects, the gas gravitational field remains important, but is significantly reduced at short wavelengths. Softening of the gas equation of state results in an enhanced response and a smoothing of the gas density profile. A Newtonian stress relation is marginally acceptable for HI gas clouds, but not acceptable for giant molecular clouds.

Sensory profile and acceptability for pitanga (Eugenia uniflora L.) nectar with different sweeteners.

PubMed

Freitas, Mírian Luisa Faria; Dutra, Mariana Borges de Lima; Bolini, Helena Maria André

2016-12-01

The objective of this study was to evaluate the sensory properties and acceptability of pitanga nectar samples prepared with sucrose and different sweeteners (sucralose, aspartame, stevia with 40% rebaudioside A, stevia with 95% rebaudioside A, neotame, and a 2:1 cyclamate/saccharin blend). A total of 13 assessors participated in a quantitative descriptive analysis and evaluated the samples in relation to the descriptor terms. The acceptability test was carried out by 120 fruit juice consumers. The results of the quantitative descriptive analysis of pitanga nectar showed that samples prepared with sucralose, aspartame, and the 2:1 cyclamate/saccharin blend had sensory profiles similar to that of the sample prepared with sucrose. Consumers' most accepted samples were prepared with sucrose, sucralose, aspartame, and neotame. The sweeteners that have the greatest potential to replace sucrose in pitanga nectar are sucralose and aspartame. © The Author(s) 2016.

Mindful Application of Aviation Practices in Healthcare.

PubMed

Powell-Dunford, Nicole; Brennan, Peter A; Peerally, Mohammad Farhad; Kapur, Narinder; Hynes, Jonny M; Hodkinson, Peter D

2017-12-01

Evidence supports the efficacy of incorporating select recognized aviation practices and procedures into healthcare. Incident analysis, debrief, safety brief, and crew resource management (CRM) have all been assessed for implementation within the UK healthcare system, a world leader in aviation-based patient safety initiatives. Mindful application, in which aviation practices are specifically tailored to the unique healthcare setting, show promise in terms of acceptance and long-term sustainment. In order to establish British healthcare applications of aviation practices, a PubMed search of UK authored manuscripts published between 2005-2016 was undertaken using search terms 'aviation,' 'healthcare,' 'checklist,' and 'CRM.' A convenience sample of UK-authored aviation medical conference presentations and UK-authored patient safety manuscripts were also reviewed. A total of 11 of 94 papers with UK academic affiliations published between 2005-2016 and relevant to aviation modeled healthcare delivery were found. The debrief process, incident analysis, and CRM are the primary practices incorporated into UK healthcare, with success dependent on cultural acceptance and mindful application. CRM training has gained significant acceptance in UK healthcare environments. Aviation modeled incident analysis, debrief, safety brief, and CRM training are increasingly undertaken within the UK healthcare system. Nuanced application, in which the unique aspects of the healthcare setting are addressed as part of a comprehensive safety approach, shows promise for long-term success. The patient safety brief and aviation modeled incident analysis are in earlier phases of implementation, and warrant further analysis.Powell-Dunford N, Brennan PA, Peerally MF, Kapur N, Hynes JM, Hodkinson PD. Mindful application of aviation practices in healthcare. Aerosp Med Hum Perform. 2017; 88(12):1107-1116.

Semi-Markov Approach to the Shipping Safety Modelling

NASA Astrophysics Data System (ADS)

Guze, Sambor; Smolarek, Leszek

2012-02-01

In the paper the navigational safety model of a ship on the open area has been studied under conditions of incomplete information. Moreover the structure of semi-Markov processes is used to analyse the stochastic ship safety according to the subjective acceptance of risk by the navigator. In addition, the navigator’s behaviour can be analysed by using the numerical simulation to estimate the probability of collision in the safety model.

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.

A brief, trauma-informed intervention increases safety behavior and reduces HIV risk for drug-involved women who trade sex.

PubMed

Decker, Michele R; Tomko, Catherine; Wingo, Erin; Sawyer, Anne; Peitzmeier, Sarah; Glass, Nancy; Sherman, Susan G

2017-08-01

Female sex workers (FSWs) are an important population for HIV acquisition and transmission. Their risks are shaped by behavioral, sexual network, and structural level factors. Violence is pervasive and associated with HIV risk behavior and infection, yet interventions to address the dual epidemics of violence and HIV among FSWs are limited. We used participatory methods to develop a brief, trauma-informed intervention, INSPIRE (Integrating Safety Promotion with HIV Risk Reduction), to improve safety and reduce HIV risk for FSWs. A quasi-experimental, single group pretest-posttest study evaluated intervention feasibility, acceptability and efficacy among FSWs in Baltimore, MD, most of whom were drug-involved (baseline n = 60; follow-up n = 39 [65%]; non-differential by demographics or outcomes). Qualitative data collected at follow-up contextualizes findings. Based on community partnership and FSW input, emergent goals included violence-related support, connection with services, and buffering against structural forces that blame FSWs for violence. Qualitative and quantitative results demonstrate feasibility and acceptability. At follow-up, improvements were seen in avoidance of client condom negotiation (p = 0.04), and frequency of sex trade under the influence of drugs or alcohol (p = 0.04). Women's safety behavior increased (p < 0.001). Participants improved knowledge and use of sexual violence support (p < 0.01) and use of intimate partner violence support (p < 0.01). By follow-up, most respondents (68.4%) knew at least one program to obtain assistance reporting violence to police. Over the short follow-up period, client violence increased. In reflecting on intervention acceptability, participants emphasized the value of a safe and supportive space to discuss violence. This brief, trauma-informed intervention was feasible and highly acceptable to FSWs. It prompted safety behavior, mitigated sex trade under the influence, and bolstered confidence in condom negotiation. INSPIRE influenced endpoints deemed valuable by community partners, specifically improving connection to support services and building confidence in the face of myths that falsely blame sex workers for violence. Violence persisted; prevention also requires targeting perpetrators, and longer follow-up durations as women acquire safety skills. This pilot study informs scalable interventions that address trauma and its impact on HIV acquisition and care trajectories for FSWs. Addressing violence in the context of HIV prevention is feasible, acceptable to FSWs, and can improve safety and reduce HIV risk, thus supporting FSW health and human rights.

Recent RF Experiments and Application of RF Waves to Real-Time Control of Safety Factor Profile in JT-60U

NASA Astrophysics Data System (ADS)

Suzuki, T.; Isayama, A.; Ide, S.; Fujita, T.; Oikawa, T.; Sakata, S.; Sueoka, M.; Hosoyama, H.; JT-60 Team

2005-09-01

Two topics of applications of RF waves to current profile control in JT-60U are presented; application of lower-hybrid (LH) waves to safety factor profile control and electron cyclotron (EC) waves to neo-classical tearing mode (NTM) control. A real-time control system of safety factor (q) profile was developed. This system, for the first time, enables 1) real time evaluation of q profile using local magnetic pitch angle measurement by motional Stark effect (MSE) diagnostic and 2) control of current drive (CD) location (ρCD) by controlling the parallel refractive index N∥ of LH waves through control of phase difference (Δφ) of LH waves between multi-junction launcher modules. The method for real-time q profile evaluation was newly developed, without time-consuming reconstruction of equilibrium, so that the method requires less computational time. Safety factor profile by the real-time calculation agrees well with that by equilibrium reconstruction with MSE. The control system controls ρCD through Δφ in such a way to decrease the largest residual between the real-time evaluated q profile q(r) and its reference profile qref(r). The real-time control system was applied to a positive shear plasma (q(0)˜1). The reference q profile was set to monotonic positive shear profile having qref(0)=1.3. The real-time q profile approached to the qref(r) during application of real-time control, and was sustained for 3s, which was limited by the duration of the injected LH power. Temporal evolution of current profile was consistent with relaxation of inductive electric field induced by theoretical LH driven current. An m/n=3/2 NTM that appeared at βN˜3 was completely stabilized by ECCD applied to a fully-developed NTM. Precise ECCD at NTM island was essential for the stabilization. ECCD that was applied to resonant rational surface (q=3/2) before an NTM onset suppressed appearance of NTM. In order to keep NTM intensity below a level, ECCD before the mode onset was more effective than that after mode saturation.

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.

Connected vehicle pilot - privacy white paper.

DOT National Transportation Integrated Search

2016-09-21

Connected Vehicle (CV) technologies is beneficial when users feel safe in broadcasting their Basic Safety Message and trust in their safety and mobility applications. Users must also accept and have a right to know how their privacy is impacted by be...

Alternative food safety intervention technologies: flash pasteurization of finfish

USDA-ARS?s Scientific Manuscript database

Alternative nonthermal and thermal food safety interventions are gaining acceptance by the food processing industry and consumers. These technologies include high pressure processing, ultraviolet and pulsed light, ionizing radiation, pulsed and radiofrequency electric fields, cold atmospheric plasm...

A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK.

PubMed

Marlow, Robin; Kuriyakose, Sherine; Mesaros, Narcisa; Han, Htay Htay; Tomlinson, Richard; Faust, Saul N; Snape, Matthew D; Pollard, Andrew J; Finn, Adam

2018-04-19

To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV B ) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV). This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV B or dTap-IPV R ) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated. 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV B group and 130 in the dTap-IPV R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV B group. Non-inferiority of dTap-IPV B to dTap-IPV R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old. NCT01245049 (ClinicalTrials.gov). Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Autonomous rehabilitation at stroke patients home for balance and gait: safety, usability and compliance of a virtual reality system.

PubMed

Held, Jeremia P; Ferrer, Begoña; Mainetti, Renato; Steblin, Alexander; Hertler, Benjamin; Moreno-Conde, Alberto; Dueñas, Alvaro; Pajaro, Marta; L-Parra-Calderón, Carlos; Vargiu, Eloisa; Zarco, Maria J; Barrera, Maria; Echevarria, Carmen; Jódar-Sánchez, Francisco; Luft, Andreas R; Borghese, Nunzio A

2017-09-25

New technologies, such as telerehabilitation and gaming devices offer the possibility for patients to train at home. This opens the challenge of safety for the patient as he is called to exercise neither with a therapist on the patients' side nor with a therapist linked remotely to supervise the sessions. To study the safety, usability and patient acceptance of an autonomous telerehabilitation system for balance and gait (the REWIRE platform) in the patients home. Cohort study. Community, in the stroke patients' home. 15 participants with first-ever stroke, with a mild to moderate residual deficit of the lower extremities. Autonomous rehabilitation based on virtual rehabilitation was provided at the participants' home for twelve weeks. The primary outcome was compliance (the ratio between days of actual and scheduled training), analysed with the two-tailed Wilcoxon Mann- Whitney test. Furthermore safety is defined by adverse events. The secondary endpoint was the acceptance of the system measured with the Technology Acceptance Model. Additionally, the cumulative duration of weekly training was analysed. During the study there were no adverse events related to the therapy. Patients performed on average 71% (range 39 to 92%) of the scheduled sessions. The Technology Acceptance Model Questionnaire showed excellent values for stroke patients after the training. The average training duration per week was 99 ±53min. Autonomous telerehabilitation for balance and gait training with the REWIRE-system is safe, feasible and can help to intensive rehabilitative therapy at home. Telerehabilitation enables safe training in home environment and supports of the standard rehabilitation therapy.

Introduction into the NHS of magnetic sphincter augmentation: an innovative surgical therapy for reflux - results and challenges.

PubMed

Prakash, D; Campbell, B; Wajed, S

2018-04-01

Introduction Gastro-oesophageal reflux disease (GORD) is a common, chronic debilitating condition. Surgical management traditionally involves fundoplication. Magnetic sphincter augmentation (MSA) is a new definitive treatment. We describe our experience of introducing this innovative therapy into NHS practice and report the early clinical outcomes. Methods MSA was introduced into NHS practice following successful acceptance of a cost-effective business plan and close observation of National Institute for Health and Care Excellence (NICE) recommendations for new procedures, including a carefully planned prospective data collection over a two-year follow-up period. Results Forty-seven patients underwent MSA over the 40-month period. Reflux health-related quality of life (GERD-HRQL) was significantly improved after the procedure and maintained at one- and two-year (P < 0.0001) follow-up. Drug dependency went from 100% at baseline to 2.6% and 8.7% after one and two years. High levels of patient satisfaction were reported. There were no adverse events. Conclusions MSA is highly effective in the treatment of uncomplicated GORD, with durable results and an excellent safety profile. This laparoscopic, minimally invasive procedure provides a good alternative for patients where surgical anatomy is unaltered. Our experience demonstrates that innovative technology can be incorporated into NHS practice with an acceptable business plan and compliance with NICE recommendations.

Nomegestrol acetate/17-beta estradiol: a review of efficacy, safety, and patient acceptability

PubMed Central

Akintomide, Hannat; Panicker, Sabeena

2015-01-01

Nomegestrol acetate (NOMAC) 2.5 mg with 17-beta estradiol (E2) 1.5 mg is a new combined oral contraceptive (COC) formulation and is the first monophasic E2 pill to be marketed, having been licensed for use in Europe in 2011. It is available to be taken daily in a regimen of 24 active pills followed by four placebo pills. NOMAC is a highly selective 19-nor progestogen derivative with specific binding to progesterone receptors, anti-estrogenic activity and no androgenic, mineralocorticoid nor glucocorticoid effects. E2 is an estrogen that is identical to endogenous estrogen. While it has been in use for only a short period of time, current evidence suggests that NOMAC/E2 is just as effective, safe, and acceptable as existing COC preparations. Two large Phase III trials conducted in the Americas and across Europe, Australia, and Asia showed lower cumulative pregnancy rates in the NOMAC/E2 groups compared to the drospirenone (DRSP) 3 mg in combination with ethinyl estradiol (EE) 30 µg (DRSP/EE) groups but this difference was not statistically significant. NOMAC/E2 exhibits a good safety profile and has less effects on cardiovascular risk, hemostatic, metabolic, and endocrine factors in comparison to COCs containing EE in combination with levonorgestrel (LNG) or DRSP. NOMAC/E2 has also been found to cause less breast cell proliferation when compared to E2 alone and has some anti-proliferative effect on human breast cancer cells. NOMAC/E2 is considered acceptable as its compliance, continuation rates, and bleeding patterns were similar to COCs containing DRSP/EE and LNG 150 µg combined with EE 30 µg or LNG 100 µg combined with EE 20 µg (LNG/EE). However, discontinuation was found to be slightly higher in the NOMAC/E2 groups in the two large Phase III trials comparing NOMAC/E2 use with DRSP/EE. As the scientific literature has limited information on NOMAC/E2, further experience with NOMAC/E2 is required. PMID:29386925

Field test of a motorcycle safety education course for novice riders

DOT National Transportation Integrated Search

1982-07-01

The purpose of this study was to subject the Motorcycle Safety Foundation's Motorcycle Rider Course (MRC) to a large-scale field test designed to evaluate the following aspects of the course: (1) Instructional Effectiveness, (2) User Acceptance, and ...

Guidelines for the acceptance of peroxide-containing oral hygiene products. American Dental Association Council on Dental Therapeutics.

PubMed

1994-08-01

Safety and efficacy criteria are defined for oral products containing various forms of peroxides. The guidelines ask for safety and efficacy studies plus observation criteria that include long-term follow-up.

Analysis of existing work-zone devices with MASH safety performance criteria.

DOT National Transportation Integrated Search

2009-02-01

Crashworthy, work-zone, portable sign support systems accepted under NCHRP Report No. 350 were analyzed to : predict their safety peformance according to the TL-3 MASH evaluation criteria. An analysis was conducted to determine : which hardware param...

40 CFR 68.65 - Process safety information.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.65 Process safety... data; (4) Reactivity data: (5) Corrosivity data; (6) Thermal and chemical stability data; and (7... operator shall document that equipment complies with recognized and generally accepted good engineering...

Development and validation of nonthermal and advanced thermal food safety intervention technologies

USDA-ARS?s Scientific Manuscript database

Alternative nonthermal and thermal food safety interventions are gaining acceptance by the food processing industry and consumers. These technologies include high pressure processing, ultraviolet and pulsed light, ionizing radiation, pulsed and radiofrequency electric fields, cold atmospheric plasm...

21 CFR 123.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... acceptable levels. (c) Critical limit means the maximum or minimum value to which a physical, biological, or... acceptable level the occurrence of the identified food safety hazard. (d) Fish means fresh or saltwater... used to indicate conditions during processing at a critical control point. (k)(1) Processing means...

47 CFR 80.43 - Equipment acceptable for licensing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Equipment acceptable for licensing. 80.43 Section 80.43 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO... are used on vessels in the Maritime Security Fleet and are deemed to satisfy all Commission equipment...

47 CFR 80.43 - Equipment acceptable for licensing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Equipment acceptable for licensing. 80.43 Section 80.43 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO... are used on vessels in the Maritime Security Fleet and are deemed to satisfy all Commission equipment...

Safety and Acceptability of Couples HIV Testing and Counseling for US Men Who Have Sex with Men: A Randomized Prevention Study

PubMed Central

Sullivan, Patrick S.; White, Darcy; Rosenberg, Eli S.; Barnes, Jasper; Jones, Jeb; Dasgupta, Sharoda; O’Hara, Brandon; Scales, Lamont; Salazar, Laura F.; Wingood, Gina; DiClemente, Ralph; Wall, Kristin M.; Hoff, Colleen; Gratzer, Beau; Allen, Susan; Stephenson, Rob

2013-01-01

We tested a couples HIV testing and counseling (CHTC) intervention with male couples in Atlanta by randomizing eligible couples to receive either CHTC or separate individual voluntary HIV counseling and testing (iVCT). To evaluate the acceptability and safety of CHTC, main outcomes were satisfaction with the intervention and the proportions of couples reporting intimate partner violence (IPV) and relationship dissolution after the service. The results indicated that the service was very acceptable to men (median 7-item index of satisfaction was 34 for CHTC and 35 for iVCT, P = .4). There was no difference in either incident IPV (22% versus 17% for CHTC and iVCT, respectively, P = .6) or relationship dissolution (42% versus 51% for CHTC and iVCT, respectively, P = .5). Based on the preliminary data, CHTC is safe for male couples, and it is equally acceptable to iVCT for men who have main partners. PMID:23995295

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

PubMed

Chlibek, Roman; Bayas, José M; Collins, Harry; de la Pinta, Maria Luisa Rodriguez; Ledent, Edouard; Mols, Johann F; Heineman, Thomas C

2013-12-15

An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. NCT00802464.

Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability.

PubMed

Cho, Hee Ju; Yoo, Tag Keun

2014-01-01

α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society.

Silodosin for the treatment of clinical benign prostatic hyperplasia: safety, efficacy, and patient acceptability

PubMed Central

Cho, Hee Ju; Yoo, Tag Keun

2014-01-01

α1-Adrenergic receptor antagonists are commonly used to treat male lower urinary tract symptoms and benign prostatic hyperplasia (BPH). We performed a literature search using PubMed, Medline via Ovid, Embase, and the Cochrane Library databases to identify studies on the treatment of BPH by silodosin. Silodosin is a novel α1-adrenergic receptor antagonist whose affinity for the α1A-adrenergic receptor is greater than that for the α1B-adrenergic receptor. Therefore, silodosin does not increase the incidence of blood pressure-related side effects, which may result from the inhibition of the α1B-adrenergic receptor. Patients receiving silodosin at a daily dose of 8 mg showed a significant improvement in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving a placebo. Silodosin also improved both storage and voiding symptoms, indicating that silodosin is effective, even during early phases of BPH treatment. Follow-up extension studies performed in the United States, Europe, and Asia demonstrated its long-term safety and efficacy. In the European study, silodosin significantly reduced nocturia compared to the placebo. Although retrograde or abnormal ejaculation was the most commonly reported symptom in these studies, only a few patients discontinued treatment. The incidence of adverse cardiovascular events was also very low. Evidence showing solid efficacy and cardiovascular safety profiles of silodosin will provide a good solution for the treatment of lower urinary tract symptoms associated with BPH in an increasingly aging society. PMID:25328864

A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia).

PubMed

Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

2017-01-01

Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed ( Ambrosia artemisiifolia ) is on the rise throughout Europe, having a significant negative impact on the patients' and their family's quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.

A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia)

PubMed Central

Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

2017-01-01

Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients’ and their family’s quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success. PMID:28243068

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting.

PubMed

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem; Bollaerts, Anne; Demoitie, Marie-Ange; Kany Luabeya, Angelique Kany; De Ruymaeker, Evi; Tameris, Michele; Lapierre, Didier; Scriba, Thomas J

2015-07-31

Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting

PubMed Central

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L.; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem

2018-01-01

Background Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. Methods In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. Results No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. Conclusions The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. PMID:26072017

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.

In Vitro and in Vivo Characterization of MOD-4023, a Long-Acting Carboxy-Terminal Peptide (CTP)-Modified Human Growth Hormone.

PubMed

Hershkovitz, Oren; Bar-Ilan, Ahuva; Guy, Rachel; Felikman, Yana; Moschcovich, Laura; Hwa, Vivian; Rosenfeld, Ron G; Fima, Eyal; Hart, Gili

2016-02-01

MOD-4023 is a novel long-acting version of human growth hormone (hGH), containing the carboxy-terminal peptide (CTP) of human chorionic gonadotropin (hCG). MOD-4023 is being developed as a treatment for adults and children with growth hormone deficiency (GHD), which would require fewer injections than currently available GH formulations and thus reduce patient discomfort and increase compliance. This study characterizes MOD-4023's binding affinities for the growth hormone receptor, as well as the pharmacokinetic and pharmacodynamics, toxicology, and safety profiles of repeated dosing of MOD-4023 in Sprague-Dawley rats and Rhesus monkeys. Although MOD-4023 exhibited reduced in vitro potency and lower affinity to the GH receptor than recombinant hGH (rhGH), administration of MOD-4023 every 5 days in rats and monkeys resulted in exposure comparable to daily rhGH, and the serum half-life of MOD-4023 was significantly longer. Repeated administration of MOD-4023 led to elevated levels of insulin-like growth factor 1 (IGF-1), and twice-weekly injections of MOD-4023 resulted in larger increase in weight gain with fewer injections and a lower accumulative hGH dose. Thus, the increased half-life of MOD-4023 in comparison to hGH may increase the frequency of protein-receptor interactions and compensate for its decreased in vitro potency. MOD-4023 was found to be well-tolerated in rats and monkeys, with minimal adverse events, suggesting an acceptable safety profile. These results provide a basis for the continued clinical development of MOD-4023 as a novel treatment of GHD in children and adults.

Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

PubMed

Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

2018-01-01

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Pharmacokinetic Profile and Palatability of Atomoxetine Oral Solution in Healthy Japanese Male Adults.

PubMed

Nakano, Masako; Witcher, Jennifer; Satoi, Yoichi; Goto, Taro

2016-11-01

There is a clinical need for a liquid formulation of atomoxetine. We assessed the safety and bioequivalence of an atomoxetine oral solution. This was an open-label, randomized, crossover study. Healthy adult male Japanese subjects (n = 42) with a cytochrome P450 2D6 extensive (including intermediate and ultrarapid) metabolizer genotype were administered atomoxetine 50 mg as oral solution and capsules once each, with a washout period >5 days between doses. Blood samples were used to analyze pharmacokinetic parameters, particularly maximum observed drug concentration (C max ) and area under the concentration vs. time curve from time zero to the last time point with a measurable concentration (AUC 0-last ). Bioequivalence was concluded if the 90 % confidence interval of the ratio of geometric means between formulations for both C max and AUC 0-last were within the interval of 0.8-1.25. Safety assessments included determination of adverse events. Taste was evaluated via a five-item questionnaire immediately and 10 min after taking atomoxetine oral solution. Forty subjects completed the study. Plasma concentration-time profiles of atomoxetine oral solution and capsules were similar, and the statistical analysis of systemic exposure showed that the two formulations were bioequivalent. Adverse events were mild and similar in type and frequency between the formulations. For taste acceptability, only 7.1 % of subjects responded that the oral solution would be difficult to take every day. Atomoxetine oral solution is bioequivalent to atomoxetine capsules and potentially fulfills the need for an oral solution atomoxetine formulation that will facilitate treatment of children with attention-deficit hyperactivity disorder.

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers.

PubMed

Rice, David; Heil, Justin W; Biernat, Lukasz

2017-03-01

Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max ) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. NCT02210247.

Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis.

PubMed

Richeldi, Luca; Cottin, Vincent; Flaherty, Kevin R; Kolb, Martin; Inoue, Yoshikazu; Raghu, Ganesh; Taniguchi, Hiroyuki; Hansell, David M; Nicholson, Andrew G; Le Maulf, Florence; Stowasser, Susanne; Collard, Harold R

2014-07-01

Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF). Data from the Phase II TOMORROW study suggested that nintedanib 150 mg twice daily had clinical benefits with an acceptable safety profile. The INPULSIS™ trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150 mg twice daily with placebo in patients with IPF. Eligible patients were aged ≥40 years with a diagnosis of IPF within 5 years before randomization who had undergone a chest high-resolution computed tomography (HRCT) scan within 1-year before screening, and who had a forced vital capacity (FVC) of ≥50% predicted and a diffusing capacity for carbon monoxide of 30-79% predicted. Participants were randomized 3:2 to receive nintedanib or placebo for 52 weeks. The primary endpoint is the annual rate of decline in FVC. The key secondary endpoints are change from baseline in the total score on the St. George's Respiratory Questionnaire (a measure of health-related quality of life) over 52 weeks and time to first acute exacerbation. Enrolment of 1066 patients in 24 countries was completed in September 2012. Results will be reported in the first half of 2014. The INPULSIS™ trials will determine the efficacy of nintedanib in patients with IPF, including its impact on disease progression as defined by decline in FVC, acute exacerbations and health-related quality of life. In addition, they will characterise the adverse event profile of nintedanib in this patient population. Registered at ClinicalTrials.gov (identifiers: NCT01335464 and NCT01335477). Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

First-Principles-Driven Model-Based Optimal Control of the Current Profile in NSTX-U

NASA Astrophysics Data System (ADS)

Ilhan, Zeki; Barton, Justin; Wehner, William; Schuster, Eugenio; Gates, David; Gerhardt, Stefan; Kolemen, Egemen; Menard, Jonathan

2014-10-01

Regulation in time of the toroidal current profile is one of the main challenges toward the realization of the next-step operational goals for NSTX-U. A nonlinear, control-oriented, physics-based model describing the temporal evolution of the current profile is obtained by combining the magnetic diffusion equation with empirical correlations obtained at NSTX-U for the electron density, electron temperature, and non-inductive current drives. In this work, the proposed model is embedded into the control design process to synthesize a time-variant, linear-quadratic-integral, optimal controller capable of regulating the safety factor profile around a desired target profile while rejecting disturbances. Neutral beam injectors and the total plasma current are used as actuators to shape the current profile. The effectiveness of the proposed controller in regulating the safety factor profile in NSTX-U is demonstrated via closed-loop predictive simulations carried out in PTRANSP. Supported by PPPL.

Neural network evaluation of tokamak current profiles for real time control

NASA Astrophysics Data System (ADS)

Wróblewski, Dariusz

1997-02-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q0, minimum value of q, qmin, and the location of qmin. Very good performance of the trained neural network both for simulated test data and for experimental datais demonstrated.

Neural network evaluation of tokamak current profiles for real time control (abstract)

NASA Astrophysics Data System (ADS)

Wróblewski, Dariusz

1997-01-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q0, minimum value of q, qmin, and the location of qmin. Very good performance of the trained neural network both for simulated test data and for experimental data is demonstrated.

Food Safety Education Using an Interactive Multimedia Kiosk in a WIC Setting: Correlates of Client Satisfaction and Practical Issues

ERIC Educational Resources Information Center

Trepka, Mary Jo; Newman, Frederick L.; Huffman, Fatma G.; Dixon, Zisca

2010-01-01

Objective: To assess acceptability of food safety education delivered by interactive multimedia (IMM) in a Supplemental Nutrition Program for Women, Infants and Children Program (WIC) clinic. Methods: Female clients or caregivers (n = 176) completed the food-handling survey; then an IMM food safety education program on a computer kiosk.…

77 FR 24992 - OSHA Strategic Partnership Program for Worker Safety and Health (OSPP); Extension of the Office...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... Strategic Partnership Program for Worker Safety and Health (OSPP); Extension of the Office of Management and... specified in the OSHAs Strategic Partnership Program for Worker Safety and Health (OSPP). DATES: Comments... accepted during the Department of Labor's and Docket Office's normal business hours, 8:15 a.m. to 4:45 p.m...

Nurses' experiences and perspectives on medication safety practices: an explorative qualitative study.

PubMed

Smeulers, Marian; Onderwater, Astrid T; van Zwieten, Myra C B; Vermeulen, Hester

2014-04-01

To explore nurses' experiences with and perspectives on preventing medication administration errors. Insight into nurses' experiences with and perspectives on preventing medication administration errors is important and can be utilised to tailor and implement safety practices. A qualitative interview study of 20 nurses in an academic medical centre was conducted between March and December of 2011. Three themes emerged from this study: (1) nurses' roles and responsibilities in medication safety: aside from safe preparation and administration, the clinical reasoning of nurses is essential for medication safety; (2) nurses' ability to work safely: knowledge of risks and nurses' work circumstances influence their ability to work safely; and (3) nurses' acceptance of safety practices: advantages, feasibility and appropriateness are important incentives for acceptance of a safety practice. Nurses' experiences coincide with the assumption that they are in a pre-eminent position to enable safe medication management; however, their ability to adequately perform this role depends on sufficient knowledge to assess the risks of medication administration and on the circumstances in which they work. Safe medication management requires a learning climate and professional practice environment that enables further development of professional nursing skills and knowledge. © 2014 John Wiley & Sons Ltd.

Development of a cross-over randomized trial method to determine the acceptability and safety of novel ready-to-use therapeutic foods.

PubMed

Dibari, Filippo; Bahwere, Paluku; Huerga, Helena; Irena, Abel Hailu; Owino, Victor; Collins, Steve; Seal, Andrew

2013-01-01

To develop a method for determining the acceptability and safety of ready-to-use therapeutic foods (RUTF) before clinical trialing. Acceptability was defined using a combination of three consumption, nine safety, and six preference criteria. These were used to compare a soy/maize/sorghum RUTF (SMS-RUTFh), designed for the rehabilitation of human immunodeficiency virus/tuberculosis (HIV/TB) wasted adults, with a peanut-butter/milk-powder paste (P-RUTF; brand: Plumpy'nut) designed for pediatric treatment. A cross-over, randomized, controlled trial was conducted in Kenya. Ten days of repeated measures of product intake by 41 HIV/TB patients, >18 y old, body mass index (BMI) 18-24 kg · m(-2), 250 g were offered daily under direct observation as a replacement lunch meal. Consumption, comorbidity, and preferences were recorded. The study arms had similar age, sex, marital status, initial BMI, and middle upper-arm circumference. No carryover effect or serious adverse events were found. SMS-RUTFh energy intake was not statistically different from the control, when adjusted for BMI on day 1, and the presence of throat sores. General preference, taste, and sweetness scores were higher for SMS-RUTFh compared to the control (P < 0.05). Most consumption, safety, and preference criteria for SMS-RUTFh were satisfied except for the average number of days of nausea (0.16 versus 0.09 d) and vomiting (0.04 versus 0.02 d), which occurred with a higher frequency (P < 0.05). SMS-RUTFh appears to be acceptable and can be safely clinically trialed, if close monitoring of vomiting and nausea is included. The method reported here is a useful and feasible approach for testing the acceptability of ready-to-use foods in low income countries. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of simulation in mixed-methods research: a framework & application to patient safety.

PubMed

Guise, Jeanne-Marie; Hansen, Matthew; Lambert, William; O'Brien, Kerth

2017-05-04

Research in patient safety is an important area of health services research and is a national priority. It is challenging to investigate rare occurrences, explore potential causes, and account for the complex, dynamic context of healthcare - yet all are required in patient safety research. Simulation technologies have become widely accepted as education and clinical tools, but have yet to become a standard tool for research. We developed a framework for research that integrates accepted patient safety models with mixed-methods research approaches and describe the performance of the framework in a working example of a large National Institutes of Health (NIH)-funded R01 investigation. This worked example of a framework in action, identifies the strengths and limitations of qualitative and quantitative research approaches commonly used in health services research. Each approach builds essential layers of knowledge. We describe how the use of simulation ties these layers of knowledge together and adds new and unique dimensions of knowledge. A mixed-methods research approach that includes simulation provides a broad multi-dimensional approach to health services and patient safety research.

Exuberant and inhibited children: Person-centered profiles and links to social adjustment.

PubMed

Dollar, Jessica M; Stifter, Cynthia A; Buss, Kristin A

2017-07-01

The current study aimed to substantiate and extend our understanding regarding the existence and developmental pathways of 3 distinct temperament profiles-exuberant, inhibited, and average approach-in a sample of 3.5-year-old children (n = 121). The interactions between temperamental styles and specific types of effortful control, inhibitory control and attentional control, were also examined in predicting kindergarten peer acceptance. Latent profile analysis identified 3 temperamental styles: exuberant, inhibited, and average approach. Support was found for the adaptive role of inhibitory control for exuberant children and attentional control for inhibited children in promoting peer acceptance in kindergarten. These findings add to our current understanding of temperamental profiles by using sophisticated methodology in a slightly older, community sample, as well as the importance of examining specific types of self-regulation to identify which skills lower risk for children of different temperamental styles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

75 FR 43495 - Sunshine Act Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... DEFENSE NUCLEAR FACILITIES SAFETY BOARD Sunshine Act Notice AGENCY: Defense Nuclear Facilities..., structures, and components, and (5) safety-related design aspects of new facilities or modifications of existing facilities needed to deliver high-level waste feed. The Board will be prepared to accept any other...

14 CFR 415.35 - Acceptable flight risk.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Acceptable flight risk. 415.35 Section 415.35 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT... collective members of the public exposed to debris hazards from any one launch. To obtain safety approval, an...

14 CFR 415.35 - Acceptable flight risk.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Acceptable flight risk. 415.35 Section 415.35 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT... collective members of the public exposed to debris hazards from any one launch. To obtain safety approval, an...

14 CFR 415.35 - Acceptable flight risk.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Acceptable flight risk. 415.35 Section 415.35 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT... collective members of the public exposed to debris hazards from any one launch. To obtain safety approval, an...

14 CFR 415.35 - Acceptable flight risk.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Acceptable flight risk. 415.35 Section 415.35 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT... collective members of the public exposed to debris hazards from any one launch. To obtain safety approval, an...

37 CFR 1.803 - Acceptable depository.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Biological Material § 1.803 Acceptable depository. (a) A deposit shall be recognized for the purposes of... depository must: (i) Have a continuous existence; (ii) Exist independent of the control of the depositor... safety measures to minimize the risk of losing biological material deposited with it; (v) Be impartial...

37 CFR 1.803 - Acceptable depository.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Biological Material § 1.803 Acceptable depository. (a) A deposit shall be recognized for the purposes of... depository must: (i) Have a continuous existence; (ii) Exist independent of the control of the depositor... safety measures to minimize the risk of losing biological material deposited with it; (v) Be impartial...

37 CFR 1.803 - Acceptable depository.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Biological Material § 1.803 Acceptable depository. (a) A deposit shall be recognized for the purposes of... depository must: (i) Have a continuous existence; (ii) Exist independent of the control of the depositor... safety measures to minimize the risk of losing biological material deposited with it; (v) Be impartial...

76 FR 49751 - Perfect Fitness, Provisional Acceptance of a Settlement Agreement and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

... CONSUMER PRODUCT SAFETY COMMISSION [CPSC Docket No. 11-C0009] Perfect Fitness, Provisional...(e). Published below is a provisionally-accepted Settlement Agreement with Perfect Fitness... accordance with 16 CFR 1118.20, Perfect Fitness and staff (``Staff'') of the United States Consumer Product...

14 CFR 415.35 - Acceptable flight risk.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Acceptable flight risk. 415.35 Section 415.35 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT... collective members of the public exposed to debris hazards from any one launch. To obtain safety approval, an...

A Systematic Review Comparing the Acceptability, Validity and Concordance of Discrete Choice Experiments and Best-Worst Scaling for Eliciting Preferences in Healthcare.

PubMed

Whitty, Jennifer A; Oliveira Gonçalves, Ana Sofia

2018-06-01

The aim of this study was to compare the acceptability, validity and concordance of discrete choice experiment (DCE) and best-worst scaling (BWS) stated preference approaches in health. A systematic search of EMBASE, Medline, AMED, PubMed, CINAHL, Cochrane Library and EconLit databases was undertaken in October to December 2016 without date restriction. Studies were included if they were published in English, presented empirical data related to the administration or findings of traditional format DCE and object-, profile- or multiprofile-case BWS, and were related to health. Study quality was assessed using the PREFS checklist. Fourteen articles describing 12 studies were included, comparing DCE with profile-case BWS (9 studies), DCE and multiprofile-case BWS (1 study), and profile- and multiprofile-case BWS (2 studies). Although limited and inconsistent, the balance of evidence suggests that preferences derived from DCE and profile-case BWS may not be concordant, regardless of the decision context. Preferences estimated from DCE and multiprofile-case BWS may be concordant (single study). Profile- and multiprofile-case BWS appear more statistically efficient than DCE, but no evidence is available to suggest they have a greater response efficiency. Little evidence suggests superior validity for one format over another. Participant acceptability may favour DCE, which had a lower self-reported task difficulty and was preferred over profile-case BWS in a priority setting but not necessarily in other decision contexts. DCE and profile-case BWS may be of equal validity but give different preference estimates regardless of the health context; thus, they may be measuring different constructs. Therefore, choice between methods is likely to be based on normative considerations related to coherence with theoretical frameworks and on pragmatic considerations related to ease of data collection.

Temporal dominance of sensations and preferences of Brazilians and Slovakians: A cross-cultural study of cachaças stored with woods from the Amazon rainforest.

PubMed

Simioni, Síntia Carla Corrêa; Tovar, Diego Mercado; Rodrigues, Jéssica Ferreira; de Souza, Vanessa Rios; Nunes, Cleiton Antônio; Vietoris, Vladimir; Pinheiro, Ana Carla Marques

2018-02-01

Brazilians and Slovakians evaluated the temporal profile and the acceptability of cachaça stored with different woods (Cumarurana (CM), Jatobá (JT) and, Louro-vermelho (LV), which are found in the Amazon rainforest, and also oak), with the aim of performing a cross-cultural comparison of the dynamic profile of the attributes perceived in the cachaças and the sensorial acceptance of the samples. Important differences were observed between the temporal sensorial profiles generated by the two groups and their preferences. Brazilians preferred cachaças stored with the traditional wood, oak, followed by those stored with JT and CM. In contrast, Slovakians preferred cachaças stored with JT, followed by those stored with LV and oak. For both countries, the dominance of wood flavor and vanilla attributes at the end of the analysis time was positively associated with acceptance, while the dominance of off-flavors and the wood flavor attribute at the beginning of the analysis time was negatively associated with acceptance for Brazilians and Slovakians, respectively. Brazilians preferred cachaça stored with oak wood, and Slovakians preferred cachaça stored with JT wood, with acceptability being strongly associated with the dominance of wood flavor and vanilla attributes at the end of the evaluation time. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Post-marketing safety surveillance conducted in Korea (2008-2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™).

PubMed

Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

2016-10-02

According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice.

A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance

PubMed Central

Akaza, Hideyuki; Oya, Mototsugu; Iijima, Masafumi; Hyodo, Ichinosuke; Gemma, Akihiko; Itoh, Hiroshi; Adachi, Masatoshi; Okayama, Yutaka; Sunaya, Toshiyuki; Inuyama, Lyo

2015-01-01

Objective Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. Methods All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Results Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand–foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7–8.1), and the overall survival rate at 1 year was 75.4% (73.5–77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. Conclusions Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials. PMID:26206897

A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.

PubMed

Harris, Jeffrey M; Maciuca, Romeo; Bradley, Mary S; Cabanski, Christopher R; Scheerens, Heleen; Lim, Jeremy; Cai, Fang; Kishnani, Mona; Liao, X Charlene; Samineni, Divya; Zhu, Rui; Cochran, Colette; Soong, Weily; Diaz, Joseph D; Perin, Patrick; Tsukayama, Miguel; Dimov, Dimo; Agache, Ioana; Kelsen, Steven G

2016-03-18

Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. ClinicalTrials.gov NCT01582503.

Prospective observational study of treatment pattern, effectiveness and safety of zoledronic acid therapy beyond 24 months in patients with multiple myeloma or bone metastases from solid tumors.

PubMed

Van den Wyngaert, T; Delforge, M; Doyen, C; Duck, L; Wouters, K; Delabaye, I; Wouters, C; Wildiers, H

2013-12-01

To study the treatment patterns, effectiveness and safety of zoledronic acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term treatment in daily clinical practice. Patients with multiple myeloma (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w ZOL therapy were followed prospectively for an additional 18 months beyond the 24 months required for study entry. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety. In all, 298 evaluable patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001) and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002) in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during the study as compared to before inclusion (0.12 vs. 0.13 events per person-year; p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67; p=0.002). Beyond 2 years of therapy, treatment patterns of ZOL were heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable, and interrupting ZOL in patients with solid tumors was associated with a higher risk of SREs.

A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance.

PubMed

Akaza, Hideyuki; Oya, Mototsugu; Iijima, Masafumi; Hyodo, Ichinosuke; Gemma, Akihiko; Itoh, Hiroshi; Adachi, Masatoshi; Okayama, Yutaka; Sunaya, Toshiyuki; Inuyama, Lyo

2015-10-01

Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand-foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5-77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials. © The Author 2015. Published by Oxford University Press.

Long-Term Safety and Effectiveness of the 'OptEase' Vena Cava Filter

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

Kalva, Sanjeeva P., E-mail: skalva@partners.org; Marentis, Theodore C.; Yeddula, Kalpana

Purpose: To assess the long-term safety and effectiveness of the OptEase inferior vena cava (IVC) filter. Materials and Methods: In this Institutional Review Board-approved, retrospective study, we reviewed data of 71 patients who received an OptEase filter at our institution from 2002 to 2007. Thirty-nine (55%) patients had symptoms of venous thromboembolism before filter placement. The indications for filter included contraindication to anticoagulation in 31 (44%) patients, prophylaxis against pulmonary embolism (PE) in 29 (41%) patients, and failure of anticoagulation in 11 (15%) patients. Procedure-related complications, such as symptomatic post-filter PE, deep venous thrombosis (DVT), IVC occlusion, and incidental imaging-evidentmore » filter-related complications, were recorded. Safety was assessed by the occurrence of filter-related complications during placement and follow-up. Effectiveness was assessed by the occurrence of post-filter PE. Results: Sixty-five (92%) filters were placed under fluoroscopy, and 6 (8%) were placed using intravascular ultrasound guidance. Seventy (99%) filters were placed successfully. Seven (10%) filters were placed in the suprarenal cava. Retrieval was attempted in 14 (20%) patients, and 12 filters were successfully retrieved. Clinical follow-up was available for 20 {+-} 21 months. Symptoms of postfilter PE and DVT occurred in 15% (n = 11) and 10% (n = 7) patients, respectively. None of these patients had computed tomography (CT)-proven PE, and only one had ultrasound-proven new DVT. One patient had symptomatic IVC occlusion. Follow-up abdominal CT in 20 patients showed thrombus in the filter in two of them. There were no instances of filter migration, filter tilt, or caval wall penetration. Conclusion: The OptEase filter appears to have an acceptable long-term safety profile. The filter was effective against PE.« less

Post-marketing safety surveillance conducted in Korea (2008–2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™)

PubMed Central

Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

2016-01-01

ABSTRACT Purpose: According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). Methods: During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. Results: A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. Conclusions: We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice. PMID:27494163

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

PubMed

Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo

2016-12-01

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.

PubMed

Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela

2016-09-01

Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Engineering in an age of anxiety

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

Weinberg, A.M.

Public fears of nuclear or chemical accidents should challenge engineers to build systems that are inherently safe. Much of our national anxiety focuses on modern technology. This anxiety places constraints on our technologies. Probabilistic risk assessment (PBA) has become an accepted tool for determining the safety of a device. Although PBA is widely accepted by engineers, it will not allay the public's anxieties. To concede that a technology has the potential for causing a major disaster, even if the probability of occurrence is minute, is unacceptable in the age of anxiety. The search for inherent safety concepts, that - informedmore » skeptics - and the public will accept, continues. The greenhouse effect may be decisive in spurring the demand for inherently safe nuclear technology. Ultimately what the public requires by way of assurance may well depend on the alternatives available. 11 refs.« less

Nuclear energy acceptance and potential role to meet future energy demand. Which technical/scientific achievements are needed?

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

Schenkel, Roland

25 years after Chernobyl, the Fukushima disaster has changed the perspectives of nuclear power. The disaster has shed a negative light on the independence, reliability and rigor of the national nuclear regulator and plant operator and the usefulness of the international IAEA guidelines on nuclear safety. It has become clear that, in the light of the most severe earthquake in the history of Japan, the plants at Fukushima Daiichi were not adequately protected against tsunamis. Nuclear acceptance has suffered enormously and has changed the perspectives of nuclear energy dramatically in countries that have a very risk-sensitive population, Germany is anmore » example. The paper analyses the reactions in major countries and the expected impact on future deployment of reactors and on R and D activities. On the positive side, the disaster has demonstrated a remarkable robustness of most of the 14 reactors closest to the epicentre of the Tohoku Seaquake although not designed to an event of level 9.0. Public acceptance can only be regained with a rigorous and worldwide approach towards inherent reactor safety and design objectives that limit the impact of severe accidents to the plant itself (like many of the new Gen III reactors). A widespread release of radioactivity and the evacuation (temporary or permanent) of the population up to 30 km around a facility are simply not acceptable. Several countries have announced to request more stringent international standards for reactor safety. The IAEA should take this move forward and intensify and strengthen the different peer review mission schemes. The safety guidelines and peer reviews should in fact become legally binding for IAEA members. The paper gives examples of the new safety features developed over the last 20 years and which yield much safer reactors with lesser burden to the environment under severe accident conditions. The compatibility of these safety systems with the current concepts for fusion-fission hybrids, which have recently been proposed for energy production, is critically reviewed. There are major challenges remaining that are shortly outlined. Scientific/technical achievements that are required in the light of the Fukushima accident are highlighted.« less

Nuclear energy acceptance and potential role to meet future energy demand. Which technical/scientific achievements are needed?

NASA Astrophysics Data System (ADS)

Schenkel, Roland

2012-06-01

25 years after Chernobyl, the Fukushima disaster has changed the perspectives of nuclear power. The disaster has shed a negative light on the independence, reliability and rigor of the national nuclear regulator and plant operator and the usefulness of the international IAEA guidelines on nuclear safety. It has become clear that, in the light of the most severe earthquake in the history of Japan, the plants at Fukushima Daiichi were not adequately protected against tsunamis. Nuclear acceptance has suffered enormously and has changed the perspectives of nuclear energy dramatically in countries that have a very risk-sensitive population, Germany is an example. The paper analyses the reactions in major countries and the expected impact on future deployment of reactors and on R&D activities. On the positive side, the disaster has demonstrated a remarkable robustness of most of the 14 reactors closest to the epicentre of the Tohoku Seaquake although not designed to an event of level 9.0. Public acceptance can only be regained with a rigorous and worldwide approach towards inherent reactor safety and design objectives that limit the impact of severe accidents to the plant itself (like many of the new Gen III reactors). A widespread release of radioactivity and the evacuation (temporary or permanent) of the population up to 30 km around a facility are simply not acceptable. Several countries have announced to request more stringent international standards for reactor safety. The IAEA should take this move forward and intensify and strengthen the different peer review mission schemes. The safety guidelines and peer reviews should in fact become legally binding for IAEA members. The paper gives examples of the new safety features developed over the last 20 years and which yield much safer reactors with lesser burden to the environment under severe accident conditions. The compatibility of these safety systems with the current concepts for fusion-fission hybrids, which have recently been proposed for energy production, is critically reviewed. There are major challenges remaining that are shortly outlined. Scientific/technical achievements that are required in the light of the Fukushima accident are highlighted.

An Assessment of Software Safety as Applied to the Department of Defense Software Development Process

DTIC Science & Technology

1992-12-01

provide program 5 managers some level of confidence that their software will operate at an acceptable level of risk. A number of structured safety...safety within the constraints of operational effectiveness, schedule, and cost through timely application of system safety management and engineering...Master of Science in Software Systems Management Peter W. Colan, B.S.E. Robert W. Prouhet, B.S. Captain, USAF Captain, USAF December 1992 Approved for

Light duty utility arm phase 2 qualification test procedure

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

Barnes, G.A.

1997-01-16

This Acceptance Test Procedure (ATP) will test and verify that the Exhauster meets the specified functional requirements, safety requirements, operating requirements, and provide a record of the functional test results. The system/functions that will be tested are listed in the scope section of the Acceptance Test Procedure.

49 CFR 195.228 - Welds and welding inspection: Standards of acceptability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Welds and welding inspection: Standards of... SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE Construction § 195.228 Welds and welding inspection: Standards of acceptability. (a) Each weld and welding must be inspected to insure compliance with...

30 CFR 18.16 - Withdrawal of approval, certification, or acceptance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Withdrawal of approval, certification, or acceptance. 18.16 Section 18.16 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES...

49 CFR 195.228 - Welds and welding inspection: Standards of acceptability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Welds and welding inspection: Standards of... SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE Construction § 195.228 Welds and welding inspection: Standards of acceptability. (a) Each weld and welding must be inspected to insure compliance with...

49 CFR 195.228 - Welds and welding inspection: Standards of acceptability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Welds and welding inspection: Standards of... SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE Construction § 195.228 Welds and welding inspection: Standards of acceptability. (a) Each weld and welding must be inspected to insure compliance with...

49 CFR 195.228 - Welds and welding inspection: Standards of acceptability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Welds and welding inspection: Standards of... SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE Construction § 195.228 Welds and welding inspection: Standards of acceptability. (a) Each weld and welding must be inspected to insure compliance with...

49 CFR 195.228 - Welds and welding inspection: Standards of acceptability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Welds and welding inspection: Standards of... SAFETY TRANSPORTATION OF HAZARDOUS LIQUIDS BY PIPELINE Construction § 195.228 Welds and welding inspection: Standards of acceptability. (a) Each weld and welding must be inspected to insure compliance with...

Sex differences in principal farm operators' tractor driving safety beliefs and behaviors.

PubMed

Cole, H P; Westneat, S C; Browning, S R; Piercy, L R; Struttmann, T

2000-01-01

To examine the widely accepted hypothesis that farm women are more concerned with safety issues and behaviors than their male counterparts are. A telephone survey was administered to a random sample of Kentucky principal farm operators, 90 of whom were women. Participants were questioned about their tractor safety beliefs and practices. No significant sex differences in tractor safety perceptions and behavior were observed. Socialization of women to the role of principal farm operator may override their typically greater sensitivity to safety issues, an important consideration when designing safety campaigns for this population.

Child Safety Programs: Implications Affecting Use of Child Restraints.

ERIC Educational Resources Information Center

Hoadley, Michael R.; And Others

1981-01-01

A study identified behavioral and attitudinal factors influencing the use of child restraints in automobiles. The data suggest that the focus of safety education needs to be aimed at both child and parent acceptance and understanding of the importance of restraint use. (JN)

Lesinurad for the treatment of hyperuricaemia in people with gout.

PubMed

Robinson, Philip C; Dalbeth, Nicola

2017-12-01

Gout is a common form of inflammatory arthritis caused by deposition of monosodium urate crystals. The central strategy for effective long-term management of gout is serum urate lowering. Current urate-lowering drugs include both xanthine oxidase inhibitors and uricosuric agents. Lesinurad is a URAT1 inhibitor that selectively inhibits urate rebsorption at the proximal renal tubule. Lesinurad 200mg daily in combination with a xanthine oxidase is approved for urate-lowering therapy in patients with gout. Areas covered: The published literature was searched using Pubmed and additional information was obtained from publically available regulatory documents. Pre-clinical data and clinical trials of lesinurad are described. Serum urate-lowering efficacy and effects on other clinical endpoints are discussed. Adverse event data, focusing on renal safety are also presented. Expert opinion: Lesinurad is an effective urate-lowering drug that has a generally acceptable safety profile when used at 200mg daily dosing in combination with a xanthine oxidase inhibitor. The recent approval of fixed dose combination pills of lesinurad with allopurinol is an important step in improving adherence and reducing risk of renal adverse events. It remains to be seen if this therapy will provide additional benefit for gout management above improved use of widely available generic therapies.

271 Evaluation of Adverse Events Associated to Administration of Omalizumab

PubMed Central

Gomez, R. Maximiliano; Vinuesa, Miguel; Teijeiro, Alvaro; Ivancevich, Juan Carlos; Jares, Edgardo; Baena-Cagnani, Carlos E.

2012-01-01

Background Anti IgE therapy is the ultimate therapeutic option for severe atopic conditions, not controlled by conventional treatment. Its efficacy and safety was described in several peer reviewed publications. Here we report on the events temporally related to the administration of almost 4 hundred doses of the only monoclonal Anti IgE antibody approved in our country for the treatment of severe asthma. Methods Descriptive retrospective analysis of clinical charts of patients receiving omalizumab because of Severe Uncontrolled Asthma, considering those events presented in the 72 hours after administration of it, which was not present before the procedure or as a concomitant condition of the patient. Vital signs, respiratory and cardiovascular evaluation, and dermatological inspection were performed in the hour after administration of corresponding doses. Patients having any kind of complaint were evaluated in unscheduled visits. Results 384 doses of 150 mg omalizumab were given to from April 2007 to June 2011, to nine severe asthmatic patients. One of them received treatment for over 4 years, and two for over 3 years. Conclusions Our records from patients receiving omalizumab have not registered severe adverse events in almost four hundred doses given. The moderate adverse events of nausea and tachycardia resulted in discontinuation of treatment in this unique patient. Overall, omalizumab demonstrated a very acceptable safety profile in our patients.

Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis.

PubMed

Mou, Shan; Li, Jialin; Yu, Zanzhe; Wang, Qin; Ni, Zhaohui

2013-02-01

An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.

Laminar-airflow equipment certification: what the pharmacist needs to know.

PubMed

Bryan, D; Marback, R C

1984-07-01

The basic information pharmacy practitioners need to determine the suitability and applicability of laminar-airflow equipment test standards and procedures is presented. The operative guideline for any laminar-flow clean bench (LFCB) certification is the cleanroom and work station requirements for controlled environments as defined by the federal government under Federal Standard 209b (FS 209b). FS 209b outlines the tests, test procedures, and acceptable performance ranges for all LFCB equipment. National Sanitation Foundation Standard Number 49 (NSF 49) is used in the certification of biological-safety cabinets (BSCs). NSF 49 covers those aspects of safety, maintenance, performance, and testing that are unique BSCs. To monitor certification properly, practitioners should be familiar with these standards and the air-velocity profile, high-efficiency particulate air filter performance, noise output, light, and electrical test procedures. A review of the requisite knowledge, experience, and reputation of certifying agents is presented, along with an outline of all the necessary procedures, equipment, and documentation to be used in the process. A thorough test report should be issued upon unit certification. As pharmacy practitioners are responsible for all other aspects of quality assurance, they should also be capable of auditing these certifications to ensure the aseptic quality of products compounded in the laminar-airflow environment.

Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol (Alesse). North american Levonorgestrel Study Group (NALSG).

PubMed

Archer, D F; Maheux, R; DelConte, A; O'Brien, F B

1999-11-01

The efficacy and safety of a low-dose 21-day combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol were evaluated in an open-label, multicenter trial. A total of 1708 subjects with regular menstrual cycles (27,011 cycles) were evaluated. The oral contraceptive was administered once a day for 21 days, followed by 7 days of placebo for a complete cycle. During 26,554 cycles evaluated for efficacy, 18 pregnancies occurred (Pearl index of 0.88); 6 of these events were attributable to subject noncompliance. After 30 cycles of exposure the cumulative rate of withdrawal as a result of accidental pregnancy was 1.9%. Breakthrough bleeding (with or without spotting) occurred in 12.9% of the cycles and spotting alone occurred in 10.1% of the cycles. The 2 most common adverse events cited as reasons for discontinuation were headache (2% of subjects) and metrorrhagia (2%). One serious event led to withdrawal of a subject. Overall, the results of this study demonstrate that the monophasic regimen of 100 microg levonorgestrel and 20 microg ethinyl estradiol offers effective contraception, acceptable cycle control, and a good tolerability profile.

A 12-week intramuscular toxicity study of risperidone-loaded microspheres in Beagle dogs.

PubMed

Tian, J; Wang, W; Ye, L; Cen, X; Guan, X; Zhang, J; Yu, P; Du, G; Liu, W; Li, Y

2014-05-01

Long-acting formulations of antipsychotics are important treatment options to increase the compliance of schizophrenic patients. Risperidone, a 5-HT2 and dopaminergic D2 receptor antagonist, was developed as long-acting sustained-release microspheres with poly(lactide-co-glycolide) (PLGA) as a drug carrier for the treatment of schizophrenia. In the present study, the main objective is to determine the nonclinical safety profile of risperidone-loaded microspheres (RM) in Beagle dogs after intramuscular administration for 3 months, once in 2 weeks, followed by 8-week recovery phase. No animal death was found and no special toxicological findings were observed. The findings, such as hypoactivity, ptosis, increased heart rate, and elevated serum and pituitary prolactin levels, were observed and related to the pharmacological effects of risperidone. The changes in the reproductive system (uterus, ovary, vagina, cervix, and mammary gland) were considered secondary to the prolactin elevation, and the congestion of spleen was related to risperidone. The foreign body granulomas at injection sites might be caused by PLGA. At the end of recovery phase, the above changes mostly recovered to normal, and on administering 3 mg/kg dose level once in 2 weeks on Beagle dogs showed no observed adverse effect. Taken together, RM had exhibited the acceptable safety.

Nonrenal toxicities of acetaminophen, aspirin, and nonsteroidal anti-inflammatory agents.

PubMed

Matzke, G R

1996-07-01

Approximately 2% of the United States population consumes an analgesic, antipyretic, or nonsteroidal antiinflammatory drug (NSAID) each day. Aspirin and acetaminophen have been available to the public without a prescription (over-the-counter) for decades, while most NSAIDs are still only available with a prescription from a physician. The recent trend of switching NSAIDs from prescription to over-the-counter status may be perceived by some as an indication of their inherent safety. However, all these agents have been associated with a unique but overlapping safety profile. In fact, significant adverse events (AEs) on multiple organ systems, including the kidney and gastrointestinal tract, have been reported with most of these agents. In this review, the incidence of the nonrenal AEs of aspirin, acetaminophen, and selected NSAIDs are tabulated. The strengths of the causative associations are highlighted, the relative risks for the gastrointestinal and cardiovascular AEs are discussed, and the relationship to patient risk factors and drug characteristics, such as dose and half-life, are reviewed. The selection of the optimal agent for an individual patient depends on the balance between the desired pharmacodynamic response, the patient's pharmacotherapy history, and the degree of AE risk one is willing to accept. Therapy should be initiated in all settings with the lowest possible dosage since the incidence of the major AEs is dose related.

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.

Probabilistic Requirements (Partial) Verification Methods Best Practices Improvement. Variables Acceptance Sampling Calculators: Empirical Testing. Volume 2

NASA Technical Reports Server (NTRS)

Johnson, Kenneth L.; White, K. Preston, Jr.

2012-01-01

The NASA Engineering and Safety Center was requested to improve on the Best Practices document produced for the NESC assessment, Verification of Probabilistic Requirements for the Constellation Program, by giving a recommended procedure for using acceptance sampling by variables techniques as an alternative to the potentially resource-intensive acceptance sampling by attributes method given in the document. In this paper, the results of empirical tests intended to assess the accuracy of acceptance sampling plan calculators implemented for six variable distributions are presented.

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.

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

[Comics for traffic education: evaluation of a traffic safety campaign].

PubMed

Bonfadelli, H

1989-01-01

Traffic safety campaigns often are ineffective to change driving behavior because they don't reach the target group or are recognized only by people who are already interested or concerned. The evaluation of a traffic safety campaign called "Leo Lässig", addressed to young new drivers, shows that recognition and acceptance by the target group were stimulated by the age-conform means of comic-strips.

Using Modified-ISS Model to Evaluate Medication Administration Safety During Bar Code Medication Administration Implementation in Taiwan Regional Teaching Hospital.

PubMed

Ma, Pei-Luen; Jheng, Yan-Wun; Jheng, Bi-Wei; Hou, I-Ching

2017-01-01

Bar code medication administration (BCMA) could reduce medical errors and promote patient safety. This research uses modified information systems success model (M-ISS model) to evaluate nurses' acceptance to BCMA. The result showed moderate correlation between medication administration safety (MAS) to system quality, information quality, service quality, user satisfaction, and limited satisfaction.

Companies' opinions and acceptance of global food safety initiative benchmarks after implementation.

PubMed

Crandall, Phil; Van Loo, Ellen J; O'Bryan, Corliss A; Mauromoustakos, Andy; Yiannas, Frank; Dyenson, Natalie; Berdnik, Irina

2012-09-01

International attention has been focused on minimizing costs that may unnecessarily raise food prices. One important aspect to consider is the redundant and overlapping costs of food safety audits. The Global Food Safety Initiative (GFSI) has devised benchmarked schemes based on existing international food safety standards for use as a unifying standard accepted by many retailers. The present study was conducted to evaluate the impact of the decision made by Walmart Stores (Bentonville, AR) to require their suppliers to become GFSI compliant. An online survey of 174 retail suppliers was conducted to assess food suppliers' opinions of this requirement and the benefits suppliers realized when they transitioned from their previous food safety systems. The most common reason for becoming GFSI compliant was to meet customers' requirements; thus, supplier implementation of the GFSI standards was not entirely voluntary. Other reasons given for compliance were enhancing food safety and remaining competitive. About 54 % of food processing plants using GFSI benchmarked schemes followed the guidelines of Safe Quality Food 2000 and 37 % followed those of the British Retail Consortium. At the supplier level, 58 % followed Safe Quality Food 2000 and 31 % followed the British Retail Consortium. Respondents reported that the certification process took about 10 months. The most common reason for selecting a certain GFSI benchmarked scheme was because it was widely accepted by customers (retailers). Four other common reasons were (i) the standard has a good reputation in the industry, (ii) the standard was recommended by others, (iii) the standard is most often used in the industry, and (iv) the standard was required by one of their customers. Most suppliers agreed that increased safety of their products was required to comply with GFSI benchmarked schemes. They also agreed that the GFSI required a more carefully documented food safety management system, which often required improved company food safety practices and increased employee training. Adoption of a GFSI benchmarked scheme resulted in fewer audits, i.e., one less per year. An educational opportunity exists to acquaint retailers and suppliers worldwide with the benefits of having an internationally recognized certification program such as that recognized by the GFSI.

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

Evaluation of Nurses' Acceptance of Screen Display Methods with Temporarily Non-Display for Privacy Protection.

PubMed

Niimi, Yukari; Ota, Katsumasa; Ikegami, Chikako

2018-01-01

The purpose of this study was to explore nurses' acceptance of a screen display method that temporarily hides patient information for privacy protection. Using a questionnaire, we asked nurses to evaluate the display method from the viewpoints of safety and efficiency with respect to 22 personal information items. The nurses were favorably interested in introducing the display method into their hospital system; however, their acceptance varied.

Statewide implementation of the total pavement acceptance device (TPAD) : final report.

DOT National Transportation Integrated Search

2016-07-01

Construction and development of the Total Pavement Acceptance Device (TPAD) was completed at the end of August 2012 through TxDOT Research Project 0-6005-01. The TPAD is a multi-function pavement evaluation device used to profile continuously along p...

The acceptability and safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and soil-transmitted helminthiasis in children aged 1-4 years in Uganda.

PubMed

Namwanje, Harriet; Kabatereine, Narcis B; Olsen, Annette

2011-10-01

There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Evaluating the Effects of Gamma-Irradiation for Decontamination of Medicinal Cannabis.

PubMed

Hazekamp, Arno

2016-01-01

In several countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment by gamma irradiation currently seems the only method available to meet these requirements. We evaluated the effects of irradiation treatment of four different cannabis varieties covering different chemical compositions. Samples were compared before and after standard gamma-irradiation treatment by performing quantitative UPLC analysis of major cannabinoids, as well as qualitative GC analysis of full cannabinoid and terpene profiles. In addition, water content and microscopic appearance of the cannabis flowers was evaluated. This study found that treatment did not cause changes in the content of THC and CBD, generally considered as the most important therapeutically active components of medicinal cannabis. Likewise, the water content and the microscopic structure of the dried cannabis flowers were not altered by standard irradiation protocol in the cannabis varieties studied. The effect of gamma-irradiation was limited to a reduction of some terpenes present in the cannabis, but keeping the terpene profile qualitatively the same. Based on the results presented in this report, gamma irradiation of herbal cannabis remains the recommended method of decontamination, at least until other more generally accepted methods have been developed and validated.

Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid.

PubMed

Kumar, Abhinav; Bicer, Elif Melis; Morgan, Anna Babin; Pfeffer, Paul E; Monopoli, Marco; Dawson, Kenneth A; Eriksson, Jonny; Edwards, Katarina; Lynham, Steven; Arno, Matthew; Behndig, Annelie F; Blomberg, Anders; Somers, Graham; Hassall, Dave; Dailey, Lea Ann; Forbes, Ben; Mudway, Ian S

2016-05-01

When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles. Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics. Copyright © 2016. Published by Elsevier Inc.

Evaluating the Effects of Gamma-Irradiation for Decontamination of Medicinal Cannabis

PubMed Central

Hazekamp, Arno

2016-01-01

In several countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment by gamma irradiation currently seems the only method available to meet these requirements. We evaluated the effects of irradiation treatment of four different cannabis varieties covering different chemical compositions. Samples were compared before and after standard gamma-irradiation treatment by performing quantitative UPLC analysis of major cannabinoids, as well as qualitative GC analysis of full cannabinoid and terpene profiles. In addition, water content and microscopic appearance of the cannabis flowers was evaluated. This study found that treatment did not cause changes in the content of THC and CBD, generally considered as the most important therapeutically active components of medicinal cannabis. Likewise, the water content and the microscopic structure of the dried cannabis flowers were not altered by standard irradiation protocol in the cannabis varieties studied. The effect of gamma-irradiation was limited to a reduction of some terpenes present in the cannabis, but keeping the terpene profile qualitatively the same. Based on the results presented in this report, gamma irradiation of herbal cannabis remains the recommended method of decontamination, at least until other more generally accepted methods have been developed and validated. PMID:27199751

The effect of safety factor profile on transport in steady-state, high-performance scenarios

DOE PAGES

Holcomb, C. T.; Ferron, J. R.; Luce, T. C.; ...

2012-03-09

In this study, an analysis of the dependence of transport on the safety factor profile in high-performance, steady-state scenario discharges is presented. This is based on experimental scans of q 95 and q min taken with fixed β N, toroidal field, double-null plasma shape, divertor pumping, and electron cyclotron current drive input. The temperature and thermal diffusivity profiles were found to vary considerably with the q-profile, and these variations were significantly different for electrons and ions. With fixed q 95, both temperature profiles increase and broaden as q min is increased and the magnetic shear becomes low or negative inmore » the inner half radius, but these temperature profile changes are stronger for the electrons. Power balance calculations show the peak in the ion thermal diffusivity (χ i) at ρ – 0.6 – 0.8 increases with q 95 or q min.« less

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.

Wind velocity profile reconstruction from intensity fluctuations of a plane wave propagating in a turbulent atmosphere.

PubMed

Banakh, V A; Marakasov, D A

2007-08-01

Reconstruction of a wind profile based on the statistics of plane-wave intensity fluctuations in a turbulent atmosphere is considered. The algorithm for wind profile retrieval from the spatiotemporal spectrum of plane-wave weak intensity fluctuations is described, and the results of end-to-end computer experiments on wind profiling based on the developed algorithm are presented. It is shown that the reconstructing algorithm allows retrieval of a wind profile from turbulent plane-wave intensity fluctuations with acceptable accuracy.

[Weighing use and safety of therapeutic agents and feed additives (author's transl)].

PubMed

van der Wal, P

1982-02-01

(1) The pros and cons of using feed additives and therapeutic agents may be successfully weighed in the light of carefully considered consumer requirements. (2) The socio-economic interests of the producer and the welfare of the animal will also determine the response of the production apparatus to consumer requirements. (3) Consumption of the current amounts of products of animal origin and maintenance of price and quality will only be feasible in the event of rational large-scale production in which constituents used in nutrition, prophylaxis and therapeutics are highly important factors. (4) Using these ingredients should be preceded by accurate evaluation of their use and safety. Testing facilities, conduct of studies and reporting should be such as to make the results nationally and internationally acceptable to all those concerned. (5) In deciding whether feed constituents are acceptable in view of the established use and safety, compliance will have to be sought with those standards which are accepted in other fields of society. Measures which result in raising the price of food without actually helping to reduce the risks to the safety of man, animals and environment, are likely to be rejected by any well-informed consumer who is aware of the facts. (6) For accurate weighing of use and safety at a national level, possibilities are hardly adequate in Europe. Decisions reached within the framework of the European Community, also tuned to U.S.A.- conditions are rightly encouraged. A centrally managed professionally staffed and equipped test system in the European Community would appear to be indispensable.

76 FR 7853 - Patient Safety Organizations: Voluntary Delisting From Apollo Publishing, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... Organizations: Voluntary Delisting From Apollo Publishing, Inc. AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Notice of Delisting. SUMMARY: Apollo Publishing, Inc.: AHRQ has accepted a notification of voluntary relinquishment from Apollo Publishing, Inc., of its status as a Patient Safety...

VPP Star recognition

NASA Image and Video Library

2011-06-09

Stennis Space Center Deputy Director Rick Gilbrech (right) accepts a plaque designating the test facility as a Voluntary Protection Program Star site. Presenting the plaque is Clyde Payne, area director for the Occupational Safety and Health Administration in Jackson, Miss. OSHA established VPP in 1982 as a proactive safety management model to recognize excellence in safety and health. Since then, more than 2,000 organizations have been designated VPP Star sites. To reach that goal, an organization must demonstrate comprehensive and successful safety and health management programs in the workplace.

Safety analysis report for the Waste Storage Facility. Revision 2

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

Bengston, S.J.

1994-05-01

This safety analysis report outlines the safety concerns associated with the Waste Storage Facility located in the Radioactive Waste Management Complex at the Idaho National Engineering Laboratory. The three main objectives of the report are: define and document a safety basis for the Waste Storage Facility activities; demonstrate how the activities will be carried out to adequately protect the workers, public, and environment; and provide a basis for review and acceptance of the identified risk that the managers, operators, and owners will assume.

Peer Acceptance of Children with Language and Communication Impairments in a Mainstream Primary School: Associations with Type of Language Difficulty, Problem Behaviours and a Change in Placement Organization

ERIC Educational Resources Information Center

Laws, Glynis; Bates, Geraldine; Feuerstein, Maike; Mason-Apps, Emily; White, Catherine

2012-01-01

This research investigated peer acceptance of children with language and communication impairments attending a language resource base attached to a mainstream school. Compared to other children in their mainstream peer groups, peer acceptance was poor. Peer rejection was more common for children with profiles consistent with an autistic spectrum…

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

Influenza vaccines: Evaluation of the safety profile

PubMed Central

Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

2018-01-01

ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial

PubMed Central

Gulley, James L.; Rajan, Arun; Spigel, David R.; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J. L.; Leach, Joseph; Edenfield, W. Jeff; Wang, Ding; Grote, Hans Juergen; von Heydebreck, Anja; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

2017-01-01

Background Avelumab, a fully human IgG1 immune checkpoint inhibitor targeting programmed death ligand 1 (PD-L1), has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours. Here, we assessed avelumab treatment in patients with advanced, platinum-treated non-small cell lung cancer (NSCLC). Methods In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 sites in the United States. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or nonsquamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary endpoint was safety and tolerability. Secondary endpoints included best overall response, progression-free survival, overall survival, and clinical activity associated with PD-L1 expression. Responses were evaluated using RECIST v1.1, and analyses of antitumour activity and safety were performed in all patients who received at least one dose of avelumab. This trial is registered with ClinicalTrials.gov (NCT01772004); enrolment in this cohort is closed and the trial is ongoing. Findings Between 10 September 2013 and 24 June 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (interquartile range [first and third quartiles], 7·2–11·9 months). The most common treatment-related adverse events of any grade were fatigue (n=46; 25%), infusion-related reaction (n=38; 21%), and nausea (n=23; 13%). Grade ≥3 treatment-related adverse events occurred in 23 of 184 patients (13%); the most common were infusion-related reaction (n=4; 2%), elevated lipase (n=3; 2%), constipation (n=2; 1%), and dyspnoea (n=2; 1%). 16 of 184 patients (9%) had a serious adverse event related to treatment with avelumab, with infusion-related reaction (4 [2%]) and dyspnoea (2 [1%]) occurring in more than one patient. Immune-related treatment-related events occurred in 22 patients (12%). The confirmed objective response rate, regardless of PD-L1 status, was 12% (95% CI, 8–18), including one complete response and 21 partial responses. Seventy patients had stable disease, for an overall disease-control rate of 50%. Interpretation Avelumab showed an acceptable safety profile and antitumour activity in patients with progressive or resistant NSCLC, providing a rationale for additional studies of avelumab in this disease setting. Funding Merck KGaA, Darmstadt, Germany and Pfizer, Inc, New York, USA. PMID:28373005

World Trade Organization, ILO conventions, and workers' compensation.

PubMed

LaDou, Joseph

2005-01-01

The World Trade Organization, the World Bank, and the International Monetary Fund can assist in the implementation of ILO Conventions relating to occupational safety and health in developing countries. Most countries that seek to trade globally receive permission to do so from the WTO. If the WTO required member countries to accept the core ILO Conventions relating to occupational safety and health and workers' compensation, it could accomplish something that has eluded international organizations for decades. International workers' compensation standards are seldom discussed, but may at this time be feasible. Acceptance of a minimum workers' compensation insurance system could be a requirement imposed on applicant nations by WTO member states.

Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability

PubMed Central

Abrouk, Michael; Levin, Ethan; Brodsky, Merrick; Gandy, Jessica R; Nakamura, Mio; Zhu, Tian Hao; Farahnik, Benjamin; Koo, John; Bhutani, Tina

2016-01-01

Introduction The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. PMID:29387603

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 ...

Effectiveness and driver acceptance of a semi-autonomous forward obstacle collision avoidance system.

PubMed

Itoh, Makoto; Horikome, Tatsuya; Inagaki, Toshiyuki

2013-09-01

This paper proposes a semi-autonomous collision avoidance system for the prevention of collisions between vehicles and pedestrians and objects on a road. The system is designed to be compatible with the human-centered automation principle, i.e., the decision to perform a maneuver to avoid a collision is made by the driver. However, the system is partly autonomous in that it turns the steering wheel independently when the driver only applies the brake, indicating his or her intent to avoid the obstacle. With a medium-fidelity driving simulator, we conducted an experiment to investigate the effectiveness of this system for improving safety in emergency situations, as well as its acceptance by drivers. The results indicate that the system effectively improves safety in emergency situations, and the semi-autonomous characteristic of the system was found to be acceptable to drivers. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

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

9 CFR 351.14 - Processes to be supervised; extent of examinations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... examinations. 351.14 Section 351.14 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT... be at least once a month if the plant consistently handles only raw materials acceptable under § 351... consistently handles some raw materials that are acceptable, and some that are unacceptable, under § 351.3, for...

75 FR 76405 - Winter Bee, Inc., Provisional Acceptance of a Settlement Agreement and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... CONSUMER PRODUCT SAFETY COMMISSION [CPSC Docket No. 11-C0002] Winter Bee, Inc., Provisional...(e).\\1\\ Published below is a provisionally-accepted Settlement Agreement with Winter Bee, Inc... 1. In accordance with 16 CFR 1118.20, Winter Bee, Inc. (``Winter Bee'') and the staff (``Staff'') of...

42 CFR 484.18 - Condition of participation: Acceptance of patients, plan of care, and medical supervision.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., and medical supervision. Patients are accepted for treatment on the basis of a reasonable expectation... a doctor of medicine, osteopathy, or podiatric medicine. (a) Standard: Plan of care. The plan of... treatments, any safety measures to protect against injury, instructions for timely discharge or referral, and...

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.

Sensory Profile, Drivers of Liking, and Influence of Information on the Acceptance of Low-Calorie Synbiotic and Probiotic Chocolate Ice Cream.

PubMed

Peres, Juliana; Esmerino, Erick; da Silva, Alessandra Lins; Racowski, Ilana; Bolini, Helena

2018-05-01

The objective of this study was to evaluate the sensory profile and the influence of the information on the acceptance of the symbiotic chocolate ice cream made with sucrose and different sweeteners (aspartame, sucralose, neotame, Stevia with 60%, 85%, 95%, and 97% of rebaudioside A) through analysis of variance (ANOVA), Tukey's test, and partial least of square (PLS) regression. Quantitative descriptive analysis (QDA) was carried out by 18 assessors, who evaluated the samples in relation to the raised descriptors. Additionally, two acceptance tests (blind/informed) were performed with 120 consumers. The samples sweetened with sucralose and rebaudioside 97% presented similar profile to the control sample, thus having a better potential to replace sucrose in chocolate ice cream. The acceptance test carried out with information had higher scores for the attributes appearance, aroma, flavor, texture, and overall impression. The correlation between data from the acceptance tests and QDA showed that the descriptors "low-energy" and "natural sweetener" claims interfered negatively in the drivers of liking of chocolate ice cream. Therefore, we can conclude that some characteristics unnoticed by consumers were highlighted after providing the information about the product's characteristics. This research is important and contributes to the manufacture and development of low-calorie chocolate ice cream with functional properties, guiding, through suitable sensory and statistical tools, the application of stevia and other artificial sweeteners in products with reduction or total absence of sucrose and highlighting the impact of the labeling of these products on consumer perception. © 2018 Institute of Food Technologists®.

Child Safety: It's No Accident. An Issue Statement.

ERIC Educational Resources Information Center

Virginia State Div. for Children, Richmond.

The three major causes of injury and mortality among children in the state of Virginia are, in order of frequency, automobile-related accidents, poison ingestion, and suicide. With respect to injuries sustained in automobile accidents, adults traveling with children by car must accept responsibility for the safety of child passengers. Acute…

Managing pedestrian safety II : A case-control study of collision locations on state routes in King County and Seattle, Washington

DOT National Transportation Integrated Search

2008-01-01

The safety of non-motorized transportation systems is essential to the public acceptance and overall success of Washington State's and local jurisdictions' efforts to reduce congestion. The State's and the jurisdictions' goals to increase non-SOV (si...

Evaluation of interactive highway safety design model crash prediction tools for two-lane rural roads on Kansas Department of Transportation projects.

DOT National Transportation Integrated Search

2014-01-01

Historically, project-level decisions for the selection of highway features to promote safety were : based on either engineering judgment or adherence to accepted national guidance. These tools have allowed : highway designers to produce facilities t...

Evaluation of interactive highway safety design model crash prediction tools for two-lane rural roads on Kansas Department of Transportation projects : [technical summary].

DOT National Transportation Integrated Search

2014-01-01

Historically, project-level decisions for the selection of highway features to promote safety were based on either engineering judgment or adherence to accepted national guidance. These tools have allowed highway designers to produce facilities that ...

49 CFR Appendix B to Part 385 - Explanation of Safety Rating Process

Code of Federal Regulations, 2011 CFR

2011-10-01

...-employment controlled substance test result (critical). § 382.303(a)Failing to conduct post accident testing... controls in place that function effectively to ensure acceptable compliance with the applicable safety... are those identified as such where noncompliance relates to management and/or operational controls...

49 CFR Appendix B to Part 385 - Explanation of Safety Rating Process

Code of Federal Regulations, 2010 CFR

2010-10-01

...-employment controlled substance test result (critical). § 382.303(a)Failing to conduct post accident testing... controls in place that function effectively to ensure acceptable compliance with the applicable safety... are those identified as such where noncompliance relates to management and/or operational controls...

30 CFR 6.10 - Use of independent laboratories.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PRODUCT SAFETY STANDARDS § 6.10 Use of independent laboratories. (a) MSHA will accept testing and... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Use of independent laboratories. 6.10 Section 6.10 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION...

42 CFR 37.42 - Approval of roentgenographic facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Roentgenology, Radium Therapy and Nuclear Medicine,” Vol. 117, No. 4, April 1973. (c) Each roentgenographic.... The form shall include: (1) The date of the last radiation safety inspection by an appropriate...; and (4) the date of acquisition of the X-ray unit. To be acceptable, the radiation safety inspection...

Designing with Traffic Safety in Mind.

ERIC Educational Resources Information Center

Matthews, John

1998-01-01

Provides an example of how one county public school system was able to minimize traffic accidents and increase safety around its schools. Illustrations are provided of safer bus loading zones, pedestrian walkways and sidewalks, staff parking, and acceptable methods for staging buses. A checklist for school driveway design concludes the article.…

Infusing Some Queer into Teacher Education

ERIC Educational Resources Information Center

Turnbull, Miles; Hilton, Tom

2010-01-01

Publically-funded schools in North America are often scary and dangerous places for gay, lesbian, bisexual, transgendered, and questioning (GBLTQ) youth, and many teens suggest that the adults charged with ensuring their safety and learning often do little to promote their acceptance and safety among their peers. Educators need preparation to…

Communicating for Safety's Sake

ERIC Educational Resources Information Center

Wiesner, Robert

2005-01-01

No community is safe until every member takes responsibility for the community's collective safety. College communities are no different from families, towns and businesses in that respect. Getting everyone to accept responsibility is a challenge and skilled communication is an important component of the solution. As part of the front line,…

Addressing Younger Workers' Needs: The Promoting U through Safety and Health (PUSH) Trial Outcomes.

PubMed

Rohlman, Diane S; Parish, Megan; Elliot, Diane L; Hanson, Ginger; Perrin, Nancy

2016-08-10

Most younger workers, less than 25 years old, receive no training in worker safety. We report the feasibility and outcomes of a randomized controlled trial of an electronically delivered safety and health curriculum for younger workers entitled, PUSH (Promoting U through Safety and Health). All younger workers (14-24 years old) hired for summer work at a large parks and recreation organization were invited to participate in an evaluation of an online training and randomized into an intervention or control condition. Baseline and end-of-summer online instruments assessed acceptability, knowledge, and self-reported attitudes and behaviors. One-hundred and forty participants (mean age 17.9 years) completed the study. The innovative training was feasible and acceptable to participants and the organization. Durable increases in safety and health knowledge were achieved by intervention workers (p < 0.001, effect size (Cohen's d) 0.4). However, self-reported safety and health attitudes did not improve with this one-time training. These results indicate the potential utility of online training for younger workers and underscore the limitations of a single training interaction to change behaviors. Interventions may need to be delivered over a longer period of time and/or include environmental components to effectively alter behavior.

Addressing Younger Workers’ Needs: The Promoting U through Safety and Health (PUSH) Trial Outcomes

PubMed Central

Rohlman, Diane S.; Parish, Megan; Elliot, Diane L.; Hanson, Ginger; Perrin, Nancy

2016-01-01

Most younger workers, less than 25 years old, receive no training in worker safety. We report the feasibility and outcomes of a randomized controlled trial of an electronically delivered safety and health curriculum for younger workers entitled, PUSH (Promoting U through Safety and Health). All younger workers (14–24 years old) hired for summer work at a large parks and recreation organization were invited to participate in an evaluation of an online training and randomized into an intervention or control condition. Baseline and end-of-summer online instruments assessed acceptability, knowledge, and self-reported attitudes and behaviors. One-hundred and forty participants (mean age 17.9 years) completed the study. The innovative training was feasible and acceptable to participants and the organization. Durable increases in safety and health knowledge were achieved by intervention workers (p < 0.001, effect size (Cohen’s d) 0.4). However, self-reported safety and health attitudes did not improve with this one-time training. These results indicate the potential utility of online training for younger workers and underscore the limitations of a single training interaction to change behaviors. Interventions may need to be delivered over a longer period of time and/or include environmental components to effectively alter behavior. PMID:27517968

A combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus at 3, 5 and 11 months of age: results of an open, randomized, controlled study.

PubMed

Vesikari, Timo; Forstén, Aino; Desole, Maria Guiseppina; Ferrera, Giuseppe; Caubet, Magalie; Mesaros, Narcisa; Boutriau, Dominique

2013-05-01

This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

[Curcumine (Turmeric - Curcuma longa) as a Supportive Phytotherapeutic Treatment in Oncology].

PubMed

Frassová, Z; Rudá-Kučerová, J

2017-01-01

Turmeric (Curcuma longa) is mainly known as a constituent of curry spice. The main active ingredient, responsible for most of its biological effects, is the polyphenol curcumin. This review aims to provide a comprehensive overview of studies evaluating the benefits of therapeutic curcumin use in oncology. Preclinical studies provide information on the mechanism of action and potential toxicity of curcumin. Clinical studies have so far focused mainly on safety, pharmacokinetics, and determination of the optimal dose of curcumin. However, there are a growing number of trials evaluating the anti-tumor and oncopreventive effects of curcumin and its effect in alleviating the adverse effects of chemotherapeutics and radiotherapy. So far, the results have been optimistic and should encourage further research. The main problem associated with curcumin treatment is its low oral bioavailability, which means it must administrated at high doses to be effective. Therefore, curcumin is more appropriate as a local treatment for areas such as the intestine, mucous membrane, or the skin, where there is no need for a strong systemic effect. Curcumin has a good safety profile when used up to several grams. Curcumin can also be used as a food supplement for people at increased risk of oncological disease, such as heavy smokers or those with pre-cancerous lesions. Due to its good safety profile, curcumin can be recommended to oncological patients who request a natural treatment.Key words: phytotherapy - drug-herb interactions - cancer - adverse effects - curcumine - turmeric - Curcuma longaSubmitted: 20. 7. 2017Accepted: 25. 9. 2017 This publication was written at Masaryk University as part of the project "Behavioural psychopharmacology and pharmacokinetics in preclinical drug research", number MUNI/A/1132/2017 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2018. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects.

PubMed

Oh, Minkyung; Ghim, Jong-Lyul; Park, Sung-Eun; Kim, Eun-Young; Shin, Jae-Gook

2018-01-01

The aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects. This was an open-label, randomized, three-sequence, three-period replicated crossover study in healthy male subjects. The replicated crossover design was done because of high coefficient of variation of PK parameter for fimasartan, that is, >30%. With a 14 days washout period, an FDC tablet containing 60 mg fimasartan, 10 mg amlodipine, and 20 mg rosuvastatin was administered only once, and separate formulations of fimasartan/amlodipine 60 mg/10 mg FDC tablet and 20 mg rosuvastatin tablet administered twice. Blood samples were collected up to 72 hours following drug administration. The plasma concentrations of fimasartan, amlodipine, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was assessed by evaluating vital signs, clinical laboratory parameters, physical examinations, and medical interviews. The geometric mean ratios and 90% confidence intervals (CIs) for the maximum plasma concentration (C max ) and area under the curve from time zero to the last measurable sampling time (AUC t ) were 1.0776 (0.9201-1.2622) and 0.9978 (0.9538-1.0439) for fimasartan, 1.0038 (0.9782-1.0301) and 1.0055 (0.9828-1.0288) for amlodipine, and 1.0006 (0.9290-1.0776) and 0.9986 (0.9532-1.0461) for rosuvastatin, respectively. A total of 22 adverse events (AEs) were reported by 60 subjects; there were no significant differences in the incidence of AEs between the two groups. The 90% CI of the C max of fimasartan was within the widened acceptance limit, ln(0.6984)-ln(1.4319). The 90% CIs of the other PK parameters for drugs were between ln(0.8) and ln(1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile, to the co-administration of its three constituent drugs.

Validation of the French version of the Hospital Survey on Patient Safety Culture questionnaire.

PubMed

Occelli, P; Quenon, J-L; Kret, M; Domecq, S; Delaperche, F; Claverie, O; Castets-Fontaine, B; Amalberti, R; Auroy, Y; Parneix, P; Michel, P

2013-09-01

To assess the psychometric properties of the French version of the Hospital Survey on Patient Safety Culture questionnaire (HSOPSC) and study the hierarchical structure of the measured dimensions. Cross-sectional survey of the safety culture. 18 acute care units of seven hospitals in South-western France. Full- and part-time healthcare providers who worked in the units. None. Item responses measured with 5-point agreement or frequency scales. Data analyses A principal component analysis was used to identify the emerging components. Two structural equation modeling methods [LInear Structural RELations (LISREL) and Partial Least Square (PLS)] were used to verify the model and to study the relative importance of the dimensions. Internal consistency of the retained dimensions was studied. A test-retest was performed to assess reproducibility of the items. Overall response rate was 77% (n = 401). A structure in 40 items grouped in 10 dimensions was proposed. The LISREL approach showed acceptable data fit of the proposed structure. The PLS approach indicated that three dimensions had the most impact on the safety culture: 'Supervisor/manager expectations & actions promoting safety' 'Organizational learning-continuous improvement' and 'Overall perceptions of safety'. Internal consistency was above 0.70 for six dimensions. Reproducibility was considered good for four items. The French HSOPSC questionnaire showed acceptable psychometric properties. Classification of the dimensions should guide future development of safety culture improving action plans.

Profile preferences of Korean American orthodontic patients and orthodontists.

PubMed

Park, Yoon S; Evans, Carla A; Viana, Grace; Anderson, Nina K; Giddon, Donald B

2006-01-01

The purpose of this study was to determine differences in preference for Korean American facial profiles among Korean American orthodontic patients with 2 levels of acculturation, Asian American orthodontists, and Caucasian orthodontists. Images of 1 male and 1 female Korean American adult were animated to move parts of the faces from an extreme retrusive position to an extreme protrusive position by using the Perceptometrics computer program. Three movies were created of the nose, lips, and chin for each image. Three groups of judges, ie, 18 Korean American orthodontic patients, 17 Asian orthodontists, and 18 Caucasian orthodontists selected the most pleasing position and the zone of acceptability as a measure of tolerance. Statistically significant differences were found between Caucasian orthodontists and Korean American orthodontic patients for the most pleasing and midpoint of acceptability positions of female nose and male chin, with no differences in the zone of acceptability position among the groups. In general, the Korean American orthodontic patients preferred a more protrusive nose on the female image and more retrusive chin on the male image than Caucasian orthodontists for the most pleasing and midpoint of acceptability positions, with similar zone of acceptability for all 3 groups.

Consumer acceptance of ozone-treated whole shell eggs.

PubMed

Kamotani, Setsuko; Hooker, Neal; Smith, Stephanie; Lee, Ken

2010-03-01

Ozone-based processing is a novel technology with potentially fewer adverse effects than in-shell thermal pasteurization of eggs. There are no consumer acceptance studies published on ozone-treated eggs. This study examines consumers' ability to detect changes between ozone-treated, thermal-treated, and fresh untreated eggs. Consumers (n = 111) evaluated visual attributes of uncooked eggs and a separate group of consumers (n = 132) evaluated acceptability of cooked eggs. Consumers evaluated attribute intensity of the eggs. The yolks and albumens of the thermal-treated and ozone-treated eggs were perceived to be significantly cloudier than the untreated control, while the ozone-treated eggs were more similar to control (P < 0.05). The yolks of ozone-treated eggs were perceived to have significantly lower heights and greater spreads than the others (P < 0.05). Despite these perceptions, overall visual appeal of ozone-treated eggs was not significantly different from control eggs. A separate set of consumers used hedonic scales to evaluate overall liking, appearance, aroma, flavor, and texture of cooked eggs. Just-about-right (JAR) scales were used to rate the color, moistness, and texture. There were no differences on any attribute scores between the treatments, except thermal-treated and ozone-treated were perceived as less moist than the control. There were no adverse effects on consumer acceptance of eggs, treated with ozone, with acceptance the same as an untreated control. These findings are useful as ozone pasteurization can enhance the safety of fresh shell eggs to meet the goals of the U.S. Egg Safety Action Plan. The U.S. Egg Safety Action Plan requires all shell eggs to be pasteurized to prevent foodborne illness. Heat pasteurization partially cooks the egg, so an alternative process uses ozone with less heat. This study shows the ozone pasteurization has no detectable sensory defects.

Precooked bran-enriched wheat flour using extrusion: dietary fiber profile and sensory characteristics.

PubMed

Gajula, H; Alavi, S; Adhikari, K; Herald, T

2008-05-01

The effect of precooking by extrusion processing on the dietary fiber profile of wheat flour substituted with 0%, 10%, 20%, and 30% wheat bran was evaluated. Depending on the level of bran, total dietary fiber (TDF) and soluble dietary fiber (SDF) in uncooked flours ranged from 4.2% to 17.2% and 1.5% to 2.4%, respectively. Precooking by extrusion significantly increased SDF in flours (by 22% to 73%); although in most cases it also led to a significant decrease in TDF. Cookies and tortillas produced from uncooked and precooked flours with 0% and 20% substituted bran were evaluated for consumer acceptability using a 9-point hedonic scale. With a few exceptions, all cookies had scores ranging from 6 to 7 ("like slightly" to "like moderately") for each attribute, including overall acceptability, appearance, texture, crumbliness, and flavor. Tortillas were rated for the same attributes except for crumbliness, which was replaced with chewiness. In most cases, tortilla scores ranged from 5 to 7 ("neither like nor dislike" to "like moderately"). Consumer acceptability scores of cookies from uncooked flour did not change significantly with increase in bran substitution from 0% to 20%. However, consumer scores for tortillas did decrease significantly with increase in bran level. Extrusion precooking of the flours did not improve the consumer acceptability of cookies and tortillas; however, it did improve their dietary fiber profile by increasing the SDF significantly.

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.

Meeting the requirements of importing countries: practice and policy for on-farm approaches to food safety.

PubMed

Dagg, P J; Butler, R J; Murray, J G; Biddle, R R

2006-08-01

In light of the increasing consumer demand for safe, high-quality food and recent public health concerns about food-borne illness, governments and agricultural industries are under pressure to provide comprehensive food safety policies and programmes consistent with international best practice. Countries that export food commodities derived from livestock must meet both the requirements of the importing country and domestic standards. It is internationally accepted that end-product quality control, and similar methods aimed at ensuring food safety, cannot adequately ensure the safety of the final product. To achieve an acceptable level of food safety, governments and the agricultural industry must work collaboratively to provide quality assurance systems, based on sound risk management principles, throughout the food supply chain. Quality assurance systems on livestock farms, as in other parts of the food supply chain, should address food safety using hazard analysis critical control point principles. These systems should target areas including biosecurity, disease monitoring and reporting, feedstuff safety, the safe use of agricultural and veterinary chemicals, the control of potential food-borne pathogens and traceability. They should also be supported by accredited training programmes, which award certification on completion, and auditing programmes to ensure that both local and internationally recognised guidelines and standards continue to be met. This paper discusses the development of policies for on-farm food safety measures and their practical implementation in the context of quality assurance programmes, using the Australian beef industry as a case study.

Multi-discipline Waste Acceptance Process at the Nevada National Security Site - 13573

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

Carilli, Jhon T.; Krenzien, Susan K.

2013-07-01

The Nevada National Security Site low-level radioactive waste disposal facility acceptance process requires multiple disciplines to ensure the protection of workers, the public, and the environment. These disciplines, which include waste acceptance, nuclear criticality, safety, permitting, operations, and performance assessment, combine into the overall waste acceptance process to assess low-level radioactive waste streams for disposal at the Area 5 Radioactive Waste Management Site. Four waste streams recently highlighted the integration of these disciplines: the Oak Ridge Radioisotope Thermoelectric Generators and Consolidated Edison Uranium Solidification Project material, West Valley Melter, and classified waste. (authors)

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

Inspection Score and Grading System for Food Services in Brazil: The Results of a Food Safety Strategy to Reduce the Risk of Foodborne Diseases during the 2014 FIFA World Cup.

PubMed

da Cunha, Diogo T; Saccol, Ana L de Freitas; Tondo, Eduardo C; de Oliveira, Ana B A; Ginani, Veronica C; Araújo, Carolina V; Lima, Thalita A S; de Castro, Angela K F; Stedefeldt, Elke

2016-01-01

In 2014, Brazil hosted one of the most popular sport competitions in the world, the FIFA World Cup. Concerned about the intense migration of tourists, the Brazilian government decided to deploy a food safety strategy based on inspection scores and a grading system applied to food services. The present study aimed to evaluate the results of the food safety strategy deployed during the 2014 FIFA World Cup in Brazil. To assess food safety, an evaluation instrument was applied twice in 1927 food service establishments from 26 cities before the start of the competition. This instrument generated a food safety score for each establishment that ranged from 0.0 (no flaws observed) to 2565.95, with four possible grades: A (0.0-13.2); B (13.3-502.6); C (502.7-1152.2); and pending (more than 1152.3). Each food service received a stamp with the grade of the second evaluation. After the end of the World Cup, a study was conducted with different groups of the public to evaluate the acceptance of the strategy. To this end, 221 consumers, 998 food service owners or managers, 150 health surveillance auditors, and 27 health surveillance coordinators were enrolled. These participants completed a survey with positive and negative responses about the inspection score system through a 5-point Likert scale. A reduction in violation scores from 393.1 to 224.4 (p < 0.001) was observed between the first and second evaluation cycles. Of the food services evaluated, 38.7% received the A stamp, 41.4% the B stamp, and 13.9% the C stamp. All positive responses on "system reliability" presented a mean of 4.0 or more, indicating that the public believed this strategy is reliable for communicating risks and promoting food safety. The strategy showed positive results regarding food safety and public acceptance. The deployed strategy promoted improvements in the food safety of food services. The implementation of a permanent policy may be well accepted by the public and may greatly contribute to a reduction in foodborne diseases (FBDs).

Profiling contextual factors which influence safety in heavy vehicle industries.

PubMed

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

2014-12-01

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

Organizing uninsured safety-net access to specialist physician services.

PubMed

Hall, Mark A

2013-05-01

Arranging referrals for specialist services is often the greatest difficulty that safety-net access programs face in attempting to provide fairly comprehensive services for the uninsured. When office-based community specialists are asked to care for uninsured patients, they cite the following barriers: difficulty determining which patients merit charity care, having to arrange for services patients need from other providers, and concerns about liability for providing inadequate care. Solutions to these barriers to specialist access can be found in the same institutional arrangements that support primary care and hospital services for the uninsured. These safety-net organization structures can be extended to include specialist physician care by funding community health centers to contract for specialist referrals, using free-standing referral programs to subsidize community specialists who accept uninsured patients at discounted rates, and encouraging hospitals through tax exemption or disproportionate share funding to require specialists on their medical staffs to accept an allocation of uninsured office-based referrals.

Learning Style Profile: Examiner's Manual.

ERIC Educational Resources Information Center

Keefe, James W.; Monk, John S.

This examiner's manual accompanies the Learning Style Profile (LSP), which measures cognitive skills as well as affective and environmental preferences. Charles Letteri's General Operations Model was accepted as the prototype for relating learning styles to cognitive information processing. The LSP was developed from 1983 to 1986; several versions…

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

PubMed

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

2007-01-01

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

Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study.

PubMed

Kowey, Peter R; Crijns, Harry J G M; Aliot, Etienne M; Capucci, Alessandro; Kulakowski, Piotr; Radzik, David; Roy, Denis; Connolly, Stuart J; Hohnloser, Stefan H

2011-12-13

Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo-controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction ≤40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. Celivarone was not effective for the prevention of ICD interventions or sudden death. http://www.clinicaltrials.gov. Unique identifier: NCT00993382.

Effectiveness and safety of ombitasvir, paritaprevir, ritonavir ± dasabuvir ± ribavirin: An early access programme for Spanish patients with genotype 1/4 chronic hepatitis C virus infection.

PubMed

Perelló, C; Carrión, J A; Ruiz-Antorán, B; Crespo, J; Turnes, J; Llaneras, J; Lens, S; Delgado, M; García-Samaniego, J; García-Paredes, F; Fernández, I; Morillas, R M; Rincón, D; Porres, J C; Prieto, M; Lázaro Ríos, M; Fernández-Rodríguez, C; Hermo, J A; Rodríguez, M; Herrero, J I; Ruiz, P; Fernández, J R; Macías, M; Pascasio, J M; Moreno, J M; Serra, M Á; Arenas, J; Real, Y; Jorquera, F; Calleja, J L

2017-03-01

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation. © 2016 John Wiley & Sons Ltd.

Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America.

PubMed

Stadler, Walter M; Figlin, Robert A; McDermott, David F; Dutcher, Janice P; Knox, Jennifer J; Miller, Wilson H; Hainsworth, John D; Henderson, Charles A; George, Jeffrey R; Hajdenberg, Julio; Kindwall-Keller, Tamila L; Ernstoff, Marc S; Drabkin, Harry A; Curti, Brendan D; Chu, Luis; Ryan, Christopher W; Hotte, Sebastien J; Xia, Chenghua; Cupit, Lisa; Bukowski, Ronald M

2010-03-01

The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval. In this nonrandomized, open-label expanded access program, 2504 patients from the United States and Canada were treated with oral sorafenib 400 mg twice daily. Safety and efficacy were explored overall and in subgroups of patients including those with no prior therapy, nonclear cell (nonclear cell) RCC, brain metastases, prior bevacizumab treatment, and elderly patients. Sorafenib was approved for RCC 6 months after study initiation, at which time patients with no prior therapy or with nonclear cell RCC could enroll in an extension protocol for continued assessment for a period of 6 months. The most common grade > or =2 drug-related adverse events were hand-foot skin reaction (18%), rash (14%), hypertension (12%), and fatigue (11%). In the 1891 patients evaluable for response, complete response was observed in 1 patient, partial response in 67 patients (4%), and stable disease for at least 8 weeks in 1511 patients (80%). Median progression-free survival in the extension population was 36 weeks (95% confidence interval [CI], 33-45 weeks; censorship rate, 56%); median overall survival in the entire population was 50 weeks (95% CI, 46-52 weeks; censorship rate, 63%). The efficacy and safety results were similar across the subgroups. Sorafenib 400 mg twice daily demonstrated activity and a clinically acceptable toxicity profile in all patient subsets enrolled in the ARCCS expanded access program (clinicaltrials.gov identifier: NCT00111020).

Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Multiple-Ascending-Dose Study.

PubMed

DeLemos, Byron; Richards, Henry M; Vandenbossche, Joris; Ariyawansa, Jay; Natarajan, Jaya; Alexander, Binu; Ramakrishna, Tage; Murtaugh, Thomas; Stahlberg, Hans-Jürgen

2017-11-01

This randomized, double-blind, parallel-group multiple-ascending-dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUC tau,ss of tramadol increased approximately 2.2- and 3.6-fold for the (+) enantiomer and 2.0- and 3.5-fold for the (-) enantiomer with increasing dose from 200 to 400  and 600 mg/day, whereas the C max,ss increased 2.1- and 3.3-fold for the (+) enantiomer and 2.0- and 3.2-fold for the (-) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment-emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study. © 2017, The American College of Clinical Pharmacology.

An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch.

PubMed

Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li

2017-01-01

We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet ® ) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration ( C max ), extended time to reach the C max and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.

Treatment of facial telangiectasias with a diode-pumped Nd:YAG laser at 532 nm.

PubMed

Cassuto, D A; Ancona, D M; Emanuelli, G

2000-09-01

Facial telangiectasias are a common cause of cosmetic concern. Current treatment modalities present various untoward effects and limits. The pulsed dye laser has been considered the gold standard in efficacy and safety; unfortunately it causes postoperative intracutaneous hematomata, discouraging many patients from undergoing this treatment. Several other vascular lasers (argon, tunable dye, copper, krypton, etc.) are disadvantaged by the risk of hypopigmented and atrophic scars. We assessed a recent powerful version of the potassium titanyl phosphate (KTP) 532 nm laser, which delivers sufficient energy in single pulse lasting 10-50 msec (DioLite 532; IRIDEX, Mountain View, CA, USA). Collateral damage is reduced while the heating of the vessel is slow enough to avoid explosive photothermolysis with its associated purpura. Sixty six patients with facial telangiectasias were treated. In 62/66 patients (93.9%) we achieved a 75-100% clearance of the lesions, while two treatments were needed to reach an acceptable clearance in the remaining 4/66 patients (6.1%). The eventual need for more sessions was well tolerated because the acceptable postoperative appearance allowed patients to continue normal business and social activities between treatments. No permanent complications or undesired effects were noted. We conclude that this diode-pumped frequency-doubled Nd:YAG laser is an effective device for the treatment of facial telangiectasias, with a low profile of undesired effects that can be well tolerated by patients.

One-per-mil tumescent technique for upper extremity surgeries: broadening the indication.

PubMed

Prasetyono, Theddeus O H; Biben, Johannes A

2014-01-01

We studied the effect of 1:1,000,000 epinephrine concentration (1 per mil) to attain a bloodless operative field in hand and upper extremity surgery and to explore its effectiveness and safety profile. This retrospective observational study enrolled 45 consecutive patients with 63 operative fields consisting of various hand and upper extremity problems. One-per-mil solution was injected into the operative field with tumescent technique to create a bloodless operating field without tourniquet. The solution was formulated by adding a 1:1,000,000 concentration of epinephrine and 100 mg of lidocaine into saline solution to form 50 mL of tumescent solution. Observation was performed on the clarity of the operative field, which we described as totally bloodless, minimal bleeding, acceptable bleeding, or bloody. The volume of tumescent solution injected, duration of surgery, and surgical outcome were also reviewed. The tumescent technique with 1-per-mil solution achieved 29% totally bloodless, 48% minimal bleeding, 22% acceptable bleeding, and 2% bloody operative fields in cases that included burn contracture and congenital hand and upper extremity surgeries. One-per-mil tumescent solution created a clear operative field in hand and upper extremity surgery. It proved safe and effective for a wide range of indications. Therapeutic IV. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Current and future role of voluntary surgical contraception in increasing access to and utilization of family planning services in Africa.

PubMed

Gaym, Asheber

2012-10-01

Voluntary surgical contraception is the most widely utilized method of contraception in the world. High effectiveness, low complication rates and reduced cost in the long term make them the ideal contraceptive choice to diverse group of clients including clients from low resource settings. To assess the current status of utilization and effectiveness of voluntary surgical contraception in Africa and suggest possible future roles in contraceptive method choice. A review of available literature on voluntary surgical contraception and synthesis of information under relevant headings. Despite very high total fertility rates in most countries of Africa, surgical contraceptives still contribute to a very small proportion ofcontraceptive method choice in the continent. Client profile and acceptability studies indicate a large unmet need for permanent contraception in the continent. Lack of information, misconceptions and weak health systems (particularly surgical care) are the major impediments to increasing availability of surgical contraception. Lack of knowledge and low levels of motivation among health care providers may also be significant barriers to access. Ihcreasing availability of information on the safety and effectiveness of these methods to both health care providers and the general population can increase demand and acceptability. Delegating service provision to appropriately trained non-physician providers at primary care settings can assist in increasing accessibility of these important family planning methods.

Probabilistic Requirements (Partial) Verification Methods Best Practices Improvement. Variables Acceptance Sampling Calculators: Derivations and Verification of Plans. Volume 1

NASA Technical Reports Server (NTRS)

Johnson, Kenneth L.; White, K, Preston, Jr.

2012-01-01

The NASA Engineering and Safety Center was requested to improve on the Best Practices document produced for the NESC assessment, Verification of Probabilistic Requirements for the Constellation Program, by giving a recommended procedure for using acceptance sampling by variables techniques. This recommended procedure would be used as an alternative to the potentially resource-intensive acceptance sampling by attributes method given in the document. This document contains the outcome of the assessment.

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.

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

Project Gel a Randomized Rectal Microbicide Safety and Acceptability Study in Young Men and Transgender Women

PubMed Central

Cranston, Ross D.; Mayer, Kenneth H.; Febo, Irma; Duffill, Kathryn; Siegel, Aaron; Engstrom, Jarret C.; Nikiforov, Alexyi; Park, Seo-Young; Brand, Rhonda M.; Jacobson, Cindy; Giguere, Rebecca; Dolezal, Curtis; Frasca, Timothy; Leu, Cheng-Shiun; Schwartz, Jill L.; Carballo-Diéguez, Alex

2016-01-01

Objectives The purpose of Project Gel was to determine the safety and acceptability of rectal microbicides in young men who have sex with men (MSM) and transgender women (TGW) at risk of HIV infection. Methods MSM and TGW aged 18–30 years were enrolled at three sites; Pittsburgh, PA; Boston, MA; and San Juan, PR. Stage 1A was a cross-sectional assessment of sexual health and behavior in MSM and TGW. A subset of participants from Stage 1A were then enrolled in Stage 1B, a 12-week evaluation of the safety and acceptability of a placebo rectal gel. This was followed by the final phase of the study (Stage 2) in which a subset of participants from Stage 1B were enrolled into a Phase 1 rectal safety and acceptability evaluation of tenofovir (TFV) 1% gel. Results 248 participants were enrolled into Stage 1A. Participants’ average age was 23.3 years. The most common sexually transmitted infection (STIs) at baseline were Herpes simplex (HSV)-2 (16.1% by serology) and rectal Chlamydia trachomatis (CT) (10.1% by NAAT). 134 participants were enrolled into Stage 1B. During the 12 week period of follow-up 2 HIV, 5 rectal CT, and 5 rectal Neisseria gonorrhea infections were detected. The majority of adverse events (AEs) were infections (N = 56) or gastrointestinal (N = 46) and were mild (69.6%) or moderate (28.0%). Of the participants who completed Stage 1B, 24 were enrolled into Stage 2 and randomized (1:1) to receive TFV or placebo gel. All participants completed Stage 2. The majority of AEs were gastrointestinal (N = 10) and of mild (87.2%) or moderate (10.3%) severity. Conclusions In this study we were able to enroll a sexually active population of young MSM and TGW who were willing to use rectal microbicides. TFV gel was safe and acceptable and should be further developed as an alternative HIV prevention intervention for this population. Trial Registration ClinicalTrials.gov NCT01283360 PMID:27362788

Driver acceptance of commercial vehicle operations (CVO) technology in the motor carrier environment. Executive summary, Critical issues relating to acceptance of technology by interstate truck and bus drivers

DOT National Transportation Integrated Search

2000-05-01

The California database incorporated in the Highway Safety Information System (HSIS) is derived from the California TASAS (Traffic Accident Surveillance and Analysis System). The system, maintained by the Traffic Operations Office of Caltrans, is a m...

INPRO Assessment of an INS in the Area of Safety of Fuel Cycle Installations

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

Raj, B.; Busurin, Y.; Depisch, F.

2006-07-01

INPRO has defined requirements organized in a hierarchy of Basic Principles, User Requirements and Criteria (consisting of an indicator and an acceptance limit) to be met by innovative nuclear reactor systems (INS) in six areas, namely: economics, safety, waste management, environment, proliferation resistance, and infrastructure. If an INS meets all requirements in all areas it represents a sustainable system for the supply of energy, capable of making a significant contribution to meeting the energy needs of the 21. century. Draft manuals have been developed, for each INPRO area, to provide guidance for performing an assessment of whether an INS meetsmore » the INPRO requirements in a given area. The manuals set out the information that needs to be assembled to perform an assessment and provide guidance on selecting the acceptance limits and, for a given INS, for determining the value of the indicators for comparison with the associated acceptance limits. Each manual also includes an example of a specific assessment to illustrate the guidance. This paper discusses the manual for performing an INPRO assessment in the area of safety of fuel cycle installations. The example, chosen solely for the purpose of illustrating the INPRO methodology, describes an assessment of an MOX fuel fabrication plant based on sol-gel technology and illustrates an assessment performed for an INS at an early stage of development. The safety issues and the assessment steps are presented in detail in the paper. (authors)« less

Evaluation of facial attractiveness in black people according to the subjective facial analysis criteria.

PubMed

Melo, Andréa Reis de; Conti, Ana Cláudia de Castro Ferreira; Almeida-Pedrin, Renata Rodrigues; Didier, Victor; Valarelli, Danilo Pinelli; Capelozza Filho, Leopoldino

2017-02-01

The objective of this study was to evaluate the facial attractiveness in 30 black individuals, according to the Subjective Facial Analysis criteria. Frontal and profile view photographs of 30 black individuals were evaluated for facial attractiveness and classified as esthetically unpleasant, acceptable, or pleasant by 50 evaluators: the 30 individuals from the sample, 10 orthodontists, and 10 laymen. Besides assessing the facial attractiveness, the evaluators had to identify the structures responsible for the classification as unpleasant and pleasant. Intraexaminer agreement was assessed by using Spearman's correlation, correlation within each category using Kendall concordance coefficient, and correlation between the 3 categories using chi-square test and proportions. Most of the frontal (53. 5%) and profile view (54. 9%) photographs were classified as esthetically acceptable. The structures most identified as esthetically unpleasant were the mouth, lips, and face, in the frontal view; and nose and chin in the profile view. The structures most identified as esthetically pleasant were harmony, face, and mouth, in the frontal view; and harmony and nose in the profile view. The ratings by the examiners in the sample and laymen groups showed statistically significant correlation in both views. The orthodontists agreed with the laymen on the evaluation of the frontal view and disagreed on profile view, especially regarding whether the images were esthetically unpleasant or acceptable. Based on these results, the evaluation of facial attractiveness according to the Subjective Facial Analysis criteria proved to be applicable and to have a subjective influence; therefore, it is suggested that the patient's opinion regarding the facial esthetics should be considered in orthodontic treatmentplanning.

Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies.

PubMed

Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

2014-10-01

Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

Vaccination Against Dengue: Challenges and Current Developments.

PubMed

Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

2016-01-01

Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients

PubMed Central

Huang, Qi-Fang; Li, Yan; Wang, Ji-Guang

2014-01-01

We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug. PMID:24403822

Role of natural herbs in the treatment of hypertension

PubMed Central

Tabassum, Nahida; Ahmad, Feroz

2011-01-01

Hypertension (HTN) is the medical term for high blood pressure. It is dangerous because it makes the heart work too hard and contributes to atherosclerosis (hardening of arteries), besides increasing the risk of heart disease and stroke. HTN can also lead to other conditions such as congestive heart failure, kidney disease, and blindness. Conventional antihypertensives are usually associated with many side effects. About 75 to 80% of the world population use herbal medicines, mainly in developing countries, for primary health care because of their better acceptability with human body and lesser side effects. In the last three decades, a lot of concerted efforts have been channeled into researching the local plants with hypotensive and antihypertensive therapeutic values. The hypotensive and antihypertensive effects of some of these medicinal plants have been validated and others disproved. However, ayurvedic knowledge needs to be coupled with modern medicine and more scientific research needs to be done to verify the effectiveness, and elucidate the safety profile of such herbal remedies for their antihypertensive potential. PMID:22096316

76 FR 53494 - In the Matter of United States Enrichment Corporation; Paducah Gaseous Enrichment Plant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... removable contamination, unless otherwise authorized by Health Physics. USEC- Paducah is required by... Section V are acceptable and necessary and conclude that with these commitments the public health and safety are reasonably assured. In view of the foregoing, I have determined that public health and safety...

76 FR 17487 - Protection of Stratospheric Ozone: New Substitute in the Motor Vehicle Air Conditioning Sector...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-29

... and to disapprove substitutes that present overall risks to human health and the environment more.... Acceptability Decision B. Use Conditions C. Environmental Impacts D. Health and Safety Impacts E. Retrofit Usage...: Protection of Children From Environmental Health and Safety Risks H. Executive Order 13211: Actions That...

14 CFR 415.129 - Flight safety system test data.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., acceptance, age surveillance, and preflight testing of a flight safety system and its subsystems and..., subsystem, and component testing requirements of part 417 of this chapter and appendix E to part 417 of this... demonstrate similarity by performing the analysis required by appendix E of part 417 of this chapter. The...

14 CFR 415.129 - Flight safety system test data.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., acceptance, age surveillance, and preflight testing of a flight safety system and its subsystems and..., subsystem, and component testing requirements of part 417 of this chapter and appendix E to part 417 of this... demonstrate similarity by performing the analysis required by appendix E of part 417 of this chapter. The...

14 CFR 415.129 - Flight safety system test data.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., acceptance, age surveillance, and preflight testing of a flight safety system and its subsystems and..., subsystem, and component testing requirements of part 417 of this chapter and appendix E to part 417 of this... demonstrate similarity by performing the analysis required by appendix E of part 417 of this chapter. The...

14 CFR 415.129 - Flight safety system test data.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., acceptance, age surveillance, and preflight testing of a flight safety system and its subsystems and..., subsystem, and component testing requirements of part 417 of this chapter and appendix E to part 417 of this... demonstrate similarity by performing the analysis required by appendix E of part 417 of this chapter. The...

14 CFR 415.129 - Flight safety system test data.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., acceptance, age surveillance, and preflight testing of a flight safety system and its subsystems and..., subsystem, and component testing requirements of part 417 of this chapter and appendix E to part 417 of this... demonstrate similarity by performing the analysis required by appendix E of part 417 of this chapter. The...

75 FR 9196 - Letter From Secretary of Energy Accepting Defense Nuclear Facilities Safety Board (Board...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... capability for non- vital laboratory room electrical loads that provides an engineered control to reduce..., approximately two orders of magnitude higher than our evaluation guideline for selecting safety class controls. Approval of the DSA included recognition of weaknesses in the facility's control set and the need to...

Food safety education using an interactive multimedia kiosk in a WIC setting: correlates of client satisfaction and practical issues.

PubMed

Trepka, Mary Jo; Newman, Frederick L; Huffman, Fatma G; Dixon, Zisca

2010-01-01

To assess acceptability of food safety education delivered by interactive multimedia (IMM) in a Supplemental Nutrition Program for Women, Infants and Children Program (WIC) clinic. Female clients or caregivers (n=176) completed the food-handling survey; then an IMM food safety education program on a computer kiosk. Satisfaction with program, participant demographics, and change in food-handling behavior were assessed by univariate analyses. Over 90% of the participants enjoyed the kiosk, and most (87.5%) reported using computers a lot. Compared with participants with education beyond high school, participants with less education were more likely to report enjoying the kiosk (98.2% vs 88.1%, P = .007), preferred learning with the kiosk (91.7% vs 79.1%, P = .02), and would like to learn about other topics using IMM (95.4% vs 86.6%, P = .04). Food safety education delivered by IMM was well accepted by inner-city WIC clinic clients, including those with less education. Copyright 2010 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

Guideline for the utilization of commercial grade items in nuclear safety related applications: Final report. [Contains Glossary

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

Tulay, M.P.; Yurich, F.J.; Schremser, F.M. Jr.

1988-06-01

This guideline provides direction for the procurement and use of Commercial Grade Items (CGI)in safety-related applications. It is divided into five major sections. A glossary of terms and definitions, an acronym listing, and seven appendices have been included. The glossary defines terms used in this guideline. In certain instances, the definitions may be unique to this guideline. Identification of acronyms utilized in this guideline is also provided. Section 1 provides a background of the commercial grade item issues facing the nuclear industry. It provides a historical perspective of commercial grade item issues. Section 2 discusses the generic process for themore » acceptance of a commercial grade item for safety-related use. Section 3 defines the four distinct methods used to accept commercial grade items for safety-related applications. Section 4 lists specific references that are identified in this guideline. Section 5 is a bibliography of documents that were considered in developed this guideline, but were not directly referenced in the document.« less

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)

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.

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

PubMed

Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M

2014-02-12

The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reduced fat and sugar vanilla ice creams: sensory profiling and external preference mapping.

PubMed

Cadena, R S; Cruz, A G; Faria, J A F; Bolini, H M A

2012-09-01

The aims of this study were (1) to map sensory attributes of vanilla ice cream with reduced fat and sugar, and (2) to determine drivers of liking by applying external preference mapping and reveal the relationship between descriptive attributes and hedonic judgments using the partial least squares method. Descriptive sensory profiles (n=11) and consumer test (n=117) of 6 samples of vanilla ice cream (3 traditional and 3 with reduced fat and sugar) were determined. The attributes brightness and sweet aftertaste for sample and creaminess (appearance and texture) and sweet aroma contributed positively to the acceptance of ice cream samples. The attributes aeration, powdered milk aroma and flavor, and white chocolate aroma and flavor contributed positively to the acceptance of the ice creams. The attributes hydrogenated fat aroma and flavor were responsible for the lower acceptance of samples. The reduction in fat and sugar did not necessarily cause a decrease in acceptance. The most important factors were selection of the appropriate sweetener system and the use of good quality raw material. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.